Viral Hepatitis Poster Session – Monday Nov 3: 8 AM

 

HCV Treatment - PegIntron

 

1216. Impact of Advanced Fibrosis and Cirrhosis on Sustained Virologic Response of HCV G1-Infected Patients: Results of The Canadian POWeR Program. 

P. Marotta; C. Cooper; D. K. Wong; J. Farley; M. Elkashab; K. M. Peltekian; N. Abadir; R. N. Woolstencroft; R. J. Bailey

 

Purpose:

To evaluate the impact of advanced fibrosis/cirrhosis on SVR rates in treatment-naive Genotype 1-infected chronic hepatitis C patients treated with weight-based PEG-IFN alfa-2b and weight-based ribavirin (RBV) in “real-life” clinical settings.

 

Methods:

The POWeR program was a prospective, non-interventional observational study conducted at 138 community and academic centers in Canada. HCV genotype 1 (G1)-infected patients were treated for up to 48 weeks with PEG-IFN alfa-2b (1.5μg/kg/wk) plus weight-based RBV (800–1200 mg/d). This ITT analysis focuses on G1 patients who provided a liver biopsy specimen (assigned Metavir score of F1 to F4) and received at least one treatment dose; HIV/HCV co-infected patients were excluded. SVR was defined as undetectable HCV RNA 24 weeks post-treatment. Baseline viral load results were included, where available. Statistical analysis was performed with Fisher’s Exact test.

 

Results:  

This ITT analysis involved 718 G1-infected patients with liver biopsy specimens, with mild-to-moderate fibrosis (F1-F2) in 60% (432/718) and advanced fibrosis/cirrhosis (F3-F4) in 40% (286/718). Baseline viral load results were available for 651/718 (91%) patients, revealing high viral load (HVL, >600,000 IU/mL) in 356/651 (55%).

 

Overall SVR amongst patients with liver biopsy was 38% (272/718). SVR in patients with F1, F2, F3 and F4 fibrosis was 52%, 46%, 26% and 18%, respectively. End-of-treatment (EOT) responses were significantly higher in patients with F1-F2 fibrosis than in those with F3-F4 advanced fibrosis/cirrhosis (59% vs 34%, P<.0001); corresponding SVR rates were 48% and 22% (P<.0001). Relapse after EOT response was higher in patients with F3-F4 than F1-F2 fibrosis (35% vs 18%, P=.0009). Patients with F1-F2 fibrosis and low viral load (LVL, ≤600,000 IU/mL; N=172) achieved significantly higher SVR rates than those with F1-F2 and HVL (N=219) (58% vs 41%, P=.0008); however, the effect of HVL on SVR was not apparent amongst patients with F3-F4 advanced fibrosis or cirrhosis (20% LVL vs 21% HVL, P=NS; N=123 and 137, respectively).

 

Conclusions:

Advanced liver disease diminished genotype 1 SVR rates of patients treated with PEG-IFN alfa-2b plus weight-based RBV therapy. Advanced fibrosis/cirrhosis superseded the impact of viral load, as HVL reduced SVR rates in patients with mild/moderate fibrosis but not those with advanced disease. These results suggest genotype 1 patients with F3/F4 fibrosis require additional therapeutic approaches, including modified dose and/or duration of treatment, to optimize outcomes.

 


HCV Treatment – General

 

1220. Anti-viral therapy in haemodialyzed HCV patients: efficacy, tolerance and treatment strategy.  

P. Deltenre; D. Thabut; A. Tran; H. Castel; M. El Nady; V. Canva; A. Louvet; H. Ben Ali; F. Provot; F. Glowacki; S. Dharancy; F. Stanke; J. Henrion; C. Noel; P. Mathurin

 

Introduction:

In haemodialyzed HCV patients (HDP), viral eradication is an attractive option because HCV has a deleterious impact on survival after renal transplantation.

 

Aim:

In this prospective study of HDP treated with PegIFN and ribavirin (RBV) (1000 mg/week), our aims were to:

1.     analyse virological response (VR);

2.     evaluate tolerance and propose a strategy for erythropoietin (EPO) use;

3.     compare RBV concentrations between HDP and HCV controls with normal renal function.

 

Methods and study design:

In the first part of the study, EPO was increased when HB was <10g/dl (strategy 1). As interim analysis observed a drastic increase in EPO need and a high rate of transfusion, a new strategy was defined: EPO was doubled from the start of the treatment and then adapted to HB level (strategy 2). Treatment duration was 6-12 months (M) according to genotype (G).

 

Results:

31 HDP (21 G1/4, 10 G2/3) waiting for renal transplantation were included. Median viral load was 350,000 IU/ml (95%CI: 146,100-2,200,000). Fibrosis was ≤F2 in 27 HDP.

 

Median PegIFNα2a/α2b doses were 150 (95%CI: 135-180) and 50µg/week (95%CI: 35-50). Median RBV dose was 112mg/day (95%CI: 86-142).

 

1. 31% of HDP had rapid VR (G1/4: 17%, G2/3: 62%, p=0.02), 79% early VR (G1/4: 74%, G2/3: 89%, p=0.4), and 48% sustained VR (G1/4: 40%, G2/3: 60%, p=0.3). One HDP died from cerebral haemorrhage unrelated to treatment as HB and platelets were within normal ranges.

 

2. When compared to strategy 1, HDP treated with strategy 2 had higher median EPO doses during M1 (20000 vs. 6000U/week, p=0.0001), higher median HB levels at week 2 (12.7 vs. 11.4mg/dl, p=0.04), M1 (12.8 vs. 11.2, p=0.01), M2 (12.2 vs. 10.0, p=0.01) and M3 (10.8 vs. 9.8, p=0.03). There was a trend for less patients transfused with strategy 2 (18 vs. 40%, p=0.2), and for less packed red blood cells transfused per patient and per month of treatment (0.02 vs. 0.17 p=0.14).

 

3. Median RBV concentrations were not different in HDP and healthy controls from M2-12 (1.2 vs. 2.4mg/l at M2, 2.1 vs. 1.9 at M3, 2.1 vs. 2.4 at M4, 1.5 vs. 2.0 at M5, 2.1 vs. 2.1 at M6, 2.4 vs. 1.8 at M9, and 1.8 vs. 2.6 at M12, all p>0.05). However, time to reach steady-state RBV concentration was longer in HDP than in healthy controls as shown by median RBV concentrations at weeks 2 (0.5 vs. 1.3mg/l, p=0.01) and 4 (0.8 vs. 1.7, p=0.03).

 

Conclusions:

50% of HDP treated with PegIFN and adapted doses of RBV reached sustained VR. The strategy consisting in doubling EPO from the start of the treatment provides better tolerance than adaptation on demand. 5 pills of RBV/week lead to adequate concentrations. However, the delay to reach steady-state concentrations has to be considered to determine the ideal RBV dose in HDP.

 


HCV Treatment – PegIntron

 

1222. Impact of the use of drugs and substitution treatments on the antiviral treatment of chronic hepatitis C (HCV): analysis of compliance, virological response and quality of life (Cheobs). 

P. Melin; J. Lang ; D. Ouzan; M. Chousterman ; M. Varastet; M. Rotily ; T. Fontanges ; P. Marcellin; P. Cacoub

 

Purpose:

Cheobs is a French, multicentric and prospective study which aimed to analyse the factors associated with the compliance with treatment by Peginterferon alpha-2b and Ribavirin in HCV+ patients. The present analysis focuses on the compliance with antiviral dual therapy, the virological response and the quality of life (SF-36) during treatment according to whether the patients were active drug users or under substitution treatment (ADU), ex-drug users (EDU) or non drug users (NDU).

 

Methods:

Between 2003 and 2006, 184 clinicians included 2,001 HCV+ patients, evaluated on Day 0, then every three months (M3, M6, M9, M12) during treatment, and 6 months after end of treatment. Among these 2,001 patients, 141 were excluded from the analysis (prescription of an antiviral single agent therapy, date of the end of treatment or virological response unavailable). The studied population included 1,860 patients : 244 ADU, 578 EDU and 1,038 NDU. Good compliance was defined by >80% of the dose and duration of the antiviral dual therapy prescribed. The sustained virologic response was defined by a negative PCR ≥ 12 weeks after the end of treatment.

 

Results:

The patient profile of the EDU group was between those of the ADU and NDU groups for mean age, BMI, fibrosis stages, % patients with a high level of education, a level of debt difficult to manage, high consumption of alcohol, psychiatric disorders or chronic diseases. Most of the patients were naïve of any antiviral treatment (72.2%), but were more numerous (p<0.001) in the ADU (82.3%) than in the EDU (73.5%) or NDU (69.1%) group. The good compliance of patients with dual therapy was similar in all three groups: NDU 49.4%, EDU 48.6% and ADU 52.2% (p=0.7). The sustained virologic response rate did not differ in the ADU, EDU and NDU groups: 57.8%, 50.9% and 49.3% respectively (p=0.13). The quality of life of patients in the ADU group was less altered on the physical and psychological levels than the patients in the other groups.

 

Conclusion:

The rate of sustained virologic response was similar in the active or substitution drug users and in the ex- or non-users. Excess consumption of alcohol, a precarious socio-economic situation, and the psychiatric diseases observed in drug users in this study did not have a negative impact on the studied factors. On the contrary, young age, recent contamination, high prevalence of genotype 3, lower BMI, less severe stage of fibrosis and good compliance with the treatment seem to have balance the negative parameters.

 


HCV Treatment – PegIntron

 

1224. Extended treatment with peginterferon alfa-2b and ribavirin combination therapy can suppress the relapse rate after treatment of chronic hepatitis C genotype 1 patients with late viral response. 

T. Oze; N. Hiramatsu; T. Yakushijin; M. Kurokawa; T. Igura; K. Mochizuki; K. Imanaka; A. Yamada; M. Oshita; H. Hagiwara; E. Mita; T. Ito; Y. Inui; T. Hijioka; H. Yoshihara; E. Hayashi; A. Inoue; Y. Imai; M. Kato; Y. Yoshida; T. Tatsumi; K. Ohkawa; S. Kiso; T. Kanto; A. Kasahara; S. Tamura; T. Takehara; N. Hayashi

 

Background & Aim:

Chronic hepatitis C genotype 1 patients with late viral response (LVR) to peginterferon (Peg-IFN) alfa-2b and ribavirin (RBV) combination therapy (detectable serum HCV RNA at week 12; undetectable at week 24) show a low SVR rate due to frequent relapse after treatment. We evaluated the efficacy of Peg-IFN alfa-2b and RBV administration for 72 weeks in HCV genotype 1 patients with LVR, compared with that for 48 weeks.

 

Patients & Methods:

This study, conducted at Osaka University Hospital and institutions participating in the Osaka Liver Forum, enrolled 775 patients treated with combination therapy of Peg-IFN alfa-2b and RBV. Among the patients who responded, 48-week treatment was done for 365 with early viral response (undetectable serum HCV RNA at week 12). Among 164 patients with LVR, 86 were treated for 48 weeks (46 males, 40 females, mean age 56.4 ± 9.3 y.o.), and 78 were treated for 72 weeks (33 males, 45 females, mean age 59.5 ± 8.3 y.o.). Relapse was defined as undetectable serum HCV RNA at end of treatment but detectable at 24 weeks after the treatment using the COBAS AMPLICOR HCV test, v2.0 (<50 IU/ml). Drug exposure was calculated as the average dose actually taken during the treatment per body weight.

 

Results:

Among the patients with LVR, the relapse rate with 72-week treatment (37%, 29/78) was lower than that with 48-week treatment (66%, 57/86) (p < 0.001). The relapse rate in aged patients ≥ 65 y.o., which was higher than in younger patients with 48-week treatment (85%, 15/20 vs. 61%, 40/66; p = 0.06) markedly decreased with 72-week treatment (85% vs. 39%, 11/28; p < 0.001). With extended treatment of 72 weeks, the timing of the HCV RNA disappearance showed a strong correlation with relapse. The relapse rate was 16% (6/38) in patients with undetectable HCV RNA at week 16, 53% (10/19) at week 20, 75% (9/12) at week 24 (p < 0.001). Analysis of the relationship of relapse and drug exposure for patients given 72-week treatment showed the relapse rate to be lower in those receiving ≥ 1.0 µg/kg/week of Peg-IFN (Peg-IFN ≥ 1.0 µg/kg/week, 32%, 20/63 vs. Peg-IFN < 1.0 µg/kg/week, 60%, 9/15; p < 0.05), and also for those receiving ≥ 8 mg/kg/day of RBV (RBV ≥ 8 mg/kg/day, 31%, 18/59 vs. RBV < 8 mg/kg/day, 58%, 11/19; p < 0.05).

 

Conclusion:

Extended treatment of Peg-IFN alfa-2b and RBV combination therapy up to 72 weeks significantly suppressed the relapse rate in LVR patients. An earlier response predicts a lower relapse rate in LVR patients given 72-week treatment. Drug exposure to both drugs still affected the viral relapse after the treatment among LVR patients completing 72 weeks of treatment.


HCV Treatment – Pegasys

 

1227. High rates of sustained virological response in HCV-infected injection drug users receiving directly observed therapy with peginterferon alfa-2a and once daily ribavirin.  

M. Waizmann; K. Wolle; F. Ackermann

 

Aim:

To evaluate safety and efficacy of early and directly observed therapy with peginterferon alfa-2a and ribavirin (RBV) in HCV-infected injection drug users (IDUs) linked to a drug treatment program in an outpatient center.

 

Methods:

Retrospective open label study conducted in an outpatient center. Observation and analysis period January 2005 to May 2008.

 

Inclusion criteria:

·                    Treatment-naïve HCV-infected IDUs (≥ 18 years) on stable L-polamidone or buprenorphine treatment.

 

Exclusion criteria:

·                    HIV-coinfection, non-adherence to substitution drug and alcohol treatment, suicidal behaviour. 

 

Directly Observed Therapy:

·                    Patients received directly observed therapy with peginterferon alfa-2a (40KD) 180µg/week plus fixed-dosed RBV (800 mg or 1200 mg according to genotype). RBV was taken once daily as observed therapy concomitantly with L-polamidone (10-50 mg/day) or buprenorphine (0,6 mg-7,4 mg/day). Citalopram (20-40 mg/day) was initiated two weeks prior to starting HCV treatment and continued during the complete course of therapy in all patients.

·                    Treatment duration: 48 weeks in genotype 1/4 and 24 weeks in genotype 2/3 patients. No liver biopsies were conducted. Plasma HCV RNA was quantified by real time PCR. SVR was defined as undetectable HCV RNA (< 50 IU/ml) 24 weeks after end of treatment.

 

Results:

·                    To date, 50 subjects were enrolled, 49 patients were dosed and 48 completed treatment. 1 subject was excluded due to massive concomitant drug abuse prior to start of HCV treatment.

·                    33 males/16 females. Mean age 30.1 years, mean duration of injection drug use 6.4 years, HCV infection known since 3.4 years (mean).

·                     HCV genotype 1 (n=20), genotype 2/3 (n=28), genotype 4 (n=1). Median baseline HCV RNA was 132,465 IU/ml (range 1.407 – 22.146.587).

·                    1 patient (genotype 1) discontinued due to non-response.

·                    Overall SVR rate was 98% (n=45) with 95% (n=20) in genotype 1/4 and 100% in genotype 2/3 patients (n=28). Treatment was well tolerated. No new adverse events were observed other than known adverse events of peginterferon alfa-2a and RBV. No dose adjustment of antiviral drugs was required. Interferon-induced depression required dose adjustment of citalopram in 3 subjects.

 

Conclusions:

·                    Successful treatment of HCV-infected IDUs with peginterferon alfa-2a and RBV can be achieved in an optimal substitution setting.

·                    Directly observed therapy delivering 100% of antiviral dosages and ensuring completion of full length of treatment (100%) resulted in SVR rates of 95% in genotype 1/4 patients and 100% in genotype 2/3 patients.

·                    Once daily observed intake of fixed-dose RBV may have contributed to better adherence and improved outcome.


HCV Treatment – PegIntron

 

1229. Virological Response to Treatment with Pegylated Interferon alfa-2b and ribavirin chronic hepatitis C in Children. 

M. Pawlowska; M. Pilarczyk; W. Halota; E. Jendryczka

 

Introduction:

Treatment of chronic hepatitis C in children with recombinant IFN alpha and ribavirin has efficacy above 50%. The aim of the study was an assessment of the efficacy and safety of treatment of chronic hepatitis c in children with pegylated IFN alpha and ribavirin.

 

Methods:

Investigations were performed in 53 children (16 girls and 37 boys) with chronic hepatitis C in the age 8 – 17 years (mean age 13,6+2,4 years). HCV genotypes were as follow: genotype1 HCV (n=27), genotype 3 HCV (n=2) and genotype 4 (n=24).

 

Mean duration of HCV infection was 8,5 + 4,6 years, main route of HCV transmission were nosocomial infections. Examined children were divided on 2 groups (A and B). Children from group A (n=29) were naïve and they administered combined therapy with pegylated IFN alpha-2b (PegIntron) in the dose 1,5mcg/kg/week and ribavirin 15mg/kg/daily during 48 weeks. Patients from group B (n=24) were treated firstly with recombinant IFN alpha-2b (Intron A) 3MU three times a week and ribavirin 15mg/kg/day during 12 months and as retherapy they administered combined therapy with pegylated IFN alpha-2b (PegIntron) in the dose 1,5mcg/kg/week and ribavirin 15mg/kg/daily during 12 months. Mean baseline viral load was 0,456x10^6 IU/mL, mean ALT activity 45,8+24,3 IU/mL. No child had liver disease assessed as greater than grade 2, stage 2.

 

During the study serum HCV RNA in TW 12 - EVR, TW 48 - ETR and W 72 - SVR) with PCR method (Roche TaqMan) were evaluated.

 

Results:

Sustained viral response achieved in 47% of children (62 % naïve and 33% from group of retherapy). Prevalence of relapses was 7,5%, respectively 5,6% in group A and 33% in group B.

 

The most important predictor of SVR in both groups was undetectable HCV RNA at TW 12 (complete EVR). SVR attained 13/18 of naïve subjects with undetectable HCV RNA at TW 12 and 8/8 retreated. All retreated children who achieved partial EVR were relapsers.

 

In responders from both groups baseline ALT activity was higher and baseline viral load was lower. In all children, who achieved SVR, HCV RNA is undetectable 12 months after.

 

Conclusions.

1.     Pegylated IFN and ribavirin are efficient in treatment of chronic hepatitis C in children.

2.     cEVR is the predictor of sustained viral response.

3.     High rate of relapses in retreated patients may suggest longer duration of retherapy.


HCV Treatment – General

 

1232. Re-infection following successful treatment for Hepatitis C virus Infection. 

J. Farley; Y. Al-Khafaji

 

Introducation

Guidelines for treatment of chronic hepatitis C Virus (HCV) infections in Intravenous Drug Users (IDUs) do not recommend counseling, testing, monitoring, or follow-up beyond six months after End Of Treatment (EOT), despite the concerns about the possibility of reinfection. In this study, we investigated the likelihood of HCV reinfection and the likely mode of transmission.

 

Method:

We reviewed the database of all patients (IDUs and non-IDUs) treated at our clinic between August 1999 and April 2008. We assumed that re-infection happened halfway between the date of the last negative test result and the date of the first subsequent positive test result for HCV.

 

Results:

Of 180 individuals with complete data, we identified 18 IDU patients who were reinfected after successful treatment (HCV RNA was undetectable at least six months after completing the recommended treatment (Sustained Virological Response (SVR)), or if the SVR was not available, a new genotype was identified.). The reinfection rate was 10.6 cases per 100 person-years. The time of occurrence of reinfection had a mean of 72.8 weeks after the scheduled EOT and a standard deviation of 48.9 weeks. The likely causes of reinfection included intravenous drug use, percutaneous contact, and tattooing. Two years ago, we reported seven cases of reinfection; as we continued to monitor over the last two years, 11 new cases have been identified, making it a total of 18 reinfection cases. We feel that this is an underestimated value of the true occurrence of the reinfection as many patients (especially IDUs) have not been coming for regular follow up visits at our clinic.

 

Conclusion:

Overall, we have demonstrated that IDUs can be suscessfully treated for HCV infections; however, reinfection may decrease the effectiveness of such treatment programs.

 

We recommend that any effective treatment program for treating HCV in IDUs must include pre treatment counseling as well as on going follow up and testing after successfully treating the HCV infection. Harm reduction strategies should also be continually reinforced.

 


HCV Treatment – Acute Infection

 

1233. Rapid virologic response is common in acute hepatitis C virus (HCV) infection regardless of genotype.  

C. E. Birch; A. Y. Kim; L. L. Reyor; M. J. Bowen; E. H. Nagami; B. McGovern

 

Background:

Rapid virologic response (RVR) is a strong predictor of a sustained virologic response (SVR) in the treatment of HCV infection. However, RVR is achieved in only a small minority of patients with chronic HCV genotype one infection. We hypothesized that RVR may be higher in the setting of acute infection.

 

Methods:

Two cohorts were examined to determine the proportion of patients who attained RVR in the setting of acute HCV infection. Retrospective chart reviews were conducted in community patients treated at a tertiary care medical center. Patients who did not have HCV RNA testing at four weeks were excluded from analysis. Four week HCV RNA levels were obtained prospectively in a cohort of incarcerated patients undergoing treatment for acute HCV infection in state correctional facilities in Massachusetts. Patients were treated with pegylated interferon and ribavirin for varying durations of time (mean, 19.5 weeks; range 12-48).

 

Results:

Twenty-six patients were analyzed, including 15 men and 11 women; mean age is 32 years (IQR 24-36). Twenty-one were white, two were Hispanic, and three were other. Risk factors included injection drug use (n=21), sexual transmission (n=2), needle stick injury (n=1), and unknown (n=1). Genotype distribution was as follows: genotype one (n=16), genotype 2 (n=3), genotype 3 (n=4), genotype 4 (n=2), and unknown genotype (n=1). RVR was achieved in 25 of 26 patients. SVR was achieved in 15 of 16 patients; two were lost to follow up and final outcomes are pending in the remainder.

 

Conclusions:

In contrast to chronic disease, the proportions of patients who achieve RVR are much higher in the setting of acute HCV infection. Although many of these patients underwent therapy outside the 12-16 week window period traditionally used to treat patients with acute HCV infection, the high rates of RVR suggest that a sustained virologic response may still be achieved, regardless of genotype.

 


HCV Treatment – Pegasys

 

1239. Are there differences in treatment outcomes between HCV genotype 2 and 3 patients with advanced fibrosis treated with peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®)? 

S. Bruno; S. J. Hadziyannis; M. L. Shiffman; D. Messinger; P. Marcellin

 

Background:

It has been previously shown that among patients infected with genotype 2 or 3 HCV treated with pegIFN alfa-2a 180µg/wk plus ribavirin (RBV) 800mg/day, rates of sustained virological response (SVR) are generally higher for G2 and overall 24wks of therapy is better than 16wks. The objective of this retrospective analysis of data from two large international phase III studies, is to extend these analyses to patients with advanced hepatic fibrosis infected with G2/3 treated with pegIFN alfa-2a plus RBV for 16 or 24wks.

 

Methods:

G2/3 patients with advanced fibrosis/cirrhosis included in this analysis were those assigned to 16 or 24wks of treatment with pegIFN alfa-2a 180μg/wk plus RBV 800mg/day. Bridging fibrosis/cirrhosis was defined as metavir 3+4, Knodell 3+4, Ishak 4+5+6 on the pre-treatment liver biopsy. Responses were defined as rapid virological response (RVR;HCV RNA <50IU/mL at wk4), complete early virological response (EVR) (non-RVR but HCV RNA<50IU/mL at wk12), partial EVR (non-RVR with a detectable but ≥2 log drop in HCV RNA at wk12) and non-EVR (<2log drop at wk12). SVR was defined as HCV RNA <50IU/mL after 24wks of untreated follow-up.

 

Results:

Data were available for 380 patients with advanced fibrosis/cirrhosis (G2 16wks=107; G2 24wks=99; G3 16wks=84; G3 24wks=90). Among patients treated for 16wks of therapy, SVR rates were 51% and 44% for G2 and G3 respectively and for 24wks of therapy SVR rates were 66% and 53% respectively. By MLR independent baseline factors predictive of SVR included lower body weight, higher alanine aminotransferase quotient, higher serum albumin level, higher platelet count, lower viral load, G2 infection and assignment to longer treatment duration. Among patients treated for 24wks, rates of RVR were substantially higher among G2 patients (Table). Rates of SVR among patients achieving an RVR and assigned to 24wks of treatment were 77% and 90% for G2 and G3 respectively and rates of SVR among patients achieving a complete EVR were 44% and 34% for G2 and G3 respectively. No patient with slower responses achieved an SVR.

 

Conclusions:

Among patients with advanced fibrosis/cirrhosis treated with pegIFN alfa-2a plus ribavirin, those infected with G2 HCV had higher rates of RVR and SVR compared to patients infected with G3 HCV. For patients achieving an RVR and treated for 24wks, rates of SVR were high for both G2 and G3 (77–90%). For both G2 and G3 patients with advanced fibrosis/cirrhosis abbreviated 16-wk therapy was less effective and should be strongly discouraged in this patient population.

 

Response at wk 4/12

G2
n=206

G3
n=174

RVR, n (%)
cEVR, n (%)
pEVR, n (%)
Non-RVR/EVR, n/N (%)

132 (64.1)
66 (32.0)
3 (1.5)
5 (2.4)

88 (50.6)
60 (34.5)
9 (5.2)
17 (9.8)

 


HCV treatment – General

 

1241. Interferon therapy for hepatitis C patients curatively treated for hepatocellular carcinoma with percutaneous therapies. 

T. Goto; H. Yoshida; R. Tateishi; K. Enooku; E. Goto; H. Yoshida; T. Sato; T. Ohki; R. Masuzaki; J. Imamura; N. Yamashiki; F. Kanai; K. Hamamura; S. Shiina; T. Kawabe; M. Omata

 

Aim:

Because of very frequent recurrence of hepatocellular carcinoma (HCC) after curative treatment in HCV positive (HBsAg negative) patients, the prognosis remains unsatisfactory. We investigated whether interferon (IFN)-based antiviral therapy was effective after complete treatment of HCC and improved survival.

 

Method:

From January 1992 through September 2006, a total of 1344 HCV-related HCC patients were completely treated with percutaneous therapies, i.e., percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy, and radiofrequency ablation. Among them, 112 patients (mean age 63.5 ± 6.3) received IFN-based therapy (HCC-IFN group). We compared the sustained virologic response (SVR) rate in HCC-IFN group with that in IFN-treated patients without HCC (n =392, mean age 55.2 ± 10.7). Survival was compared between patients in HCC-IFN group who achieved SVR and who did not. We also compared the survival between 70 patients with naïve HCC in HCC-IFN group and the same number of patients with HCC who did not receive IFN matched for sex, age, tumor size, tumor number, and Child-Pugh score.

 

Result:

The SVR rate in HCC-IFN group was 26% (19/72) and 57.5% (23/40) for serotype 1 and 2, respectively, which was compatible to that in non-HCC controls, 27.7% (73/264) and 68.6% (88/128), respectively. In HCC-IFN group, there was a trend of better survival in those who achieved SVR than in those who did not:

·        88% interferon treated group vs. 60% untreated group

 

Conclusion:

·        The SVR rate in HCC interferon group was comparable to that in non-HCC controls

·        Among 70 naive HCC patients with interferon treatment, 5 year survival rate was 88% in contrast to the survival rate of 60% in the matched control HCC patients without interferon treatment (p=0.0459)

 


HCV Treatment – General

 

1242. Sustained Virological Response in Patients with Chronic Hepatitis C is Similar Between Whites and Non-Whites: Evaluation Using Specific Ancestry Alleles Analysis in an Admixed Population. 

L. N. Cavalcante; K. Abe-Sandes; A. D. Angelo; D. C. Lemaire; L. S. Souza; E. S. Azevedo; J. d. Carvalho; T. M. Machado; P. S. Brandão; N. P. Santana; L. G. Lyra; A. C. Lyra

 

Several studies have suggested that ethnical background influences antiviral therapy response to chronic hepatitis C (CHC). African descendants appear to have a decreased sustained virological response (SVR) compared to whites.

 

Aims:

To evaluate the influence of ancestry determined by genetic polymorphisms analysis and by phenotype classification in antiviral therapy response of subjects with CHC.

 

Methods:

This is a case-control study. We evaluated HCV mono-infected patients who had been treated with combination of interferon and/or peg-interferon and ribavirin and divided them into two groups: A–patients who were non-responders/relapsers; and B–patients with SVR. The phenotype classification was performed using Krieger’s criteria (Krieger H, 1965). Genetic ancestry was determined by analyzing 7 loci autossomic People Specific Alleles (PSA) using PCR and Real-time PCR: APO, Sb19.3, FY-null, AT3-I/D, LPL, PV92, CKMM. We performed the Hardy-Weinberg test and compared allele’s frequencies and phenotype of patients to parental populations.

 

Results:

So far, 169 subjects who attended the outpatient clinic between February 2007 and April 2008 were consecutively included; 106 subjects were non-responders/relapsers; (78% were infected by HCV genotype 1; 3 of them were not classified according to phenotype), 63 had achieved SVR (71.4% had been infected by HCV genotype 1). Among group A, 47 patients (45.6%) were whites and 56 (54.4%) were non-whites; among group B, 30 patients (48.4%) were whites and 32 (51.6%) non-whites (OR=0.9; IC95%=0.45-1.77). So far we performed the ancestry allele’s analysis of the first 92 patients. Among the 42 non-responders/relapsers the rates of genetic ancestry contribution were: African, 41.1%; Indian, 9.3%; European, 49.6%; among the 50 SVR subjects, these rates were: African, 33.1%; Indian, 16.6%; European, 50.3%. These differences were not associated with a greater or lower chance of achivieng SVR or non-response. When analysis was performed with only HCV genotype 1 infected patients the results were similar. Ethnic phenotype classification using Krieger’s criteria and ancestry determined by molecular markers had strong correlation when compared to parental populations both among whites and non-whites (R square=0.99 and 0.98, respectively).

 

Conclusions:

Whites and non-white patients with CHC from an admixed population had similar SVR rates. We hypothesize that in this population the presence of a high frequency of PSAs of European markers in patients with African descent may balance the response rate between both ethnic groups. Thus, ethnic background can not be extrapolated as a predictor of therapy response to all populations.

 


HCV Treatment – Pegasys

 

1243. Effect of Time to Response on Viral Breakthrough and Relapse Rates in Patients Infected With HCV Genotype 1 and Treated With Peginterferon Alfa-2a Plus Ribavirin. 

M. L. Shiffman; F. M. Hamzeh; R. T. Chung

 

Aim

This retrospective analysis assessed the breakthrough and relapse rates based on the time to HCV-RNA negativity in patients with HCV genotype 1.

 

Methods

Patients from 4 clinical trials, 2 of which were enriched with difficult to treat patients, who were infected with HCV genotype 1 were treated for 48 wks with pegIFNα-2a 180 µg/wk and ribavirin 1000/1200 mg/d. Patients were grouped according to the time at which HCV-RNA negativity was first achieved: Wks 4 (RVR), 12 (cEVR), 24 (negative at Wks 13–24), 48 (negative at Wks 25–48), and 72 (SVR). Breakthrough and relapse rates were confirmed by positive HCV RNA and are presented as a percentage of total responders (TR) and total population (TP). Only patients with confirmatory data were included in the analysis. The impact of on-treatment exposure to ribavirin was assessed.

 

Results

Of 1243 patients analyzed, 67% were non-Latino whites, 23% were Latino whites, and 9% were African Americans. At baseline, 67% of patients were men, 71% were aged >40 yrs, 63% weighed >75 kg, 51% had a BMI >27 kg/m2, 15% had cirrhosis, 81% had a viral load >400,000 IU/mL, and 76% had an ALT quotient ≤3×ULN. Patients who responded early tended to be younger, weigh less, and have a lower BMI than patients with a later or no response. Patients who reached negativity before 24 wks had a similar end of treatment response (Table); however, patients who responded early (<12 wks) had lower breakthrough and relapse rates, which resulted in higher SVR rates, than those who responded later. On-treatment ribavirin analysis suggested that more patients achieved negativity when exposed to a higher average daily dose (66.4% for ≤13.7 mg/kg vs 77.6% for >13.7 mg/kg). In addition, patients (n=310) with a daily ribavirin dose of ≤11.93 mg/kg had higher breakthrough (12.2% vs 6.8%) and relapse (37.2% vs 28.5%) rates as a percentage of TR than those patients (n=932) with a dose >11.93 mg/kg.

 

Conclusion

Longer time to HCV-RNA negativity and lower ribavirin exposure tended to be associated with higher breakthrough and relapse rates which resulted in lower SVR rates. Patients who achieve viral negativity after Wk 12 may require a longer duration of therapy to prevent relapse. Maintaining optimal ribavirin dose may also avoid breakthrough and relapse.

 

 

Breakthrough %

 

Relapse %

 

 

Response group

N

TP

TR

EOT %*

TP

TR

Dropout %†

SVR %

RVR

195

5

6

81

2

2

18

75

cEVR

505

7

7

81

18

23

12

63

24-wk neg

194

12

13

84

45

58

10

33

48-wk neg

39

-

-

100

72

76

5

23

Total

933

7

8

82

22

29

13

58

*End of treatment response †While responding 

 


HCV Treatment – Predictors of Treatment Response

 

1249. Effect of obesity on interferon stimulated genes expression in chronic HCV infection. 

V. Aggarwal; C. S. Palmer; A. R. Lloyd; A. Zekry

 

Introduction:

Obese subjects with chronic HCV infection respond poorly to antiviral therapy with pegylated interferon and ribavirin. We utilized paired PBMCS prospectively collected at baseline and 12 weeks post commencing antiviral therapy, to compare interferon stimulated genes (ISGs) expression and signaling in obese and lean subjects with chronic HCV genotype 1 infection. We correlated the ISGs in each group with the response to treatment at 12 weeks of therapy (HCV PCR negative or drop in HCV viral load by>2log10)

 

Methods:

RT2- PCR (array superarray) was used to examine the expression of 96 ISGs. Western blot was used to examine protein extracts from PBMC using phospho-STAT-1 antibody.

 

Results:

PBMCS from 12 subjects; 6 obese (BMI>30kg/m2) and 6 lean HCV subjects were examined at baseline and 12 weeks after interferon based therapy (total of 24 samples). 6 subjects (3 obese and 2 lean) were non responders at 12 weeks. In all patients, 18% of ISG were increased by more than 2 folds at 12 weeks compared to baseline. These genes included ISG15, IFI6, IFI27, Viprin, USP18, MX1, MX2, OAS1 and OAS2. Compared to baseline however, the fold increase in each of these ISG genes at 12 weeks was significantly lower in obese than in lean subjects. Moreover, compared to lean subjects, obese subjects at 12 weeks had significantly enhanced expression of SOCS1, SOCS3, USP18 and IFI27 (p<0.05, paired t-test). As expected, the phosphorylation of pSTAT-1 at 12 weeks was reduced in all non-responders to therapy.

 

Conclusions:

Obese subjects with chronic HCV genotype 1 infection displayed increased expression of several ISGs in response to antiviral therapy. However, the magnitude of ISGs induction in obese subjects was significantly less robust to that observed in lean subjects. In parallel, the expression of negative regulators of interferon signaling including SOCS1, SOC3 and USP18 was significantly enhanced in obese subjects at 12 weeks of therapy compared to lean ones. This was associated with reduced activation of STAT-1 in response to interferon therapy. These result indicate that activation of negative feedback loops that inhibit interferon signaling plays an important role in compromising the success to interferon therapy in obese HCV subjects.

 


HCV Treatment – Pegasys

 

1251. Very Low Viral Load (VLVL) Relapse after Treatment for HCV: A unique group with High Sustained Virologic Response (SVR) to low dose, Short Course Retreatment. 

J. C. Hoefs; V. S. Aulakh

 

Introduction:

A sustained virological response (SVR) to treatment of naïve patients with chronic hepatitis C represents clinical cure and is 55% and some of these patients relapse (R) after being RNA negative during treatment. Most relapse  patients have RNA levels in blood after relapse that is similar to the RNA levels before any treatment at baseline (B). We report a unique group of five of 35 relapse patients (14 %) with sustained very low viral load (VLVL) for > 6-12 months post treatment off all medications.

 

Methods:

Five patients with VLVL relapse (RNA < 5000 IU/ml at 3 months post treatment) were compared to 30 relapse patients whose RNA levels returned to baseline post treatment. Serial blood tests, quantitative liver spleen scan (QLSS) and liver biopsies (LBx) were reviewed.

 

Results:

Five patients with VLVL relapse were all genotype 1 (compared to 12/21 of the other relapse  patients), had > 12 months of initial therapy, had a spike of high RNA level in blood within 3 months of end-of-treatment (EOT) and subsequently had a very low HCV RNA titer (<5000 IU/ml) at 3 months or a low titer that gradually increased with time remaining < 100,000 IU/ml. Compared to other relapse patients, the VLVL-R had a significantly (<.05) greater percent of cirrhosis (80% vs 23%), higher ALT (161+/-34 vs 76+/-59 U/ml) and lower baseline RNA (.38+/-.11 vs 8.66+/-11.98 million IU/ml). Rapid virologic response and early virologic response were similar in the two groups. Viral RNA levels in response to treatment and post-treatment follow-up are in the table. The patients were retreated with reduced amount and short course (6 months):

 

·        3 patients 180 ug week pegylated interferon/ plus 800 mg/day ribavirin

·        2 patients 90 ug weekly pegylated interferon alpha 2a plus 600-800 mg/day ribavirin

 

Conclusion:

Patients with VLVL relapse after HCV treatment:

·        Were unique:  cirrhosis, low baseline HCV RNA, genotype 1

·        Very responsive to low dose, short treatment with 100% SVR

·        Tolerant of retreatment despite high incidence of cirrhosis.

 


HCV Treatment – General

 

1252. Determinants of HCV Antiviral Treatment in a Managed Care Setting. 

M. Manos; V. Shvachko; W. Zhao; R. C. Murphy

 

Introduction:

Little is known about how hepatitis C patients are selected for antiviral treatment in community settings. Among HCV patients in a comprehensive managed care program, we identified the predictors of having received treatment.

 

Methods:

We studied adult HCV patients in the Northern California Kaiser Permanente Medical Care Program in December 2007 who had race/ethnicity data available (82%). Electronic records were extracted for years 1995-2007. For medical history we assessed the period prior to therapy in treated patients, and “ever” in the untreated.

 

Results:

Of 15,979 HCV patients included, mean age (in 2007) was 54 yr; 59% were male; 61% were white non-Hispanic, 16% Hispanic, 14% black and 9% Asian/PI; HIV co-infection 2.4%; chronic HBV 1.7%. Based on pharmacy records since 1995, a total of 3,494 (22%) were dispensed at least one HCV treatment (an interferon and/or ribavirin).

 

HCV genotype was available for 50% overall, and 88% of treated cases. Of patients ever treated, 32% had genotype 2 or 3, and 56% had type 1 or another type. Percent of HCV patients ever treated varied significantly among the 15 medical centers (12 - 31%). HIV status, or diagnoses of active alcohol/drug use, was not predictive of treatment.

 

The table shows, for significant factors, crude and adjusted (logistic regression) odds ratios for ever receiving treatment. When limited to patients with genotype, the model gave similar results; and the adjusted OR for genotypes 2/3 vs. 1/other was 1.77 (1.60 - 1.97). When Blacks and Hispanics were each assessed separately, residence in a high poverty area was no longer significant; and genotype remained predictive.

 

Conclusion:

In this comprehensively insured population, Blacks and Hispanics were less likely than other groups to have been treated, after adjustment for multiple confounding variables. This may reflect the anticipated lower response rates in these patients. Factors predictive of treatment included abnormal ALT, cirrhosis, viral genotype, female gender, no depression history, medical center, and age under 60.

 

Correlates of Being Treated for HCV

 

Crude OR

(95% CI)

Adj OR^

(95% CI)

Women

0.86

(0.80-0.93)

1.14

(1.05-1.24)

Age 60+

0.69

(0.63-0.76)

0.63

(0.57-0.69)

Asian/PI*

1.09

(0.96-1.24)

1.03

(0.90-1.19)

Black*

0.49

(0.43-0.55)

0.58

(0.50-0.67)

Hispanic*

0.95

(0.86-1.06)

0.82

(0.73-0.92)

Poor area**

0.60

(0.52-0.71)

0.78

(0.66-0.92)

ALT >2x ULN

3.26

(2.99-3.56)

3.23

(2.95-3.54)

Cirrhosis

2.05

(1.84-2.28)

1.62

(1.45-1.82)

Depression hx

0.65

(0.60-0.71)

0.62

(0.56-0.67)

^Adjusted for all factors listed, plus medical facility; *versus non-Hispanic white; **resides in high poverty area


HCV Treatment – General

 

1253. Assessment of serum HCV RNA at week 12 post-treatment is as relevant as week 24 to predict SVR in patients with chronic hepatitis C treated with Pegylated interferon plus ribavirin. 

M. Martinot-Peignoux; M. Ripault; S. Maylin; L. Leclere; N. Boyer; P. Marcellin

 

Introduction.

Sustained Virologic response (SVR), in patients with chronic hepatitis C treated with pegylated interferon alpha (PEG-IFN) + ribavirin (RBV) is defined by undetectable serum HCV RNA at the end of the 24 weeks post-treatment follow-up period. Once achieved SVR is durable.

 

Aim.

The aim of our study was to evaluate if 12 weeks post-treatment serum HCV RNA assessment could be as relevant as 24 weeks to identify patients with SVR.

 

Methods:

137 patients, consecutively treated with standard of care regimens of PEG-IFN alpha 2b + RBV, with an end of treatment response were included in the study. Serum HCV RNA was measured at 12 weeks and 24 weeks, after treatment cessation. A subset group of patients was analyzed 4 weeks after treatment cessation. SVR was defined as undetectable serum HCV RNA at the end of the 24 weeks post-treatment follow-up. Virologic relapse (VR) was defined as reappearance of detectable HCV RNA during the 24 weeks post-treatment follow-up. Serum HCV RNA was measured with the VERSANTR HCV RNA Qualitative Assay (TMA) (Siemmens). We evaluated the positive predictive value (PPV) of an undetectable serum HCV RNA to identify patients with SVR at week 4 and week 12 post-treatment follow-up.

 

Results.

At the end of the 24 weeks-post treatment follow-up 108/139 (78%) of the patients demonstrated a SVR and 31/139 (22%) patients demonstrated a VR. At week 12 post-treatment follow-up serum HCV RNA was undetectable in 108 patients, all were SVR: PPV for SVR was 100%;

 

Conclusions.

Our results show that the assessment of serum HCV RNA at week 12 post-treatment follow-up (PPV 100%) is as effective as week 24 to predict SVR. This result emphasizes that post-treatment follow-up to identify patients with SVR or VR could be shortened to 12 weeks.

 


HCV Treatment – Pegasys

 

1256. Higher Response Rate from Peginterferon Alpha 2a Plus Ribavirin in Chronic Hepatitis C Patients with Hemophilia. 

H. Sul; H. Kim; S. Chung; Y. Lee; S. Park; H. Lee; K. Yoo; S. Hwang; S. Chung; H. Oh; C. Choi; J. Kim; J. Do; J. Kim; S. Chang; S. Park

 

Background and Aims:

Chronic hepatitis C (CHC) is a major comorbidity in patient with hemophilia. However, eradication of hepatitis C virus in patient with hemophilia is little information on the efficacy and adverse events of antiviral therapy. In this open labeled and prospective study, the efficacy and tolerability of the combination therapy with peginterferon alpha-2a (PegIFN) plus ribavirin was evaluated in adult hemophiliacs with CHC.

 

Methods:

90 CHC Patients with hemophilia were enrolled between March, 2007 and March, 2008. Genotype 1 patients (G1, n = 55) received PegIFN (180 mcg, weekly) plus ribavirin (1000/1200 mg, daily) for 48 weeks while genotype 2 and 3 patients (G2/3, n = 35) received PegIFN (180 mcg, weekly) plus ribavirin (800 mg, daily) for 24 weeks. We evaluated rapid virologic response (RVR), early virologic response (EVR), and end-of-treatment response (ETR). Safety evaluations included adverse events and laboratory tests. This analysis was conducted by intent-to-treat.

 

Results:

Characteristics of the 90 patient included in this study are shown in the table 1. 6 patients (2%) were withdrawn from treatment. In 89 patients who treated more than 4 weeks, RVR was achieved in 51 patients (57%, G1=35%, G2/3=94%). In 86 patients who treated more than 12 weeks, EVR was achieved in 81 patients (94%, G1=93%, G2/3=97%). In 48 patients who completed the treatment schedule, ETR was achieved in 41 patients (85%, G1=81%, G2/3=94%). %). SVR was evaluable in 13 patients with genotype 2/3, and SVR was achieved in 11 patients (85%). There was no severe adverse event. Headache and hair loss were common. Hematologic adverse events were neutropenia (23%), anemia (16%) and thrombocytopenia (4%). Dose reduction of PegIFN was necessary in 10 patients (21%). On the other hand, it was 5 patients (10%) for ribavirin. Pretreatment viral load was a good predictive factor for RVR in multivariate analysis.

 

Conclusion:

PegIFN alpha-2a and ribavirin treatment showed higher response rate in CHC patients with hemophilia compared with non-hemophilic patients. There was no serious adverse event associated with bleeding except hepatic decompensation (n=1) and infection (n=1) during the treatment.

 


HCV Treatment – IDUs

 

1257. Adherence and response rate to anti viral treatment do not seem to be affected by intravenous drug use in patients with chronic hepatitis C under substitution therapy. 

S. Manolakopoulos; O. Anagnostou; M. Deutsch; E. Tiniakou; G. V. Papatheodoridis; E. K. Manesis; D. Tzourmakliotis; A. J. Archimandritis

 

Introduction:

Intravenous drug use (IVDU) is the main transmission route of hepatitis C virus. NIH expert panel states that IVDUs should not be excluded from treatment, however, active IVDUs are difficult to treat and are often denied treatment for hepatitis C due to concerns about adherence.

 

Aim:

The present study evaluates HCV treatment adherence and response rates among active and past IVDUs with or without methadone maintenance and the possible factors that may influence their outcome.

 

Patients and methods:

We have retrospectively studied 146 IVDUs (37% on methadone maintenance therapy, 12% with active substance use and 51% with a history of substance abuse who had disrupted > 1 year) with chronic HCV infection who had started treatment (interferon or Peginterferon α-2α or 2b with or without ribavirin) between 2000 and 2007. Data base included: gender, age, history of alcohol abuse (>50g/day), smoking habits, duration of drug use, histology when available, HCV genotype, baseline serum HCV RNA, data about patients follow up, treatment adherence, and treatment outcome. The end points of the analysis included treatment adherence and treatment outcome.

 

Results:

Among the 146 patients, 108 were males and 38 females with a mean age of 40.5 years SD + 8 (range 20-60). The mean duration of IVDU was 9+7.3 years, 65% of the patients reported >50g/day alcohol consumption and 93% were smokers. The mean baseline HCV RNA was 1.9x106, 36,4% had genotype 1-4 and 11,5% advanced fibrosis.

 

Overall, 110 patients (75, 4%) were adherent to anti-HCV therapy. Adherence was independent of treatment duration and was not significantly different between the patients with active use, methadone substitution or past use. 36/146 patients (24,6%) discontinued treatment prematurely, after a mean of 3±2 months (17% due to side effects and 14% by their own decision)

 

Among the 81 patients who fulfilled treatment schedule overall SVR rates were 58,6% not significantly different between the three study groups (61,8% in methadone treated, 58,8% active users, 50% among past users) or between genotypes (48,4% genotype1-4, 63,2% genotype 2-3). Adherent patients were significantly more likely to achieve SVR compared with non-adherent patients (58,6% vs 19,5% P<0.01). Adherence to treatment, younger age and male gender were the only factors associated significantly with SVR on multiple regression analysis.

 

Conclusion:

·        Our data clearly show that in active or past IVDUs with chronic hepatitis C adherence is significantly associated with SVR.

·        SVR did not differ among active user’s and those on maintenance therapy who remain adherent to HCV therapy.

·        Therefore our results reinforces recent recommendations and support that IVDUs with HCV infection should not be excluded from antiviral treatment.

 


HCV Treatment – Predictors of Treatment Response

 

1259. Steatosis, Insulin resistance, Iron overload, Fibrosis and Viral load as negative factors affecting Early (EVR) and Sustained (SVR) Virological Response in patients with Chronic Hepatitis C treated with peginterferon and ribavirin. 

E. F. Georgescu; R. Ionescu; G. Florescu; G. Mateescu; L. Vancica

 

Introduction:

Since the relation between hepatitis C virus infection, insulin resistance and iron overload is not fully understood in genotype 1 HCV-infected patients, our aim was to evaluate the impact of several biochemical (serum ferritin, uric acid, HOMA-IR), histological (fibrosis, necroinflammation, steatosis, and hepatic iron scores) and viral factors (HCV viraemia) on both EVR and SVR in patients with genotype 1 chronic hepatitis C (CHC) treated with peginterferon plus ribavirin.

 

Patients and Methods:

We evaluated retrospectively 188 naïve CHC patients receiving peginterferon plus ribavirin at standard weight-based doses for 48 weeks (96M/92F; mean age 42.75 ± 0.84; mean weight 69.63±1.11 Kg; mean BMI 24.03±0.4). Genotype 1 HCV was confirmed in all cases by PCR analysis with type-specific primers for identification. Biopsies were assessed for inflammatory activity and fibrosis, as quantified by the modified Knodell histological activity index. Steatosis was categorized by the proportion of hepatocytes per low-power field with fatty changes: >5%, >5–33%, 34–66%, >66%. Biopsies were also assessed for stainable iron using the Brissot scoring system. All subjects were evaluated for metabolic syndrome (MS) using the NCEP-ATPIII criteria while HOMA-IR was estimated before treatment using the formula [fasting glucose (mg/dL) × immunoreactive insulin (µU/mL)]/405. All parameters were introduced in multivariate analysis in order to evaluate their contribution to EVR and SVR.

 

Results:

EVR was achieved in 115/188 pts (61.17%) while SVR occurred in 82/115 (71.3%). After adjusting for sex and age, independent factors that negatively interfered with both EVR and SVR were: fibrosis score (OR: 0.478; 95%CI: 0.140-0.912; P=0.031), steatosis (OR: 0.138; 95%CI: 0.035-0.537; P=0.004), iron score (OR: 0.308; 95%CI: 0.143-0.665; P=0.003), HOMA-IR index (OR: 0.478; 95%CI: 0.266-0.857; P=0.013) and viral load (OR: 0.424; 95%CI: 0.240-0.746; P=0.003). After excluding the patients with MS criteria (n=32), EVR was observed in 102/156 (65.4%) and SVR in 82/102 (80.4%). Factors that independently influenced both EVR and SVR were: fibrosis score (OR: 0.468; 95%CI: 0.295-0.743; P=0.001), steatosis (OR: 0.535; 95%CI: 0.342-0.834; P=0.006), iron score (OR: 0.779; 95%CI: 0.650-0.935; P=0.007) and viral load (OR: 0.784; 95%CI: 0.650-0.945; P=0.011).

 

Conclusion:

Fibrosis, steatosis and iron scores, as well as viral load are independent parameters that can affect both EVR and SVR in genotype 1 CHC patients treated with peginterferon and ribavirin at standard doses for 48 weeks, regardless the presence of MS. If MS is present, high HOMA-IR index can also additionally impair viral response.

 


HCV Treatment – Predictors of Treatment Response

 

1260. Monitoring virologic on treatment response to predict treatment outcome in patients with chronic hepatitis C treated with pegylated interferon plus ribavirin: realtime PCR assays and bDNA/TMA provide the same performances. 

M. Martinot-Peignoux; S. Maylin; H. Khiri; L. Leclere; M. Ripault; P. Marcellin; P. Halfon

 

Introduction:

It well established that measurements of baseline HCV RNA and early virologic response are the key parameters for tailoring treatment outcome in patients with chronic hepatitis C. Different assays have been developed for the quantification of HCV RNA in routine clinical practice.

 

Aim:

Our aim was to compare the clinical performance of 3 commercially available assays to evaluate the positive predictive value (PPV) and the negative predictive value (NPV) of baseline viral load (BVL), rapid virologic response at week 4 (RVR) and early virologic response at week 12 (EVR).

 

Methods:

283 patients consecutively treated with standard of care regimens of pegylated interferon alpha 2b + ribavirin were studied (155 naïves; 128 non-naives). Serum HCV RNA was measured at baseline, week 4, week 12, end of treatment and 6 months after the end of treatment SVR was defined as undetectable serum HCV RNA at the end of 6-month post-treatment follow-up. HCV RNA measurements were performed with the VERSANTR HCV 3.0 Assay (bDNA) (Siemens), samples below the limit of quantification were tested with the VERSANTR HCV RNA Qualitative Assay (TMA) (Siemmens) (bDNA/TMA); the Cobas Ampliprep/Cobas TaqMan (CAP/CTM) (Roche Molecular Systems); and the Abbott m2000sp extraction/m2000rt amplification system (ART) (Abbott Laboratories).

 

Low BVL was < 400 000 IU/ml (PPV), RVR was defined as undetectable serum HCV RNA or ≥2 log drop decline of BVL at week 4 (PPV) and non-EVR was defined as detectable serum HCV RNA or log drop < 2 log decline of BLV at week 12 (NPV) of therapy.

 

Results.

Overall SVR rate was 48%. The median BLV were: 5.56 (2.60-6.82), 5.19 (2.80-7.48) and 4.63 (2.23-6.58), with bDNA/TMA, CAP/CTM and ART, respectively (p<0.001. Median viral load were G1: 5.66 and 5.51 vs 4.59 (p<.001); G2: 5.79 and 5.86 vs 5.35 (p<.001); G3: 5.68 vs 5.00 vs 4.40 (p<0001); G4: 5.52 vs 4.50 and 4.56 (p<.004), with bDNA/TMA, CAP/CTM and ART, respectively.

 

Conclusions.

1.     Monitoring of therapy should include both, detection of serum HCV RNA at week 4 to predict SVR and at week 12 to predict non-SVR.

2.     Both 3 assays show the same performance to evaluate RVR or non-EVR. However, assays show viral load discrepancy according to HCV genotype, it is therefore important to consistently use the same HCV RNA assay throughout treatment patient follow-up.

 

 

 

PPV

PPV

PPV

NPV

NPV

 

Baseline

Week 4

week 4

Week 12

Week 12

Viral Load

<5.602 log UI/ml

Undetectable

≥ 2log drop

Detectable

<2log drop

bDNA/TMA

59%

97%

68%

85%

93%

CAP/CTM

57%

91%

70%

92%

84%

ART

55%

94%

70%

81%

74%

 


HCV Treatment – General

 

1261. The Impact Of A Multi-Disciplinary Support Program On Adherence And The Efficacy Of Hepatitis C Treatment. 

M. Garcia-Retortillo; I. Cirera; M. Giménez; C. Marquez; J. Galeras; P. Castellví; R. Navinés; E. Clot; E. Salas; F. Bory; R. Martín-Santos; R. Solà

 

Introduction:

Adherence to antiviral treatment has been cited as a potentially important factor in determining the outcome of therapy in hepatitis C patients.

 

Aim:

To evaluate the impact of a multi-disciplinary support program (MSP) on the fulfilment and efficacy of hepatitis C treatment.

 

Methods:

We included 278 hepatitis C naive patients treated consecutively from June 2001 to June 2006. All patients were treated with Peg-IFN alfa-2a 180 µg/week and ribavirin (RBV) (G1/4:1000-1200, 12 months G2/3: 800, 6 months). Patients were divided into two groups: Group 1: 131 patients, included in MSP, and Group 2: 147 patients who were conventionally controlled. The MSP team includes hepatologists, nurses, a pharmacist, a psychologist and a psychiatrist. Uniform patient education, open and flexible visits scheduling, continuing evaluation of psychiatric risk (PHQ and HADS), active medication control and standardized management of the secondary effects were carried out during MSP. Patients receiving ≥80% of each assigned drug for ≥80% of the expected therapy duration were considered adherent to the treatment.

 

Results:

No differences were observed between groups in terms of age, gender, HCV-genotype, viral load and fibrosis degree. Anti-depressives or anxiolytics were prescribed in 45 (34.3%) and 34 (23.1%) patients in each group, respectively (P 0.04). Haemoglobin levels decreased during treatment in 17.6 and 22.4% in both groups (P: NS) even though erythropoietin was used only in 5.3 and 4.1%, respectively.

 

Conclusions:

The multi-disciplinary attention program improved the adherence to treatment and increased its effectiveness, particularly among genotype 1 patients.

 

Group 1

Group 2

Adherence (%)

94.6

78.9

Withdrawal/drop-out (%)

4.4

6.2

Drug dosages <80% (%)

0

13.4

Peg-IFN dosage 100% (%)

94.6

76.2

RBV dosage 100% (%)

90.8

68.7

Sustained virological response (%)

77.1

61.9

Genotype 1

66.7

48.1

Genotype 2/3

87.7

81.4

 


HCV Treatment – Side Effects

 

1263. Prospective Analysis of Depression During Antiviral Treatment for Hepatitis C: Results of the VIRAHEP-C Study. 

D. M. Evon; D. Ramcharran; S. H. Belle; N. Terrault; R. J. Fontana; M. W. Fried

 

Background:

Peginterferon and ribavirin therapy for chronic hepatitis C is commonly associated with depressive symptoms, which may affect quality of life and the outcome of treatment.

 

Aims:

To assess the frequency and factors associated with depression occurring before and arising during treatment, and examine the relationship between depression and sustained virological response (SVR) rates.

 

Methods:

Prospectively collected data from the VIRAHEP-C study were analyzed. 196 African Americans and 205 Caucasian Americans with chronic hepatitis C were treated with peginterferon and ribavirin for up to 48 weeks. In this analysis, depression was defined as a score of >23 on the Center for Epidemiologic Studies Depression (CES-D) scale, collected before treatment and at weeks 4,12,and 24. Study personnel were blinded to CES-D scores, which were not part of the overall depression detection and management guidelines for the study. Other markers of depression analyzed included antidepressant use, psychiatric adverse events, a single item of depression on a visual analog scale, and two depression detection questions which assessed “feeling depressed, sad, or blue” and “feeling helpless about the future”. Results: Before treatment, 47 (12%) participants endorsed CES-D scores >23, which was associated with 10 factors, including younger age, female sex, poor social support, use of antidepressants, and endorsement of other markers of depression. Compared to those with CES-D scores <23, these 47 participants had higher rates of treatment discontinuation (13% vs 38%, respectively, p<0.0001), psychiatric adverse events (17% vs 30%, p=0.04), and new antidepressant medication use after starting antiviral therapy (27% vs 58%, p=0.0003); however, there were no differences in SVR rates (40% vs 38%, respectively, p=.079). The cumulative incidence of new onset depression was 13%, 21% and 26%, at 4, 12, and 24 weeks of therapy. SVR rates were not statistically different among patients who developed new depression and those who did not (47% vs 38%, p=0.16). Multivariable analyses indicated that new onset depression was associated with younger age, poorer social support, and symptoms of feeling “sad or blue.”

 

Conclusions:

Participants with pre-existing depression, as measured by CES-D, were at greater risk for psychiatric adverse events, need for antidepressants, and treatment discontinuation, although SVR did not suffer. New onset depression developed in ~25% of participants and did not differ by race, nor affect SVR rates. Poor social support, younger age, and symptoms of feeling sad or blue at baseline are risk factors for new-onset depression during antiviral treatment.

 


HIV/HCV Coinfection

 

1265. Treatment Rates of Hepatitis C Virus (HCV) Infection Among Patients Co-Infected With HIV Over The Past Decade In An Urban Medical Center. 

P. Suwandhi; K. Gopal; P. Benias; C. Wong; D. Meyer; H. C. Bodenheimer; A. D. Min

 

Introduction:

HIV related mortality in HCV/HIV co-infected patients had decreased with advent of antiretroviral therapy (ART), but liver related mortality has risen significantly. Therefore, guidelines recommend HCV treatment evaluation in all HCV/HIV co-infected patients.

 

Aim:

The aim of this study was to investigate HCV treatment rates in HCV/ HIV co-infected patients and treatment barriers at our center.

 

Methods:

We reviewed charts of all HCV/HIV co-infected patients referred for HCV treatment from 1998-2007.

 

Results:

There were 326 HCV/HIV co-infected patients with majority male (227;70%). 196 (60%) had HCV genotype 1. Mean CD4 count was 458 cells/mm3 (range 4-1532). HIV viral load was undetectable in 157(48%) patients with 266(82%) patients on ART. History of IVDU and active alcohol intake was documented in 217(67%) and 59(18%) patients, respectively. Sixty-three (19%) had history of depression and other psychiatric co-morbidities. After referral, 41(13%) patients did not show up for any appointment and 23(7%) patients (positive anti-HCV) had undetectable viral load by PCR. Liver biopsy was performed on 171(65%) of the 262(80%) patients evaluated for treatment, and advanced fibrosis (stage 2–4) was noted in 103(60%) patients. Eighty-four (32%) of 262 patients were treated, including 66 patients with liver biopsy. Number of liver biopsies and patients treated over the 10-year period is shown in the figure. Common reasons for not starting treatment were 59 (23%) patients lost to follow up, 40 (15%) with significant (medical/ psychiatric) co-morbidities, 25 (10%) with minimal liver disease on biopsy and 18 (7%) with patient’s refusal. Fifty (19%)  patients completed treatment. Treatment was withdrawn in 34 (13%) for the following reasons: patient lost to follow up (11; 4%), treatment complications (16; 6%), active IVDU (2; 0.7%), unknown causes (5; 2%).

 

Conclusions:

·        Number of co-infected patients referred for HCV treatment has plateaued over the past several years.

·        Only a minority of HCV/HIV co-infected patients were deemed eligible for and received HCV treatment over the past decade.

Thirty percent of the patients were deemed ineligible for treatment and 10% discontinued treatment due to patient control factors. Development of patient focused educational program may impact these factors and increase treatment rates and compliance.

 

 


HCV Treatment – General

 

1266. Education Program (Ep) Improves The Rate Of Sustained Virologic Response (Svr) To Anti-HCV Therapy: Multivariate Analysis From A French Network Experience. 

E. Collin; S. Fratté; A. Baudu; M. Thévenot; T. Thévenot; E. Monnet; V. Di Martino

 

Introduction:

Poor tolerance to anti-HCV therapies may lead to decreased compliance, more frequent dose reductions of and/or treatment discontinuations, then reducing the SVR rates.

 

Since 2003, a education program (EP) dedicated to patients undergoing anti-HCV therapy was implemented in two centers, involving three trained nurses. An educational program  has been systematically proposed to the patients on starting treatment.

 

Aim:

The aim of this study was to evaluate the impact of an educational program  on SVR and outcome of anti-HCV therapy through multivariate analyses.

 

Methods:

From March 2003 to October 2006, we collected data from all patients undergoing antiviral therapy for chronic hepatitis C. The impact of an educational program  on SVR was assessed through multivariate analysis adjusted on well-known factors associated with SVR (i.e., genotype, HIV co-infection, high HCVRNA load, severe fibrosis (F3F4)), age and center. Occurrence and types of adverse events were notified. Primary outcome was the frequency of SVR, secondary outcomes were dose adjustment and/or dose cessation of pegylated interferon or ribavirin.

 

Results:

258 patients (149 males; 48yrs) were included. 19 (7.4%) were HIV positive, 128 (58.4%) had high viral load, 84 (32.6%) were infected by HCV-genotype 2 or 3, 66 (29.7%) had F3/F4 fibrosis. As compared with patients not receiving an educational program , the 97 patients (37.6%) who received an educational program  were similars regarding genotype, histology, or HIV status. SVR was achieved for 120 patients (46.5%), more frequently in patients receiving an educational program  (56.7% vs. 40.4%, p=0.01). Doses reductions of PEG-Interferon or ribavirin were prescribed equally for patients with or without an educational program  (32.9% vs.24.2%, NS); similarly, premature treatment discontinuations, always following medical decision, occurred equally in patients with or without an educational program  (28.9% vs. 27.3%, NS). In multivariate analysis, factors associated with SVR were: HCV-type 2 or 3 (OR=5.5, p<0.0001), absence of HIV co-infection, OR=4.5, p=0.013), fibrosis.

 

Conclusion:

1.     After adjustment on well-known non response factors, an educational program substancially improves SVR for patients ongoing anti-HCV therapy.

2.      This result was not explained by a decrease in prescribed treatment discontinuation or doses reductions. It may be the consequence of a better adherence to anti-HCV therapies, suggesting that standard medical follow-up is associated with more frequent lack of compliance.

 


Liver Transplantation – HCV Treatment

 

1268. Prospective randomized study of antiviral therapy post-transplantation: effect of the type of pegylated IFN and baseline immunosuppression. 

C. Ortiz; F. Lopez-Labrador; R. Canada; B. Risalde; V. Aguilera; M. Prieto; M. Berenguer

 

Introduction:

Antiviral therapy post-liver transplantation (LT) has a limited efficacy. There is an interest in determining factors associated with sustained virologic response (SVR).

 

Aim:

To assess whether the kinetics of viral response in LT recipients treated with pegIFN-ribavirin differ depending on the baseline immunosuppression (tacrolimus-Tac- vs cyclosporine-CsA-) and type of IFN (pegintron vs pegasys).

 

Methods:

Ongoing prospective randomized study of LT patients randomized to pegintron vs pegasys in combination with ribavirin started in 2006. A detailed kinetic study was performed in 16 LT patients (Tac-pegasys, n=4, Tac-pegintron, n=4; CsA-pegasys, n=4; CsA-pegintron, n=4) and 4 immunecompetent patients (2 Pegintron and 2 Pegasys).

 

Results:

Of 65 patients randomized during 2006-2007, complete follow-up (6 months post-treatment) is available in 25 patients (pegasys, n=13; pegintron, n=12). There were 21 men, with a median age of 58 years (range: 39-69). Baseline immunosuppression consisted of Tac in 17, cyclosporine in 8. The overall SVR was 24%, not statistically different between the two groups (pegasys 31% vs pegintron 17%, p=.6). The SVR did not differ based on baseline immunosuppression (tacrolimus: 29% vs cyclosporine: 13%; p=.6). The only variables associated with SVR included baseline viremia (p=.05) and rapid virologic response (p=.006). No differences in viral decline at 1 day, 1 week, 1 month and 3 months were observed between the four groups. A trend towards a more pronounced viral decline at the 3 time-points was observed in the 4 immunecompetent patients compared to the 16 LT recipients.

 

Conclusions:

In recurrent hepatitis C, there are no differences in early viral kinetics between pegIFN alfa-2a and 2b regardless of baseline immunosuppression (Tac vs CsA).

 


HIV/HCV Coinfection

 

1269. Antiretrovirals reduce Ribavirin exposure in HIV-HCV coinfected patients. 

J. Quioc; V. Jullien; V. Mallet; B. Nalpas; S. Pol

 

Introduction and Aim:

Response rates under treatment with Peg-interferon and ribavirin are lower in HIV-HCV-co-infected than in HCV-mono-infected patients. A lower exposition to RBV could explain this difference. The end-point of our study was to compare serum ribavirin (RBV) levels in treated mono- and co-infected patients receiving the same dose of RBV.

 

Patients and Methods:

Serum RBV level was measured in 98 patients receiving Peg-interferon and RBV. There were 64 mono-infected patients and 34 co-infected patients. Per-therapeutic RBV levels were measured by high-performance liquid chromatography.

 

Results:

Among baseline characteristics, medians of age (41 vs. 48 years, P=0.001) and of body mass index (22.6 vs. 24.7, P=0.04) were lower in co-infected patients. Median CD4 count was 430/mm3 in HIV-infected patients and five of them did not receive any antiretrovirals (ARV).

 

There was no difference in RBV intake between mono- and co-infected patients (13.3 vs. 12.9 mg/kg; P=0.240). The rates of end of treatment (EOT) and of sustained viral (SVR) responses in HIV-positive and HIV-negative patients were 52.9% vs. 64.1% (P=0.386) and 35.3 vs. 50% (p=0.203) respectively.

 

There was no association between serum RBV concentrations and response rates (EOT or SVR) in HIV-positive and HIV-negative patients. In the subgroup of patients infected with a genotype 1-4, the median RBV level was higher in patients who achieved an EOT response (4.2 vs. 2.9 μg/ml, p=0.08), but was not associated with SVR. RBV concentration was not influenced by fibrosis stage (METAVIR F0-2 vs. F3-4).

 

Median RBV concentration was significantly lower in co-infected (2.5 μg/ml; IQR 1.3 to 3.8) than in mono-infected patients (3.2 μg/ml; IQR 2.5 to 5.1) (p=0.005). Among co-infected patients, the median RBV concentration was significantly lower (2.2 μg/ml; IQR 1.2 to 2.9) in patients treated by ARV than in patients without ARV (4.0 μg/ml; IQR 3 to 9.1) (p=0.02). There was no difference in RBV concentration between mono-infected and co-infected patients without ARV (P=0.302).

 

Conclusion:

Despite a comparable intake of RBV, serum concentration of RBV was lower in co-infected patients under ARV than in mono-infected patients. This could be explained by a metabolic interaction between ARV and RBV. Although we did not observe any association between RBV concentration and response rate in this retrospective study, this effect could participate to the lower response rates observed in other studies in co-infected patients.

 


HCV Treatment – Predictors of Treatment Response

 

1270. Insulin-Resistance in Chronic Hepatitis C patients: New Predictor of Sustained Virological Response Independent of HCV Genotype and Liver Fibrosis Stage. 

R. Moucari; M. Ripault; M. Martinot-Peignoux; H. Voitot; S. Maylin; A. Cardoso; T. Asselah; N. Boyer; M. Vidaud; D. Valla; P. Bedossa; P. Marcellin

 

Background & Aim:

Insulin-Resistance (IR) has been previously shown to impair sustained virological response (SVR) rate in chronic hepatitis (CHC) patients infected with genotype 1 when treated with pegylated interferon and ribavirin.

The aim of this study was to assess the independent impact of IR after adjustment to major predictors of SVR, particularly HCV genotype and liver fibrosis stage.

            

Patients and Methods:

167 consecutive non-diabetic treatment-naïve CHC patients, treated in our centre with pegylated interferon plus ribavirin, were prospectively assessed. Insulin resistance was assessed using the Homeostasis Model (HOMA-IR). HCV genotype was determined by sequencing. Serum HCV RNA was quantified using bDNA (Bayer Versant HCV RNA 3.0 Assay). Liver histology was assessed using the METAVIR score. SVR was defined as undetectable serum HCV RNA 24 months after treatment stopping.

 

Results:

Baseline characteristics were: male gender (66%), mean age (46±9 years), mean BMI (24±4 kg/m2), excessive alcohol consumption (9%). Blood transfusion and intravenous drug injection were the principal source of transmission (52%). HCV genotype distribution was: 1 (47%), 2 (7%), 3 (24%), and 4 (22%). Mean serum HCV RNA level was 5.5±0.7 log10 IU/mL, and 42% of patients had high serum HCV RNA level (>600 000 IU/mL). Median value of HOMA-IR was 2.1 (IQL range 1.1-4.6). Liver histology showed moderate-severe necroinflammation (METAVIR score A2-A3) in 46%, severe fibrosis (METAVIR score F3-F4) in 32%, and severe steatosis (>30%) in 29% of patients.

 

By univariate analysis, SVR was associated with HOMA-IR, HCV genotype, serum HCV RNA level, liver fibrosis stage and steatosis. Patients with HOMA-IR <2 achieved higher SVR rate than those with HOMA-IR >2 (72% vs. 44% respectively, p<0.01). Patients infected with genotypes 2 and 3 achieved higher SVR rates than those infected with genotypes 1 and 4 (79% vs. 46% respectively, p<0.001). Patients with low viral load achieved higher SVR rate than those with high viral load (67% vs. 44% respectively, p<0.01). Patients with mild-moderate fibrosis achieved higher SVR rate than those with severe fibrosis (62% vs. 44% respectively, p<0.05). Patients with mild-moderate steatosis achieved higher SVR rate than those with severe steatosis (62% vs. 42% respectively, p<0.05).

 

By logistic regression, SVR was associated only with HCV genotype 2 and 3 (p<0.001, OR=4.5, CI=2.0-9.8) and with HOMA-IR <2 (p<0.01, OR=2.8, CI=1.4-5.5)

 

Conclusion:

1.     Insulin-Resistance is a major negative predictor of SVR in CHC patients treated with pegylated interferon plus ribavirin.

2.     Impact of IR is independent of HCV genotype and liver fibrosis stage.

 


HCV Treatment – General

 

1271. Insulin Resistant Chronic Hepatitis C (CHC): The Effect of Sustained Virological Response (SVR) on Insulin Resistance (IR) Status, Insulin Secretion, Lipid Profile and Adiponectin. 

W. Soliman; M. Kuczynski; N. Perez-Gutierrez; I. Fantus; E. Heathcote

 

Introduction & Aim:

CHC may be associated with insulin resistance (IR). IR whether hepatic, peripheral or both i.e., low total body insulin sensitivity (ISI) may predate development of diabetes. IR is associated with changes in lipid and adipokine profiles. The study aim was to assess the prevalence and predictors of IR in treatment naïve, non-cirrhotic, non-diabetic patients with CHC and to assess the effect of achieving SVR on IR, insulin secretion, lipid profile and adiponectin in patients found IR pre-treatment.

 

Methods:

Hepatic IR was determined using the homeostatic model assessment (HOMA). Those with a HOMA ≥ 2.1 i.e., hepatic IR pretreatment were initiated on peg IFNα 2a 180 mcg/wk plus ribavirin (weight based). Serum glucose and insulin, HOMA, ISI and disposition index (measure of pancreatic insulin secretion) were assessed at baseline, 12 weeks into therapy and 6 months post-therapy by performing the oral glucose tolerance test. Serum adiponectin and lipid profile were measured at baseline and 6 months post-therapy.

 

Results:

In patients with non-cirrhotic CHC (108), hepatic IR was detected in 39%; its presence was independently associated with BMI [p= 0.0175, overweight odds ratio (OR) = 4.89 & obesity OR = 9.59] and histological activity index [p=0.0096, activity grade ≥ 2 OR = 3.81].Of the 17 patients who have completed antiviral therapy and follow up, 4 were null responders and 13 with hepatic IR and mean ISI of 10.3±7.7 (NR> 5) achieved SVR and IR improvement [HOMA post treatment (1.84±0.63) vs. pretreatment (3.28 ±0.94) , p<0.0008]. Ten of them lost hepatic IR (HOMA < 2.1) 6 months post treatment. Changes (post vs. pretreatment) in BMI, insulin secretion and AUC for glucose and insulin were insignificant. An increase in mean post treatment ISI (12 ±3.9) was noted but was not significant. A decrease of IR usually leads to reduction in total triglycerides (TG) but in our patients the levels of cholesterol, TG and HDL (post vs. pretreatment) increased significantly [p value = 0.0056, 0.0318 & 0.0264 respectively]. Levels (post vs. pretreatment) of LDL, free fatty acids (measured in 10 patients) and adiponectin (measured in 9 patients) were not significantly different.

 

Conclusion:

SVR may reduce or even eliminate prior hepatic IR in non-cirrhotic CHC; however SVR has no significant effect on ISI, insulin secretion or adiponectin levels. SVR was associated with an increase in levels of serum cholesterol, TG and HDL.  These results suggest that HCV or HCV-induced inflammation may be involved in the pathogenesis of the hepatic IR independent of adiponectin; they also indicate that in CHC patients with hepatic IR, the virus might affect lipid metabolism independent of hepatic IR.

 


HCV Treatment – Predictors of Treatment Response

 

1273. Asian Ethnicity is a Significant Predictor of Sustained Virologic Response (SVR) to Combination Therapy with Peginterferon (PEG IFN) and Ribavirin (RBV) in Chronic Hepatitis C (CHC). 

P. Vutien; N. H. Nguyen; R. T. Garcia; H. N. Trinh; L. H. Nguyen; E. B. Keeffe; G. Garcia; K. K. Nguyen; H. A. Nguyen; B. S. Levitt; M. H. Nguyen

 

Introduction:

Chronic hepatitis C (CHC) affects an estimated 169 million persons worldwide, of which 95 million are from East Asia. The vast majority of studies of HCV have been conducted in Western countries. A few small studies to date have suggested that Asian patients with CHC may have higher SVR rates than non-Asian patients. Our goal is to compare treatment response to PEG-IFN + RBV in a large cohort of Asian Americans (AA) and Non-Asians (NA) with HCV genotypes 1 and 2/3.

 

Methods:  

We performed a cohort study of 219 consecutive patients (AA=136, NA=83) with treatment-naïve CHC who were treated with standard dose PEG-IFN + RBV from 1/2001 – 11/2007 at two community-based GI clinics in the U.S. HCV RNA > 800,000 IU/mL was categorized as high viral load (HVL). Treatment adherence was defined as receiving ≥80% of PEG IFN and RBV dose and for ≥80% of intended duration. Analysis was by intention-to-treat. Multivariate analysis was performed to identify potential predictors of SVR.

 

Results:  

There were no statistically significant differences in age, sex, and baseline ALT levels between AA and NA. There was a trend for higher proportion of HVL in AA compared to NA: 65 % vs. 53% (p=0.12). There was no statistically significant difference in treatment withdrawal rate between AA and NA; however, overall adherence rate was lower in AA: 52% vs. 37% (p=0.032). AA were more likely to receive a RBV reduction than NA: 32% vs. 19% (p=0.08), while NA were more likely to receive PEG IFN reduction: 10% vs. 4% (p=0.066). 32% of AA received erythropoietin (EPO) compared to 16% of NA (p=0.009). There were no significant differences in SVR rates between AA and NA with genotypes 2/3 (82% vs. 79%, p=0.76). SVR for AA with genotype 1 appeared higher than SVR in NA, but this did not reach statistical significance: 58% vs. 46%, p=0.17). However, following adjustments for age, genotype, treatment adherence, and viral load, Asian ethnicity was a significant independent predictor of SVR (Table).

 

Conclusions:  

Asian ethnicity is a significant predictor of SVR; however, AA have a lower treatment adherence rate and this may be due to lower tolerability to RBV. Aggressive supportive care including preemptive use of EPO may be considered to maximize SVR in AA.

 

 


Diagnostic Tools – Biopsy – General

 

1274. Current Opinion Regarding the Utilization of Liver Biopsies in the Management of Hepatitis C: A National Survey. 

D. J. Weinerman; R. Chadalavada; K. D. Mullen

 

Aim:

Hepatitis C is the most common cause of cirrhosis and is the foremost reason for liver transplantation in the United States. Although liver biopsy (LB) is commonly performed prior to initiating treatment of hepatitis C (HCV), there are no guidelines that clearly state which patients should have a LB. The American Association for the Study of Liver Diseases (AASLD) position paper from 2004 supports but does not mandate LB for the purpose of influencing when to initiate treatment or for determining prognosis. The aim of this study is to explore the utilization of LB in the management of patients with HCV.

 

Methods:

An online survey was created and emailed to 2,203 members of a national liver association, of whom 85% are physicians (N=1,865).

 

Results:

A total of 421 completed surveys were received, 89% from physicians (N=375): 73% academic or university affiliated and 27% private practitioners. The most common situations for performing a biopsy always or most often were concern for other causes of liver disease (90%), genotype 1 (85%), concern for advanced liver disease (67%), African American race (66%), history of significant alcohol abuse (65%), a high viral load (over 850,000) (58%), and a normal ALT and AST (52%). The most common reasons given for never or only rarely performing a biopsy were imaging meeting criteria for cirrhosis (58%), platelet count of 60,000 (52%), genotype 2 (37%), genotype 3 (31%) and patient age under 25 (29%). In scenarios where a patient refused treatment and in cases where a patient requested treatment regardless of the biopsy result, there was a Gaussian distribution with wide variability. Most practitioners would either rarely biopsy (50%) or never biopsy (37%) after successful treatment of HCV.

 

Conclusion:

There is currently a variety of opinions regarding the role of LB in patients with HCV. This study supports LB in patients with genotype 1 or when there is concern for other causes of liver disease. When the imaging meets criteria for cirrhosis or after successful treatment of HCV, LB may be rarely indicated. It is possible that recent advances in HCV treatment and new modalities for assessing fibrosis may affect decisions pertaining to liver biopsies. This study shows the current range of perspectives among practicing hepatologists across the nation and may be helpful in the formulation of future guidelines.

 

Frequency of Liver Biopsy prior to treatment in HCV (%)

 

Never

Rarely

Some-
times

Most
often

Always

Genotype 1

0

2

13

45

41

Genotype 3

3

28

38

19

12

Normal
ALT
and AST

2

10

37

30

21

Imaging
meeting
criteria for
cirrhosis

18

40

22

12

8

 


HCV Treatment – PegIntron

 

1282. Effect of Interferon alfa-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis. 

M. Kurokawa; N. Hiramatsu; T. Takehara; T. Oze; T. Yakushijin; T. Igura; K. Mochizuki; K. Imanaka; M. Oshita; H. Hagiwara; E. Mita; T. Hijioka; Y. Inui; K. Katayama; H. Yoshihara; Y. Imai; M. Kato; S. Kiso; T. Kanto; A. Kasahara; N. Hayashi

 

Background & Aim:

IFN therapy is effective in reducing hepatocarcinogenesis and in improving survival rate of patients infected with hepatitis C virus (HCV). The combination therapy using IFN alfa-2b plus ribavirin is a more effective treatment to eradicate HCV than IFN monotherapy. However, it has not been accurately evaluated whether the combination therapy could reduce HCC development in patients infected with HCV or not. The objective of this study was to elucidate a long-term effect of a combination of IFN alfa-2b plus ribavirin therapy and to clarify whether this therapy can reduce HCC in patients with chronic hepatitis C.

 

Patients & Methods:

This study was conducted at Osaka University Hospital and institutions of participating in the Osaka Liver Forum. A total of 403 patients infected with HCV were enrolled in a multicenter trial. There were 257 men and 145 women with mean age of 55.8 ± 10.9 years. 100 patients had severe fibrosis (F3-4) in the liver. The median observation period for all patients was 36.5 ± 14.8 months with a range of 6 to 62 months from end-point of IFN treatment. All patients were treated with a combination of IFN alfa-2b plus ribavirin therapy. Transient response was defined as negative HCV-RNA in the serum at the end of treatment but detectable at 24 weeks after completion of therapy. We examined the incidence of HCC after a combination therapy and analyzed the risk factors for liver carcinogenesis.

 

Results:

One hundred thirtynine patients (34%) of all achieved a sustained virological response (SVR). The cumulative rate of incidence of HCC was significantly lower in patients of SVR than in those of non-SVR (P=0.03), while there is no difference in the cumulative incidence of HCC between transient response group and no response group. Cox proportional hazard analysis indicated following risk factors as independently significant which were related to development of HCC: age was > 60 years (P = 0.006), histological staging was advanced (P = 0.033), non-SVR to IFN therapy (P = 0.044). In addition, the cumulative incidence rate of HCC was significantly lower in patients who had average serum ALT levels of < 40 IU/L than in those who showed average serum ALT levels of ≥ 40 IU/L after the combination therapy irrespective of viral eradication (P=0.021).

 

Conclusions:

·        The attainment of SVR or continuous normalization of ALT levels after IFN therapy is effective in reducing HCC development.

·        Old age, severe fibrosis and non-SVR were independent significant risk factor contributing to HCC development.

 


HCV Treatment – Side Effects

 

1284. Central Hypothyroidism in patients with chronic hepatitis C. 

D. E. Zantut-Wittmann ; M. P. Pavan; E. J. Pavin; F. L. Gonçales Junior

 

Introduction:

Thyroid dysfunction is described during the treatment of virus C chronic hepatitis (HCV) with Interferon (IFN). Some authors referred panhypopituitarism or central hypothyroidism during this therapy.

 

Objective:

The objective was to relate the prevalence of central hypothyroidism in HCV patients before and after IFN therapy.

 

Methods:

We evaluated the thyroid function of 328 HCV patients, followed from 2001 to 2007 in a Brazilian reference center to HCV and treated with standard IFN (IFN) and/or pegylated-interferon (PEG) associated to ribavirin. Levels of free thyroxin (fT4) and thyrotropin (TSH) were measured before, each 3 months under treatment and after withdrawal the medication. The diagnosis of central hypothyroidism was considered when the serum levels of fT4 were lower of the reference values with concomitant normal or lower TSH levels verified at least in 2 consecutive measures. Twenty patients that presented primary hypothyroidism or hyperthyroidism were excluded.

 

Results:

Among the 308 patients evaluated, with mean of age of 43.9 years, 72.7% were men; 87.0% were Caucasoid. Eighteen patients (5.8%) presented central hypothyroidism (11 men; 7 women) before-treatment. During the treatment 12 patients maintained laboratorial changes, 3 became euthyroid (2 women; 1 man) and 3 women developed primary hypothyroidism. During treatment, 17 new patients (12 men; 5 women) developed central hypothyroidism. Of the 29 patients (9.4%) (22 men, 7 women) with central hypothyroidism, 11 used IFN; 6 PEG, 12 patients used 2 or more therapeutic schedules and 71.4% did not reach sustained viral response. Virus C genotype 1 was found in 63% of them. Among these patients, the comparative analysis showed that the gender, age, cirrhosis, viral genotype, duration of treatment and the type of interferon used were not statistically significant. The absence of sustained viral response was associated to the presence of central hypothyroidism (p=0.015; OR=3,83; IC95%=1.21-12.12).

 

Conclusion:

In conclusion, this preliminary study suggests that the HCV patients may develop central hypothyroidism due the viral infection, because in some cases the diagnosis was made before treatment. In accordance to the literature, the treatment with interferon triggered central hypothyroidism. Additionally, in this study, these patients presented 3.83 times more chance to not obtain sustained viral response. Panhypopituitarism must be investigated for the proper hormone replacement.

 


HCV treatment – IDUs

 

1286. Specific joint hepatology–addiction medicine follow-up of hepatitis C treatment for intravenous drug users (IDU) or ex-IDU improves treatment response. 

G. Anne; G. Laurent; B. Vincent; A. Jean-Pierre; B. Celine; J. Jacques

 

Background:

Since 2002 in France, 80% of new hepatitis C virus (HCV) infections have resulted from sharing injection materials. Our goal was to evaluate the impact of joint hepatology–addictive medicine treatment and follow-up for IDU or ex-IDU HCV-infected patients.

 

Methods:

The medical files of 176 consecutive patients, who consulted for hepatitis C between September 2006 and March 2007, were retrospectively assessed. Baseline information on demographic patterns, sources of infection, biological, virological and histological parameters were collected. Type of treatment, outcomes, tolerance and compliance were analyzed.

 

Results:

Among the 176 patients, 85 were infected through drug-injecting materials (IDU group) and 91 through other sources (non-IDU). The groups were comparable in terms of demography, but 64/85 patients in IDU group were co-infected with HIV versus 31/91 in non-IDU group. Mean serum HCV RNA was at 6.2 log UI/ml in IDU group versus 5.8 log UI/ml in non-IDU group. In IDU group, HCV was genotype 1 in 53% (45 pts) patients, genotype 2 or 3 in 27% (23 pts), genotype 4 in 6% (5 pts), not known in 14% (12 pts). In non-IDU group, HCV was genotype 1 in 52% (47 pts), genotype 2 or 3 in 10% (9 pts), genotype 4 in 31% (28 pts), not kwon in 6% (7 pts), one patient was infected by HCV genotype 5 in the non-IDU group. In IDU group 37/85 (43%) had a severe liver disease (metavir score F3 or F4) versus 31/91 (34%) in non IDU group. 28 IDU patients were medically managed by joint hepatology–addiction follow-up (IDU-J), 22 required treatment, 21 accepted it. IDU-J and non-IDU had similar treatment response with, respectively, 53% and 52% end of treatment response and 45% and 38% sustained virological response. In contrast, among 57 IDU patients not benefiting from joint follow-up for their hepatitis C (IDU–non-J), 43 required anti-HCV treatment, 34 accepted it. Outcome was poorer : 20% of sustained virological response. IDU-non-J were more likely not to complete treatment and not to have adherence to treatment.

 

Discussion:

·        Despite poorer predicting factors of virological response in IDU patients than non-IDU (HIV infection and severe liver disease), IDU-J but not IDU-non-J had similar adherence to treatment and virological response.

·        This result suggests that hepatology-addiction joint follow up could improve access and success of anti-HCV treatment.

 


HCV Treatment – General

 

1290. A retrospective comparative study of Pegylated interferon and ribavirin for the treatment of chronic hepatitis C genotype 6 and genotype 1.

O. T. Tsang; J. Zee; J. Chan; R. S. Li; J. Lai; T. S. Lai

 

Introduction:

The predominant genotypes for HCV infected persons in Hong Kong are 1 and 6. However, there has not been any local study performed for combination pegylated IFN- alpha & Rib therapy for patients infected with HCV genotype 6 in Hong Kong. A retrospective review is thus undertaken so as to fill this gap.

 

Methods:

All patients with chronic hepatitis C genotype 1 and 6 treated with subcutaneously pegylated interferon (IFN) injection (Pegylated IFN alpha-2a at dose 180 µg or pegylated IFN alpha-2b at 1.5 µg per Kg body weight weekly) and oral Ribavirin at dose 800-1200mg daily for 48 weeks at the Infectious Diseases clinic in the Princess Margaret Hospital in Hong Kong is conducted. Inclusion criteria include Antibody to HCV with detectable serum HCV RNA, HCV genotypes 1 or 6, and persistently elevated ALT levels for more than 6 months. Patients with history of autoimmune hepatitis, major psychiatric illnesses, drug-induced or alcoholic hepatitis, infection with hepatitis B virus or human immunodeficiency virus, decompensated liver diseases, severe renal, cardiac or pulmonary diseases, unstable thyroid dysfunction, previous IFN therapy & pregnancy were excluded.

 

Assessment of efficacy:

HCV genotypes were determined prior to treatment and HCV quantitation tests were checked prior to, at 12 weeks into treatment, end of 48 weeks treatment and 24 weeks after completion of treatment. The end of treatment response (EOT) is defined as undetectable serum HCV RNA at the end of the 48 weeks treatment. While the sustained virological response (SVR) is defined as undetectable serum HCV RNA 24 weeks after the discontinuation of treatment. Early virological response (EVR) is defined as a greater than 2-log decline in or undetectable serum HCV RNA at week 12 of treatment.

 

Results:

A total of 65 patients were included with 36 male and 29 female. Their mean age was 52 with range from 26 to 69. HCV infection was acquired by blood transfusion in 76.5%. There were 44 patients having genotype 1 and 24 patients with genotype 6. The mean alanine transaminase levels were 136.7 U/L and 120U/L for genotype 1 & 6 respectively. The mean initial HCV RNA levels were 1819193 & 936200 IU/ml for genotypes 1 & 6 respectively. By intention-to-treat analysis, the EVR for genotype 1 and 6 were 58.5%  & 79.2% (p = 0.09) and the EOT were 56.8% & 79.2% (p = 0.09) respectively. The SVR for genotypes 1 & 6 were 48.8% and 62.5% (p = 0.284) respectively.

 

Conclusion:

In Hong Kong, China, genotype 6 has similar virological response to that of genotype 1 to combined pegylated interferon and ribavirin treatment.

 


HIV/HCV Coinfection

 

1291. HIV/HCV Co-Infected Virologic Responders To Pegylated IFN And Ribavirin Therapy More Frequently Suffer IFN-Related Adverse Events. 

A. Osinusi; J. J. Rasimas; R. Bishop; M. McLaughlin; M. A. Polis; H. Masur; S. Kottilil

 

Introduction:

HIV/HCV coinfected patients have higher rates of substance abuse, psychiatric disorders, HAART toxicities including anaemia at baseline than HCV monoinfected patients, rendering these patients at higher risk of interferon [IFN] related side effects. We evaluated the relationship between IFN related side effects and HCV virologic response in HIV/HCV coinfected individuals on therapy.

 

Methods:

55 HIV/HCV coinfected patients treated for 48 weeks with peg IFN α-2b or peg IFN α-2a in combination with ribavirin were prospectively studied. HCV RNA [Bayer bDNA v.3], safety labs and immune profiles were measured frequently. Psychiatric and ophthalmologic evaluations [visual acuity and fields, color vision and indirect opthalmoscopy] were performed at baseline and at regular intervals. Psychiatric toxicities were defined as emergent or worsening psychiatric symptoms from baseline incorporating DSM-IV criteria, BDI scores and medication changes. The t-test was used for comparisons between groups while a mixed model analysis was used to evaluate the relationship between HCV viral load decline and CD4 counts.

 

Results:

HCV responders were more likely to have IFN related psychiatric toxicities than non-responders, 63% vs. 7.7%, (p-value =0.009). The Table shows relationships for other parameters. A mixed model analysis produced a highly significant positive slope for the relationship between HCV viral load decline and changes in CD4 counts (slope 1.12, p-value=0.0001). Overall 56% of responders compared to 35% of nonresponders had at least 2 classes of IFN related toxicities( p-value =0.227). Ten patients discontinued study medications between Day 5 and Week 16; 40% had achieved viral suppression or >2 log HCV viral load decline at the time of discontinuation.

 

Conclusions:

HIV/HCV co-infected patients responding to HCV therapy were more likely to experience IFN related side effects, particularly psychiatric symptoms. These data emphasize the need for patients with IFN-related side effects to be supported through treatment in a multidisciplinary setting as these patients are more likely to achieve a cure. Future studies will evaluate the relationship between occurrence of serious IFN-related adverse events and HCV virologic response as well as factors that predict the development of IFN-dependent adverse events.

 

Table: Prevalence of side effects

Toxicity

All patients
[%]

Responders
[%]

Non responders
[%]

p-value

Psychiatric toxicities attributed to IFN

50%

63%

7.7%

0.009

Opthalmologic toxicities attributed to IFN

38.2%

41%

28.6%

0.528

Anaemia [Hgb <10] or use of erythropoeitin

36.4%

36%

35.7%

0.748

Neutropenia [ANC<1000] or use of G-CSF

43.6%

41.5%

50%

0.756

 


HCV Treatment – Pegasys

 

1295. Sustained Virologic Response Is Associated With Worse Qol During And Improved Qol After Treatment With Peginterferon Alfa-2a And Ribavirin. 

M. von Wagner; W. Hofmann; G. Teuber; T. Berg; T. Goeser; U. Spengler; H. Hinrichsen; H. Weidenbach; G. Gerken; M. P. Manns; P. Buggisch; E. Herrmann

 

Background and aims:

Chronic hepatitis C is associated with impairment of quality of life (QOL). In the present study, QOL was frequently assessed before, during and after antiviral treatment with amantadine or placebo, administered in combination with peginterferon alfa and ribavirin. Aim of the study was to evaluate the impact of amantadine and virologic response on QOL.

 

Methods:

Seven-hundred-four untreated HCV 1-infected patients received amantadine-sulphate or placebo in combination with 180µg peginterferon alfa-2a once weekly and ribavirin (1000-1200mg/day) for 48 weeks in a multicenter, placebo-controlled trial (Hepatology, in press). End of treatment (ETR) and sustained virologic response (SVR) after a 24 week follow-up period were assessed by qualitative RT-PCR (sensitivity 50IU/mL). Quality of life was assessed at screening, week 12 and 48 of therapy, and week 24 of follow-up, respectively, by a validated German questionnaire related to the SF-36 Health Survey. QOL was evaluated according to former established standardized criteria for QOL assessment in patients with chronic hepatitis C and differences were assumed as clinically signifcant with an effect size (ES) > 0.2. Statistical significance was assessed by Fisher exact test and Van Elteren test.

 

Results:

ETR and SVR rates were similar between both treatment groups. No impact on QOL was found for amantadine. However, clinically and statistically significant differences were found between patients who achieved SVR and patients who did not. Patients who achieved SVR had higher clinically significant mean levels in the domain “role physical” and the “physical composite score” before treatment. At week 12 of combination therapy, SVR patients had clinically and statistically significant higher drops of mean level in the domains “physical function”, “vitality”, “role emotional”, and the “physical composite score” as compared to non-SVR patients. At the end of follow up, SVR patients showed clinically significant higher mean levels in 7 of 8 domains and in the “physical composite score” than non-SVR patients.

 

Conclusion:

·        In the present large multicenter study, in patients who achieved SVR clinically significant more impairment in quality of life was observed during treatment, although, their QOL before treatment was found to be better as compared to non-SVR patients.

·        At the end of follow up, QOL was found to be significantly better in patients who achieved SVR than in patients who did not.

 


HCV Treatment – IDUs

 

1297. Impact of Recent Substance Use on Antiviral Treatment for Chronic Hepatitis C. 

A. Knott; E. Dieperink; J. Durfee; S. B. Ho

 

Introduction:

Substance use is a common problem among patients with chronic hepatitis C virus infections (HCV). However, few studies have determined the impact of integrated care mental health/medical care on antiviral treatment outcome in patients with recent drug use and HCV.

 

Purpose:  

To determine the impact of recent substance use on antiviral treatment initiation in patients with chronic hepatitis C in an integrated hepatitis clinic.

 

Methods

Retrospective chart review of  300 consecutive veteran patients with chronic hepatitis C with an initial appointment in the hepatitis clinic between 1/1/05 and 4/9/07 who were screened with a drug-use questionnaire (DUQ) (heroin, cocaine, cannabis, amphetamines, LSD, and Ecstasy), an alcohol screen (AUDIT-C), the Beck Depression Inventory (BDI) and a Urine Drug Screen (UDS). Antiviral treatment initiation and viral response were obtained through 9/30/08. Patients with positive screens were referred to a co-located mental health clinician who managed the patient or coordinated care with current mental health providers.

 

Results:  

Most patients were male (96.6%), mean age was 53.3 years, mean BDI was 13.7 (BDI≥10 mild depression), mean AUDIT-C was 4.0 (≥4 hazardous alcohol use), 92.8% reported lifetime drug use with 33.9% reporting misuse of prescribed medications and 33.9% reported substance use in the last 6 months. The UDS was positive for amphetamines, benzodiazepines, cannabis, cocaine, or opiates in 31.7% of patients. Among those with substance use during the last 6 months 57.6% used marijuana only, 33% cocaine, amphetamines 9.1%, benzodiazepine (7.6%) alcohol (7.6%) opiates 4.5%,and  oxycodin (1.5%).  To date 116/292 offered treatment; 62/116 have begun antiviral therapy.  Patients without recent substance (no self-reported drug use and AUDIT-C<4) use were more likely to initiate antiviral treatment.  A total of  out of 30 patients (30%)  in the group who did not report taking drugs achieved an SVR compared to 9 out of 32 patients (28.1%)  in the group who reported taking drugs/alcohol. 

 

Conclusions:  

·        Lifetime drug use is common in this cohort and1/3 of patients report misuse of prescribed narcotics, benzodiazepines or stimulants in their lifetime indicating that clinicians should closely monitor narcotic prescribing.

·        Despite the high rate of recent substance use, many patients started antiviral therapy and SVR was not diminished.

·        Integrated care services provided in a hepatitis clinic may enhance access and antiviral treatment outcomes in this difficult to treat population.

 


HIV/HCV Coinfection

 

1299. High sustained virological response to peg-interferon and ribavirin in HIV-HCV co-infected patients: "real life" single center experience. 

E. Veitsman; S. Edoardo; G. Hassoun; M. Lorber; K. Maor; R. Kramskay; S. Pollack; Y. Baruch

 

Background and aim:

Recently with the emergence of highly effective ART, chronic liver disease has become the leading cause of morbidity and mortality in co-infected HIV-HCV patients. The overall SVR rate in this population remains unsatisfactory. The aim of this study was to evaluate the response to Peg-interferon and Ribavirin therapy in HIV-HCV co-infected patients in a single center in the real life.

 

Patients and methods:

Consecutive HIV-HCV co-infected patients were completely evaluated in the liver clinic. Liver needle biopsy as a part of the evaluation was performed in 100% of the patients. The patients were treated by multidisciplinary team consisting of immunologists, hepatologists, social workers, nurses with close follow- up. 48 weeks duration of Peg-Interferon and Ribavirin combination was used for all genotypes according to the recent Guidelines. Weight adjusted Ribavirin doses were applied for all genotypes. The treatment was started after stabilization of HIV parameters and successful weaning from drug and alcohol addiction.

 

Results:

Out of 122 HIV HCV coinfected patients, 64 were fully evaluated . Six patients had spontaneous viral clearance and 9 are still under treatment. 28 (75 % male) completed treatment. Of those 18 (64%) achieved SVR. Out of 13 Genotype 1 patients 8 (62%) achieved SVR. In 15 Non-one Genotype patient the SVR rate was 67% (10 of 15 patients). 5 patients were defined as relapsers and non-responders . 3 patient developed breakthrough under the treatment. In 2 patients the treatment was discontinued due to severe adverse events.

 

Overall adherence to the treatment was high.

 

Conclusions:

·        Measures, such as the use of multidisciplinary approach, high adherence of physicians to the Guidelines, weight based Ribavirin dose, and selecting patients who are ready to start therapy can significantly improve SVR rate in this difficult-to- treat patient population.

 


HCV Treatment – Side Effects

 

1300. Autoimmune Thyroid Disease In Chronic Hepatitis C Treated With Peg-IFN And Ribavirin: Prevalence, Incidence And Influence On Therapeutic Outcome In 4498 Naive Patients. 

F. Morisco; M. Tartaglione; A. De Luna; P. Andreone; C. Coppola; N. Passariello; C. Carella; A. Scuteri; C. Iannacone; M. Sarracino; N. Caporaso

 

Background:

Autoimmune thyroid disorders have been reported as side effects of interferon therapy in patients with chronic hepatitis C, although there are still controversial data regarding the incidence, the risk factors and the correlation with therapeutic response.

 

Methods:

4498 naives patients were consecutively enrolled in the PROBE : an observational study involving 167 Italian centers consisting of a retrospective and a prospective phase designed to assess the efficacy and safety of pegylated interferons plus ribavirin in a non selected population of patients with chronic hepatitis C. All were tested for clinical, biochemical and virological parameters and for thyroid antibodies (TgAb and TPOAb) before, 6 and 12 months after the beginning of treatment (PEG-IFNs and Ribavirin) and 6 months after the end of therapy.

 

Results:

274/4498 (6,1%) patients were positive for antithyroid antibodies before antiviral therapy. During treatment 248/4224 (5,9%) patients showed de novo appearance of antibodies. On the whole, 522 patients (11,6%) were affected by autoimmune thyroid disease (ATD). The principal demographic, virological and histological characteristics were not statistically different in patients with and without ATD whereas the prevalence of female and BMI ≥ 30 were higher in the ATD group than in the non-ATD group (respectively 52,8% vs 36,1% p< 0.0001; 14,6% vs 8,9% p< 0.0001).

 

From a clinical point of view the overall percentage of sustained virological response was similar in patients with (53,8%) and without (52,1%) ATD.

 

Conclusions:

Incidence of ATD in HCV patients, who were exposed to PEG-IFNs and Ribavirin, was low; ATD was related to gender and obesity and does not seem to affect outcome to antiviral therapy.

 


HCV Treatment – Predictors of Treatment Response

 

1301. Relationship between insulin resistance (IR) and sustained virologic response (SVR) in the treatment of Hepatitis C virus (HCV) with interferon and ribavirin. 

W. M. Cassidy; R. Horswell

 

Purpose:

To determine if a relationship exists between central obesity and/or insulin resistance (IR) and sustained virologic response (SVR) in the treatment of HCV with interferon and ribavirin.

 

Methods:

Four-hundred Hepatitis C positive patients were enrolled in a multi-center study to evaluate the relationship between IR (measured by the HOMA score), waist hip ratio and sustained virologic response (SVR). Inclusion criteria was HCV RNA positive, age >= 18 years old, and an elevated ALT on at least one occasion. Exclusion criteria included diabetes (defined as fasting blood glucose (FBS) >=116 or use of medications used to treat diabetes), being HIV positive and secondary causes of liver disease aside from obesity. All patients had a liver biopsy within 2 years of entry. Waist hip ratio (WHR), FBS, fasting insulin level (FIL), ALT, AST, and a HCV RNA quantitative were measured at baseline, 12, 24 36, 48 and 72 weeks. Initially all genotypes were enrolled, but subsequently only genotype 1 (GT 1) patients were enrolled and included in final analysis.

 

Results:

In the final analytical sample of 2890 subjects, 33% were female and 33% were African-American; a median age of 46 years. The table shows both unadjusted and adjusted odds ratio (OR) estimates for HOMA score terciles from logistic regression analyses in which SVR (at 72 weeks) was the dependent variable. The adjusted effects are from a model that also included BMI, stage, baseline RNA level, gender, and race. The p-values are from a test of a null hypothesis of no relationship between HOMA and SVR versus an inverse monotonic relationship. In both the unadjusted and adjusted models, the effect estimates are monotonic, but statistical significance is only achieved (at α=0.10) in the unadjusted model.

 

In the adjusted model, race had a clear relationship to SVR, with an OR (for African-American versus all other race categories) of 0.36, p = .002. However, it is difficult to distinguish with confidence among possible independent effects for HOMA score, fibrosis stage, and obesity.

 

Conclusion:

·        Lower HOMA scores were associated with a higher probability of virological response

·        BMI, baseline RNA, age, and female gender did not significantly influence virological response

·        Insulin resistance and race independently influenced the likelihood of virological reasponse. 

 


HCV Treatment – RibaPak

 

1302. Treatment compliance in patients taking RibaPak® or 200mg ribavirin: Preliminary analyses from the ADHERE registry. 

V. K. Rustgi; I. Alam; B. Cecil; A. D. Tice ; T. Stainbrook; K. D. Ingram; K. David

 

Background:

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States (US). Current standard of care treatment is combination therapy of pegylated interferon (PIFN) plus ribavirin. Poor compliance to treatment is an important cause of treatment failure. Treatment compliance is complicated by the fact that traditional ribavirin (RBV) treatment is associated with a significant daily pill burden. RibaPak® (RBP), the first 400mg and 600mg ribavirin tablets, offers simplified dosing at 2 pills a day vs. up to 6 a day with RBV.

 

Aims:

To evaluate if treatment compliance is improved in patients prescribed RBP vs. RBV.

 

Methods:

Accurate Dosing in Hepatitis C: Examining the RibaPak® Experience (ADHERE) is a multi-center, prospective, observational registry capturing data on compliance with RBP vs. RBV in patients with HCV in the US. Patients are followed for 24 weeks while on either RBP or RBV therapy, in conjunction with weekly PIFN. Compliance is measured by patient’s self-reported pill counts at treatment week 4, 12 and 24.

 

Results:

As of June 2008, 508 patients have been enrolled from 38 sites; 95 patients (RBP = 67, RBV = 28) had 4 week compliance data available and are included here. Patients’ mean age was 48.2 years; 58% were male and the majority (71%) Caucasian. At 4 weeks, RBP patients had taken an average of 98% of the total prescribed doses and RBV patients had taken an average of 95% of the total prescribed doses. Missed doses translated into RBP patients taking an average of 22.1 mg per day less than prescribed and RBP patients taking an average of 49.7 mg per day less than prescribed (p=0.21). Six month follow-up data were only available on a limited number of RBP (n=24) and RBV (n=4) patients but suggest that the number of doses missed in the RBV group may increase over time (% of prescribed doses taken at 24 weeks, 96% vs. 66% for RBP and RBV respectively).

 

Conclusions:

These preliminary data suggest potential differences in compliance between treatment with RBP and RBV. Future analyses will reveal if the trend observed in these data will continue, and become more robust, over the 24 weeks of the study. Based on these analyses, RBP may be a treatment alternative to RBV that can improve treatment compliance, and by extension, ultimately, treatment outcomes.

 


HCV Treatment – IDUs

 

1305. Three year follow-up of a multidisciplinary care and peer support model for the engagement of IDUs in care and treatment for HCV infection. 

J. Grebely; E. Knight; T. Ngai; K. Genoway; F. Duncan; M. I. Viljoen; M. Storms; D. Elliott; J. D. Raffa; B. Conway.

 

Purpose:

To evaluate engagement in HCV care and treatment for HCV infection among IDUs attending a weekly peer-support group at a multidisciplinary community health clinic.

 

Methods:

From March 2005 to March 2008, patients interested in receiving HCV treatment were referred to a weekly peer-support group and evaluated for treatment readiness/eligibility. Engagement in HCV care was defined as being under evaluation for HCV treatment, treatment not being medically indicated and having received HCV treatment, while subjects lost to follow-up were considered not engaged in HCV care. Patients received directly observed therapy with PEG-IFN alfa-2a or alfa-2b, in combination with self-administered RBV. Factors associated with engagement in HCV care were evaluated. End of treatment (ETR) and sustained virologic response (SVR) were also evaluated among those having completed therapy.

 

Results:

Overall, 204 subjects were referred over 3 years. Of these, 94 (47%) were lost to follow-up, 14 (7%) initiated or completed treatment for HCV infection prior to attending the group, 9 (4%) were under evaluation for treatment and treatment was deferred or not indicated in 30 (15%). Uptake of HCV treatment was 28% (n=57). The median number of group visits in subjects engaged in HCV care (n=110, 20 visits) was significantly higher than that in those not engaged (n=94, 1 visit, p<0.001). In multivariate analysis, attendance to group was significantly associated with subsequent engagement in HCV care; attended 2-4 visits (AOR 4.36; 95% CI, 1.47-12.91, P=0.008), 4-10 visits (AOR 9.15; 95% CI, 3.01-27.77, P<0.001) and >10 visits (AOR 81.34; 95% CI, 25.61-258.35, P=0.041), respectively. Age, sex and day of support group attended were not associated with engagement. Of 53 initiating treatment (mean age 48 years, 87% male), 44 and 9 received PEG-IFN alpha-2a and -2b, while 30 were genotype 1 (57%). Twenty were receiving methadone (38%) and 6 were HIV co-infected (11%). At baseline, 13 (25%) were actively using illicit drugs and the median drug abstinence was 2.5 months. Among subjects having completed therapy (n=19, genotypes 2 or 3: n=9), ETR and SVR were 63% (12/19) and 47% (9/19), with 78% (7/9) genotype 2/3 patients achieving an SVR. This occurred despite illicit drug use during treatment in 68% (13/19), with 69% (9/13) using weekly or less.

 

Conclusion:

A high engagement in HCV care and response to therapy can be achieved among IDUs attending a peer-support group. HCV support group attendance provides an important predictor of individuals more likely to engage in HCV care and may constitute a screening tool to identify those eligible for therapy.

 


HCV Treatment – Side Effects

 

1309. Importance of prior psychiatric consultation in pegylated interferon and ribavirin combination therapy for chronic hepatitis C. 

K. Kuhara; T. Ide; N. Uchimura; R. Kumashiro; T. Arinaga; K. Ogata; R. Kuwahara; I. Miyajima; M. Sata.

 

Background and Aims:

In pegylated interferon (PegIFN) and ribavirin combination therapy for chronic hepatitis C, various kinds of psychiatric side effects often occur, and some patients discontinued the IFN therapy due to psychiatric side effect. Therefore we performed many institutions collaboration research to verify whether psychiatric consultation before PegIFN and ribavirin combination therapy contributes to completion of that therapy.

 

Methods:

Five-hundred thirty five patients who started PegIFN-α-2b and ribavirin combination therapy in six hospitals affiliated with our hospital since January 2005 until August 2006 were included.

 

Patients were divided into two groups as follows, the group who have received psychiatric consultation before therapy as consultation group (N=223), the group who have not received psychiatric consultation before therapy except with a history of psychiatric diseases as non-consultation group (N=332).

 

We analyzed the rate of discontinuation by psychiatric side effect in these two groups.

 

Results:

The rate of discontinuation by the psychiatric side effect of the consultation group was significantly lower than that of the non-consultation group (1.8% (4/223) vs. 6.1% (19/312), P=0.035).

 

As the reason for the discontinuation of the therapy, the psychiatric side effect were 6.1% (4/65)in the consultation group and 27% (19/68)in the non-consultation group (P=0.0004).

 

In the patients who presented with the psychiatric symptoms during the PegIFN and ribavirin combination therapy, the rate of the therapy completion of the consultation group was significantly higher than that of the non-consultation group (69.2% (18/26) vs. 5.0% (1/20), P=0.0067).

 

In patients with a history of psychiatric symptom, the discontinuation by psychiatric side effect has not shown in the consultation group.

 

Conclusions:

Psychiatric consultation before PegIFN and ribavirin combination therapy contributes to complete that therapy.

 


HCV Treatment – Infergen

 

1310. Efficacy Of Daily Dose Consensus Interferon Alfacon-1(CIFN) And Ribavirin In Previous Non Responders To Pegylated Interferon and Ribavirin In Patients With Advanced Fibrosis From Chronic Hepatitis C. 

P. S. Mantry; M. Barnes.

 

Background:

At present, there are very limited treatment options for patients with Hepatitis C infection (HCV) who are non-responders or relapsers to combination treatment with pegylated interferon (PEG) and Ribavirin (RBV) combination. Our aim was to assess overall SVR using CIFN/RBV combination in a HCV patients with advanced fibrosis with previous exposure to PEG/RBV.

 

Methods:

Charts of 35 consecutive patients with HCV who were non-responders or relapsers after a course of pegylated interferon (alpha 2a/2b) combined with weight based ribavirin and were consequently treated with daily CIFN/RBV combination and completed 72 weeks of follow up were reviewed. Demographics, nature of previous response to therapy, disease severity, duration of treatment, use of growth factors and virologic end points were analyzed.

 

Results:

Demographics: 83% male, 69% Caucasian, 23% were African American, average age-55 years.

 

In terms of virologic characteristics, 91% patients had genotype 1; 3 patients had genotype 3. 31% patients were relapsers after PEG/RBV therapy, the rest were non-responders (defined as less than 2 log drop at 12 weeks or HCV RNA positive at 24 weeks by taqman/TMA PCR).

 

In terms of disease severity, 74% (26) patients had complete or incomplete cirrhosis on liver biopsy, 17% had moderate fibrosis and 5.7% patients had mild fibrosis.

 

All patients were treated with CIFN 15mcg SQ daily with weight based RBV (1000mg/day <75kg and 1200mg/day >75kg weight).

 

6 patients discontinued treatment due to severe treatment side effects. In 22 patients,treatment was discontinued at various time points (3,6 or 9 months) due to inadequate virologic response (failure to achieve 2log RNA drop at 3 months and PCR positivity thereafter).

 

Growth factors (erythropoietin, fligrastim) were used in 18 (51%) patients to avoid dose reductions. Yet, dose reductions in CIFN/RBV were done in 13 (37%) patients for severe hematologic suppression.

 

Of the remaining 7 patients who completed 1 yr of treatment 5 patients achieved a sustained virologic response(SVR) and 2 patients had a relapse in 72 weeks of follow up. Coincidently, all patients who achieved an SVR were previous relapsers to PEG/RBV.

 

Discussion:

1.     In our study, daily CIFN and weight based ribavirin produced an overall SVR of 14%. Furthermore, in PEG/RBV relapsers the SVR was 45%.

2.     Majority of these patients (92%) had significant fibrosis and even with growth factors, 37% required dose reductions and 17% discontinued treatment due to side effects.

3.     In our opinion, daily CIFN/RBV is a very viable treatment option especially for interferon sensitive HCV patients with advanced liver fibrosis who relapse after PEG/RBV therapy.

 


HCV Treatment – Substitute Opioid Therapy

 

1311. Pegylated Interferon Alfa-2a (Peg-2a) Plus Ribavirin (RBV) For Patients With Chronic Hepatitis C Virus (HCV) On Opioid Pharmacotherapy: Virological Outcomes, Psychological Impact And Safety. 

J. Sasadeusz; G. J. Dore; I. Kronborg; D. A. Barton; M. Yoshihara; M. Weltman.

 

Background and Aims:

HCV treatment uptake has been limited in people on drug dependency treatment due to concerns regarding efficacy, adherence and adverse effects, especially psychological effects such as depression and the inherent increased suicide risk. This study aimed to evaluate these parameters in patients receiving opioid pharmacotherapy

 

Methods:

Fifty-three patients at four Australian sites received Peg-2a 180 ug/week and RBV 800-1200 mg/day for 48 weeks (22 genotype 1(G1) or 24 weeks (31 G non1). HCV RNA was assessed at week 12 (EVR), end-of-treatment (ETR) and 24 weeks post-treatment (SVR). Depression was assessed using the Beck Depression Index (BDI II). Adherence was defined as taking 80% of both drugs for 80% of the planned duration.

 

Results:

Seventy-nine percent of patients were male, with a mean age of 37.9 years, 75% were receiving methadone and 25% buprenorphine, and 36 % had injected in the previous 6 months. Fifty one percent of patients had high viral load (>400,000 IU/ml) and 27% had F3/4 fibrosis.

 

Sixty-eight percent of G1 patients achieved EVR. SVR by ITT analysis was 36% for G1 and 71% for G non1 patients respectively. Twenty-five percent of patients injected during the treatment or post-treatment follow-up, with SVR of 63% among injectors and 53% among non-injectors, respectively. Only two patients relapsed, both G1, of which one was an active injector while the other was not. Sixteen patients (12 G1 and 4 G non1) withdrew prematurely from treatment: 5 due to safety and 11 due to non-safety reasons. Adherence to therapy was 59% for G1 patients and 84% for G non1 patients. There were no significant differences in mean BDI scores between or within groups at either beginning of treatment or at week 24

 

Conclusions:

HCV treatment of patients undergoing opioid pharmacotherapy has comparable efficacy to non-pharmacotherapy patients. There was good treatment adherence, no significant increase in depression and similar levels of withdrawals due to adverse events. Adherence was better in patients receiving 24-week therapy and post-treatment reinfection rates were low. HCV treatment should be considered suitable for patients on opioid pharmacotherapy including selected active injectors.

 


HCV Treatment – General

 

1314. Long-term efficacy of peginterferon with ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related advanced fibrosis. 

K. Chang; C. Lee; J. Wang; C. Hung; T. Hu; S. Lu.

 

Background:

To clarify the risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection and to investigate the effectiveness of pegylated-interferon (peg-IFN) and ribavirin therapy

 

Methods:

A total of 301 HCV- related advanced fibrosis patients receiving peg-IFN and oral ribavirin for 24 or 48 weeks were analyzed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis.

 

Results:

180 (59.8%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that non-genotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 32 (3-73) months, HCC developed in 20 patients with non-SVR and 12 with SVR (P = 0.008). The Kaplan-Meier method and log rank test showed that age 58 years (P < 0.001), low platelet count (<13x109/L) (P=0.001) and non-SVR (P = 0.005) were associated with HCC occurrence. Using Cox's regression analysis indicated that age 58 (odds ratio (OR) = 4.14, P = 0.003), non-SVR (OR= 3.521, P = 0.036), and low pretreatment platelet count (OR = 3.076, P = 0.004) were independent factors contributing to HCC development.

 

Conclusions:

This present study found that nongenotype 1b and low viral load were independent variables of SVR. Peg-IFN and ribavirin therapy significantly reduces the risk for HCC, especially among virologic responders in patients with HCV-related advanced fibrosis.

 


HCV Treatment – General

 

1317. Differences in Adherence to PEG-Interferon and Ribavirin Among Subgroups Perceived to be At-Risk for Non-Adherence. 

V. Lo Re; V. Amorosa; A. Localio; R. M. O'Flynn; V. Teal; Z. Dorey-Stein; J. Kostman; R. Gross.

 

Background:

Adherence to PEG-interferon + ribavirin is associated with early and sustained virologic response, but the factors associated with non-adherence to this regimen have been incompletely examined. These data can help determine the subgroups of HCV patients in which targeted adherence interventions may be warranted.

 

Objective:

To examine separately differences in adherence to PEG-interferon and ribavirin among patient subgroups during the initial 12 weeks of therapy.

 

Methods:

We conducted a cohort study among chronic HCV-infected veterans treated with PEG-interferon + ribavirin. Subjects were eligible if they had: 1) a quantitative HCV viral load prior to therapy; 2) at least one pharmacy refill of both PEG-interferon and ribavirin; and 3) quantitative HCV viral load at 12 weeks. Adherence to each medication was calculated using pharmacy refill data and could exceed 100%. We compared median adherence to PEG-interferon and ribavirin between subjects with and without the following characteristics: HIV infection; depression; post-traumatic stress disorder (PTSD); history of alcohol abuse; and employment. Adherence differences were compared using Wilcoxon rank-sum tests.

 

Results:

Among 188 eligible subjects, 15 (8%) were HIV-coinfected, 60 (32%) had depression, 22% had PTSD, 126 (67%) had a history of alcohol abuse, 56 (30%) were unemployed; and 65 (35%) were co-administered >5 medications. Subjects with HIV infection had higher median adherence to PEG-interferon (110% vs. 103%; p=0.01) and ribavirin (110% vs. 102%; p=0.3) compared to HIV-uninfected individuals. Subjects with a history of depression, post-traumatic stress disorder (PTSD), alcohol abuse, or unemployment did not have poorer adherence compared to those without a history of these conditions.

 

Conclusions:

1.     Subjects with a history of HIV, depression, post-traumatic stress disorder, alcohol abuse, or unemployment did not have poorer adherence compared to those without a history of these conditions.

2.     HCV providers should not be reluctant to initiate treatment in these patients because of a perceived risk of non-adherence.

 


Liver Transplantation – HCV Treatment

 

1318. Standard or pegylated interferon with or without ribavirin treatment of hepatitis C after liver transplant: a meta-analysis. 

G. K. Papazian.

 

Introduction & Aims:

Almost all hepatitis C virus (HCV) infected patients receiving liver transplants develop recurrent hepatitis C within the graft leadingto cirrhosis in 70% of these patients within five years. Our aim was to evaluate sustained viral response (SVR) from interferon (IFN)-containing regimens in post-transplant HCV patients.

 

Methods:

Searching Medline and Web of Science from 1966 to 2007, we included randomized controlled trials, uncontrolled studies, and meeting abstracts that reported outcomes for HCV transplant recipients treated with IFN or pegylated-IFN (PEG) alone or with ribavirin (IFN/RBV or PEG/RBV) for at least 48 weeks. To pool SVR, we used the DerSimonian and Laird random effects model on an intent-to-treat basis. We also examined the relapse rate and subgroups including genotype 1 only, type of IFN, type of PEG, and RBV dosing.

 

Results:

We identified 8 controlled trials (2 IFN, 2 PEG, 2 IFN/RBV and 2 PEG/RBV) and 55 uncontrolled studies (2 IFN, 3 PEG, 27 IFN/RBV, 23 PEG/RBV) consisting of 1749 patients, 75% male (range 44-93%), mean 52-years old (46-59). None of the # placebo patient achieved SVR. Each treatment had the following SVR: 1% (95% CI: 0-7%) for IFN (4 studies, n=96); 17% (CI 11-26%) for PEG (5 studies, n=104); 26% (CI 22-31%) for IFN/RBV (29 studies, n=949); and 34% (CI 29-39%) for PEG/RBV (25 studies, n=782).

 

The relapse rate for end of treatment responders were 80% (CI 44-96%) IFN (4 studies, n=96); 46% (CI 29-63%) with PEG (5 studies, n=104) ; 35% (CI 28-42%) with IFN/RBV (22 studies, n=630); and 32% (CI 25-41%) with PEG/RBV (22 studies, n=694).

 

For PEG and ≥800mg RBV (12 studies, n=467), SVR was 36% (31-41%), For PEG with <800 mg RBV (13 studies, n=315) , SVR was 32% (23-41%). For genotype 1, IFN/RBV (7 studies, n=237) had a pooled SVR of 27% (17-42%), and PEG/RBV (12 studies, n= 399) a pooled SVR of 29% (CI ). With IFN and ≥800mg RBV (21 studies, n=658), SVR was 24% (19-29%) and IFN with <800mg RBV (4 studies, n=89), SVR was 35% (18-58%).

 

PEG 2a/RBV (5 studies, n= 206) had a 36% (27-46%) SVR rateand PEG 2b/RBV (21 studies, n=611) had a 33% (28-39%) SVR rate.

 

Conclusions:  

PEG/RBV treatment of post-transplant HCV appears to be superior to the other antiviral treatment alternatives with a 34% SVR, but long-term follow-up data on survival and recurrence should be obtained.

 


HCV Treatment – General

 

1321. Effectiveness of Hepatitis C Treatment with Pegylated Interferon and Ribavirin in an Urban Patient Population. 

A. L. Bunim; J. Karlitz; H. Massoumi; E. Garcia; A. J. Thosani; A. Pellecchia; P. J. Gaglio; J. F. Reinus.

 

Introduction:

In randomized controlled trials of hepatitis C (HCV) therapy with pegylated interferon and ribavirin, intention-to-treat analysis has consistently demonstrated sustained viral response rates (SVR) of 54 to 63% (efficacy). Treatment results in clinical practice (effectiveness) may not be the same as efficacy. Studies have suggested poorer response rates to HCV treatment in African Americans and Hispanics.

 

Aim:

To assess effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, HIV-negative, US urban population with a high percentage of ethnic-minority patients.

 

Methods:

255 patients were treated between April, 2001 and June, 2006 in either the Faculty Practice (n=132; mostly Managed Care) or the Liver Clinic (n=123; mostly Medicaid) of the Albert Einstein College of Medicine, Bronx, NY. Patients received standard combination therapy based on genotype and fibrosis stage, and were followed for 24 weeks after treatment completion. Care decisions were made by a single experienced supervising physician; every effort was made to help patients’ complete treatment including psychosocial support and medications to ameliorate side effects. Treatment was discontinued in patients who missed two or more injections or consistently missed ribavirin doses. Clinical and demographic data were collected retrospectively. All data were analyzed with intention to treat.

 

Results:

The mean age of patients was 50 years: 60% male and 40% female; 58% Hispanic; 20% African American; 9% Caucasian; 13% other. Patients had at least one liver biopsy; 29% had cirrhosis. 68% of patients had Genotype 1 infection; the remainder Genotypes 2 or 3. Treatment results are shown in the table.

 

Conclusions: 

1.     Combination treatment with pegylated interferon and ribavirin is less effective in a US urban population than predicted by multinational phase-III controlled trials.

 

2.     More Medicaid than Managed Care patients were unable to tolerate HCV therapy.

 

3.     HCV treatment decisions in US urban patients should be based on conservative expectations for SVR, not on reported efficacy.

 

Group

SVR*

Dose Discontinue/Withdrew*

No Response*

Relapsed*+

Geno 1 (n=173)

14

40

24

22

Geno 2/3 (n=82)

37

34

6

23

Faculty Practice (n=132)

27

28

21

24

Liver Clinic (n=123)

15

47

15

23

Total(n=255)

21

38

18

23

Cirrhosis (n=73)

12

49

23

16

* % of patients in the group /+ Relapsed during treatment course or < 24 weeks after therapy completion

 


HCV Treatment – General

 

1325. Outcomes of Antiviral Therapy for Hepatitis C in Day to Day Clinical Practice. 

K. R. Muller; R. Wundke; R. K. Altus; A. Rodgers; A. J. Wigg.

 

Background:

Sustained virological response (SVR) rates from pharmaceutical registration trials of pegylated interferon and ribavirin for treatment of hepatitis C infection are usually quoted by clinicians to patients prior to commencing therapy. The aim of this study was to determine local SVR rates associated with the clinical practice of a large metropolitan Australian hospital.

 

Methods:

Patients treated with pegylated interferon and ribavirin at our institution between 2004 and 2007 were studied. SVR rates were analysed on an intention to treat basis. Patient care was shared between hepatologists and viral hepatitis nurses, usually without involvement of general practitioners. Pegylated interferon alpha-2a was used in all patients.

 

Results:

221 patients (68% male; 32% female; mean age 44 years) commenced antiviral therapy (40% genotype 1, 8% genotype 2, 51% genotype 3, 1% other genotypes). 49% of this cohort had difficult to treat disease on the basis of significant axis 1 psychiatric morbidity (73 patients) or advanced liver disease on the basis of liver biopsy or clinical assessment (35 patients). Dropout occurred in 31 patients (14%) largely due to side effects (29 patients) or loss to follow up (2 patients). Most common side effects leading to early cessation of treatment were psychiatric problems followed by cytopaenias. Early cessation of therapy due to non-response occurred in 20 genotype 1 patients. 170 (77%) patients completed treatment but 6 month post end of treatment PCR was not available for 17 of these patients, who were excluded from further analysis. Overall, 116 (57%) patients achieved a SVR. When analysed by genotype, SVR rates were 42% for genotype 1, 63% for genotype 2, and 69% for genotype 3. For patients who were treated per protocol, SVR rates were 61% overall, 42% for genotype 1, 83% for genotype 2 and 73% for genotype 3. Dose reductions occurred in 9% of patients, most commonly due to cytopaenias.

 

Conclusion:

·        Results from our institution are inferior to those reported in pharmaceutical registration trials, but compare favourably to results recently described by large US and European centres.

·        Differences in response rates may be explained by differences in proportions of difficult to treat patients and differences in resources available to patients during therapy.

·        It is important that treatment centres are familiar with their local results and that this is shared with patients during pre-treatment counselling.

 


HCV Treatment – Predictors of Treatment Response

 

1334. Does steatosis influence the effect of therapy and the progression of chronic liver disease caused by HCV? 

K. Tokushige; H. Noto; S. Yatsuji; M. Taniai; E. Hashimoto; K. Shiratori.

 

Introduction

Steatosis is frequently observed in chronic liver disease caused by hepatitis C virus (HCV). To confirm whether steatosis influences the effect of therapy and the progression of chronic liver disease caused by HCV, we compared chronic liver diseases by HCV with and without steatosis.

 

Method

One hundred fifteen patients with HCV-related chronic liver disease were investigated. Eighty-three patients had genotype 1 virus, and the others had genotype 2 virus. Liver biopsy was done in 91% of the patients. Patients with steatosis of >30% were defined as the steatosis group. In all patients, peginterferon plus ribavirin therapy was given.

 

Results

1.     We compared physical condition, laboratory data and histological features between the steatosis and non-steatosis groups. Multivariate analysis proved a) gender (OR 12.9, P=0.015), b) body weight (OR 1.12, P=0.007), c) liver fibrosis grade (OR 3.05, P=0.012), d) serum g-GTP (OR 1.01, P=0.014) as independent factors. Also, in severe fibrosis patients (F3-4), the frequency of steatosis was significantly higher (frequency of steatosis: 33.3% in F3-4; 11.8% in F0-2).

2.     We compared the factors between sustained and non-sustained responders. Multivariate analysis proved a) age (OR 1.07, P=0.029), b) body weight (OR1.10, P=0.014), c) diabetes (OR 15.5, P=0.007), d) serotype (OR 0.153, P=0.004) as independent factors. Steaosis was not proven as an independent factor of the effect of interferon therapy. But in 4 patients with genotype 1 and severe steatosis (>50%), all were non-responders.

 

Conclusion

There was a significant association between steatosis and liver fibrosis, suggesting that steatosis might influence progression in chronic liver diseases with HCV. In this study, there was no significant association between steatosis and the effect of IFN therapy. Nevertheless, more studies are needed, as diabetes, with a significant association with liver steatosis, is an independent factor of the effect of interferon therapy.

 


HCV Treatment – Substitute Opioid Therapy

 

1335. Psychopathological Changes and Quality of Life in HCV-Infected, Opioid-Dependent Patients During Maintenance therapy. 

A. Schaefer; H. Wittchen; J. Siegert; M. R. Kraus.

 

Background and Aims:

Psychopathological and particularly depressive symptoms are not only frequent complications in opioid dependent patients during maintenance therapy but also among patients with chronic hepatitis C virus (HCV) infection.

 

We examined in a naturalistic prospective-longitudinal design of opioid dependent patients in maintenance treatment with and without HCV infection (1) the frequency of psychopathological symptoms and syndromes, (2) changes occurring between baseline and 1-year follow-up, (3) the degree to which patients receiving antiviral treatment have an increased burden of psychopathological symptoms, (4) the degree to which IFN therapy is related to efficacy and tolerability of agonist maintenance treatment.

 

Methods

Data came from a multi-center, multi-stage epidemiological study (COBRA) of a nationally representative sample of 223 substitution physicians in Germany and a total of 2,694 of their maintenance patients. Analyses are based on (a) the total sample and (b) the subset of patients who completed the baseline and 12-month follow-up evaluation. HCV infection (HCV+/HCV-), IFN treatment (IFN+/IFN-) status and all clinical measures as well as outcome were assessed by physicians. Psychopathology and quality of life were assessed using the patients-rated BSI (Brief Symptom Inventory) and the EQ-5D, respectively.

 

Results

(1) At baseline, regarding mental health, most frequent ICD-10 diagnoses were depressive disorders (38.9%), personality disorders (19.6%), and anxiety disorders (15.9%). Overall, 65.3 % (712 of 1,091) of HCV positive patients had a diagnosis of at least one mental disorder.

 

(2) HCV+ patients showed a marked deterioration over time (baseline vs. FU) only in the BSI subscale somatization (P = 0.002). No significant change in BSI total index was observed. The frequency of the ICD-10 diagnosis “sleep disorders” almost doubled within the 12-month follow-up period in HCV+ patients (12.8 % at baseline; 24.1 % at follow-up; P < 0.01).

 

(3) IFN treatment in HCV+ patients had virtually no measurable effect on psychopathology (depressive and anxiety disorders). (4) IFN treatment did not impair efficacy or tolerability of drug maintenance therapy and was not associated with more severe courses of psychiatric symptoms in most domains assessed.

 

Conclusions

Findings suggest no increased risk of maintenance treatment in HCV+ patients for psychopathological syndromes. IFN treatment did also have no adverse effects on psychopathology nor poorer tolerability and efficacy of agonist maintenance treatment. Rather, both kinds of therapies might profit from each other in these patients.

 


HCV Treatment – Predictors of Treatment Response

 

1336. Insulin resistance, LDL cholesterol and results of hepatitis C treatment. 

M. Lebouvier; A. Minello; A. Poussier; B. Bouillet; V. Jooste; M. Guignard; J. Petit; P. Hillon.

 

Introduction:

Recent studies have found relationships between metabolic factors and response to antiviral treatment in hepatitis C patients. Some of these studies identified insulin-resistance (IR), others LDL cholesterol (LDL-C), as bad prognosis factors for antiviral therapy.

 

Aim:

The goal of this work was to study sustained virological response according to IR and LDL-C in hepatitis C patients.

 

Methods:

66 patients (40 males and 26 females) treated by associated pegylated interferon-ribavirin were studied. Virological response was defined as absence of viral replication 24 weeks after the end of treatment. All patients underwent pre-treatment lipid dosages and IR evaluation by HOMA test. Fibrosis was evaluated by liver biopsy in 55 patients and by non-invasive tests in 11 patients.

 

Results:

Mean age was 45.1 +/- 11.9, mean BMI 25.1 +/- 4.5. Genotype 1 was predominant (43 cases), then genotypes 3, 2 and 4 (16 cases, 6 cases and 1 case respectively). Global response rate was 58 % (38/66): 82 % for genotypes 2 and 3, versus 45 % for genotypes 1 and 4 (p=0.01). In univariate analysis, sustained response patients had lower BMI (24.1 +/- 4.1 versus 26.5 +/- 4.8, p=0.04), age (43 +/- 13 versus 48 +/- 7, p=0.03), and HOMA (2.2 +/- 2.7 versus 2.4 +/- 1.6, p=0.09) and higher LDL-C (1.13 +/- 0.30 versus 0.97 +/- 0.27, p=0.03) than non-responders patients. In multivariate analysis, only genotypes 2 and 3 (0.004), LDL-C (0.02) and BMI (0.04) remained correlated to sustained response. No correlation was found with fibrosis level.

 

Discussion-Conclusion:

In this study, LDL-C was the only metabolic parameter to be associated with sustained response. Physiologically, LDL-C is negatively correlated to LDL receptor (LDL-R) expression. Low LDL-C reflects a high level of LDL-R whose positive effect on virus hepatocyte penetration and replication has been recently demonstrated. These properties of LDL-R may explain the negative correlation found between HDL-C and response to treatment in HCV patients. In the event that this mechanism is indeed involved, the question of a possible negative effect of hypolipemic drugs like statins on antiviral treatment response should be posed.

 


HCV Treatment – General

 

1338. Management of Chronic Hepatitis C Patients with Schizophrenia: Should we treat? 

F. Barakat; E. Barber; D. L. Oliver; L. Petcharaporn; N. Karlen; L. M. Richards; E. Alpert; W. Perry; T. Hassanein.

 

Introduction:

Twenty percent of patients with Severe Mental Illness and about 8% of patients with Schizophrenia have Chronic Hepatitis C (CHC). Schizophrenia patients are 35 times more likely to have abused or depended on illicit drugs than the general population. We explored the management of CHC patients with Schizophrenia.

 

Methods:

This is a retrospective review of all CHC/Schizophrenia patients seen in a single tertiary Liver Center between 1997 and 2007. Of the 109 patients identified, 46 were excluded due to non-adherence to clinic visits; 51 patients did not receive Interferon treatment (Group A) and 12 were treated with Pegylated Interferon and Ribavirin (Peg IFN/RBV) combination therapy (Group B). A third group consisting of 12 CHC patients with no Schizophrenia (Group C) was matched to Group B by age, genotype, fibrosis, HIV status and type of HCV therapy. Demographics, past medical history, concomitant medications, Schizophrenia characteristics, CHC characteristics, adherence, social support and Peg IFN/RBV information were recorded.

 

Results:

The 109 patients had a mean age of 49.1 ± 8.4 years; 74.7% were male, 64% Caucasian, 72.1% were Genotype 1 and all had compensated liver disease. Barriers to Peg IFN/RBV: 64.9% of patients in Group B were not treated due to uncontrolled Schizophrenia, 29.7% due to patient related factors and 5.4% due to liver disease severity. Peg IFN/RBV Therapy: Only 50% of Group B patients reached end of treatment versus 91.7% in non-Schizophrenia matched group (Group C; p=0.03). The main reason for early discontinuation in Group B was drug related side effects. Sustained Virologic Response was achieved in 9.1% of Group B versus 50% in Group C (p=0.03). All patients experienced physical side effects and 66.6% had neuropsychiatric side effects. There were no differences between both groups in dose reductions, therapy interruptions or adherence.

 

Conclusions:

In CHC/Schizophrenia patients:

1.     the main barrier to Peg IFN/RBV therapy is uncontrolled Schizophrenia;

2.     IFN based therapy is possible provided psychiatric illness and medical co-morbidities are stable prior to treatment;

3.     Patient/caregiver education, preparation for treatment and establishing rapport to determine adherence and readiness for treatment is essential to improve treatment rates and success;

4.     CHC/Schizophrenia patients tolerate IFN based therapy well, adhere to treatment at similar rates to the matched comparison group; However, viral response is low in CHC/Schizophrenia patients.

In summary: management of CHC/Schizophrenia patients is possible, but requires a multidisciplinary approach.