Monday Poster Sessions, November 5, 2007

 

Topic: HCV Epidemiology – General

133. Chronic hepatitis C virus infection and risk of hepatocellular carcinoma: a community-based prospective study on 19,565 residents in Taiwan

M. Lee; H. Yang; C. Liu; S. You; P. Chen; C. Chen

 

Background and aims:

Chronic hepatitis C virus (HCV) infection is an important risk predictor of hepatocellular carcinoma (HCC). But the cumulative HCC incidence associated with chronic HCV infection has rarely been examined by community-based long-term follow-up studies. This prospective study aimed to evaluate the impacts of HCV on HCC in Taiwan, where chronic hepatitis B is hyperendemic.

 

Methods:

A total of 19,565 residents who were HBsAg-seronegative and free of liver cirrhosis or HCC at entry were enrolled during 1991 to 1992. There were 1,041 anti-HCV-seropositives and 18,524 anti-HCV-seronegatives. They were followed until December 31, 2004. The newly diagnosed HCC was ascertained through computerized data linkage with the national cancer registry profile. In total, 111 newly developed HCC were identified. Cox’s proportional hazards model was used to estimate multivariate-adjusted hazard ratio (HRadj) and its 95% confidence intervals (CI) for each risk factor included in the regression analyses.

 

Results:

During the follow-up of 246,154 person-years, the cumulative HCC incidence per 100,000 person-years was 26 for anti-HCV-seronegative participants, 290 for anti-HCV-seropositives with undetectable HCV RNA, 464 for anti-HCV- seropositives with detectable genotype 1 HCV RNA, and 370 for anti-HCV- seropositives with detectable genotype non-1 HCV RNA. Compared with anti-HCV- seronegative participants as the referent group, the HRadj (95% CI) was 8.0 (4.3-14.7) for anti-HCV-seropositives with undetectable HCV RNA, 6.6 (3.9-11.2) for anti-HCV-seropositives with detectable genotype 1 HCV RNA, and 6.2 (3.3-11.7) for anti-HCV-seropositives with detectable genotype non-1 HCV RNA after adjustment for age, gender, cigarette smoking and serum ALT level at study entry. The HRadj (95% CI) was 2.7 (1.7-4.1) and 7.6 (4.4-13.1), respectively, for serum ALT levels of 16-45 and >45 IU/L compared with ALT level <15 IU/L. Cigarette smoking was also associated with an increased HCC risk with an HRadj (95% CI) of 1.7 (1.0-2.8). In the stratification analyses, the age-gender-adjusted HRadj (95% CI) for the anti-HCV- seropositives with undetectable HCV RNA, anti-HCV-seropositives with detectable genotype 1 HCV RNA, and anti-HCV-seropositives with detectable genotype non-1 HCV RNA was 25.7 (7.3-90.9), 10.7 (3.3-34.6) and 11.3 (3.3-39.7), respectively, for those with ALT levels at entry >45 IU/L. The corresponding figures were 5.2 (2.2-12.0), 9.8 (5.3-18.2), and 7.5 (3.2-17.5) for those with ALT levels at entry < 45 IU/L.

 

Conclusion:

HCV infection, elevated serum ALT levels, and cigarette smoking are important HCC risk predictors for HBsAg-seronegatives in Taiwan.

 


Topic: HCV Epidemiology – IDU

134. Low uptake of treatment for hepatitis C virus (HCV) infection in a large community-based cohort of illicit drug users in Vancouver

J. Grebely; J. D. Raffa; C. Lai; M. Krajden; B. Fischer; T. Kerr; M. W. Tyndall 

 

Purpose:

To estimate HCV treatment uptake in a large community-based inner city cohort in Vancouver and compare this to the incidence of HCV infection over the period January 2000 to December 2004.

 

Methods:

CHASE is a cohort study of inner city residents recruited from January 2003 to June 2004. HIV and HCV status were determined through linkage with provincial databases. Treatment information was derived from the British Columbia Ministry of Health Pharmacare database (January 2000 to December 2004), which contains information on all HCV treatment prescriptions in the province. The incidence of HCV infection and the rate of HCV treatment uptake were calculated, expressed in terms of person-years of observation and compared over the follow-up period.

 

Results:

As of December 2004, among 3,553 subjects enrolled into the cohort, HCV antibody testing was performed in 2,117 and the HCV seroprevalence was 64.3% (n=1,361). In total, between January 2000 and December 2004, 15 HCV antibody positive subjects initiated treatment for HCV (1.1%), accounting for a total of 5420 person years of follow-up, yielding an overall treatment uptake of 0.3 cases per 100 person years (95% CI, 0.1-0.4). Overall, only 3 of 15 (0.2%) HCV antibody positive subjects achieved an SVR. During the same period, 91 HCV seroconversions were observed among a total of 1285 person years of follow-up, yielding an overall incidence of 7.1 cases per 100 person years (95% CI, 5.6-8.5). The incidence of HCV infection among recent injection drug users was 23.1 cases per 100 person years (95% CI, 17.5-28.5).

 

Conclusions:

We have documented extremely low rates of HCV treatment initiation and limited effectiveness of antiviral treatment for HCV, despite a high prevalence and incidence of infection in a large community-based cohort of inner city residents in Vancouver. Overall, the incidence of HCV was 24 times the rate of treatment uptake. Many studies have demonstrated that the treatment of this group is safe and effective, but the reality is that very few people in marginalized communities are accessing treatment for HCV. Given that the majority of new and existing cases of HCV occur in this group, efforts are urgently needed to expand programs for testing and treatment of HCV infection in illicit drug users.

 


Topic: HCV Epidemiology – HIV/HCV Coinfection

135. Liver-related mortality in human immunodeficiency virus-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (MORTAVIC 2005 Study in collaboration with MORTALITE 2005, ANRS-EN19)

E. Rosenthal; D. Salmon; C. Lewden; F. Bonnet; T. May; P. Morlat; M. François; C. Burty; E. Jougla; D. Costagliola; G. Chêne; P. Cacoub 

 

Objective:

To determine mortality due to end-stage liver disease(ESLD) and the profile of patients who died from ESLD in a nationwide population of HIV-infected patients and the evolution over a 10-years period.

 

Design and methods:

All departments of internal medicine and infectious diseases from the GERMIVIC Study Group prospectively recorded all deaths in HIV-infected patients during 2005. Fifty six departments, following around 35,000 HIV-infected patients, participated in the study. Results were compared with those of previous surveys conducted using similar methodology in 1995, 1997, 2001 and 2003.

 

Results:

Among 364 deaths documented during 2005, 142 (39.0%) were related to AIDS, 64 (17.6%) to ESLD, 55 (15.1%) to cancers neither related to HIV nor hepatitis viruses, 20 (5.5%) to cardiovascular diseases and 83 (22.8%) to other causes. Mortality due to ESLD represented 28.8% of non AIDS-related deaths. Patients dying from ESLD had chronic hepatitis due to virus C in 79.6% of cases and 46.6% of these patients had high alcohol consumption (> 30g/day)(table 1). In the Germivic survey, the proportion of ESLD-deaths has increased: 5% in 1995, 6.6% in 1997, 14.3% in 2001, 12.6% in 2003 and 17.6% in 2005, p<0.01. The proportion of hepatocellular carcinoma as a cause of death increased over this 10-years period (4.7% in 1995 vs 31.2% in 2005, p<0.01). Treatment of hepatitis C in patients who died from ESLD was more frequent in 2005 (37.5%) than in 1995 (19.0%), p<0.01.

 

Conclusions:

In HIV-HCV coinfected patients, the proportion of HCV-ESLD is still increasing and it constitutes a leading cause of mortality in this population.

 

Table 1.Characteristics of patients who died from ESLD in 1995, 1997, 2001, 2003 and 2005

 

1995

n = 21

1997

n = 36

2001

n = 38

2003

n = 27

2005

n = 64

Sex, male, no (%)

15 (71.4)

30 (83.3)

30 (78.9)

22 (81)

53 (83)

Mean age, y (range)

41 (26-66)

42 (31-62)

42 (32-69)

42 (36-54)

45 (35-68)

Injection drug use, no (%)

6 (28.5)

14 (38)

29 (76.3)

26/26 (100)

39/63 (61.9)

Alcohol consumption > 30g/day, no (%)

6 (28.5)

16 (44.4)

19 (50)

16 (59.2)

28/60 (46.6)

HBsAg positive, no (%)

8 (38.1)

15 (41.7)

8 (21.1)

2 (7.4)

17 (26.5)

HCC, no (%)

1 (4.7)

4 (11.1)

9 (25)

4 (14.8)

20 (31.2)

Anti-HCV treatment, no (%)

4 (19)

3 (8.3)

10 (26.3)

12 (44.4)

24 (37.5)

CD4 count (cells/mm3), median (IQR)

113 (27-257)

131 (46-306

158 (72-303)

132 (66-350)

239 (110-355)

HAART, no (%)

0

15 (41.6)

28 (73.6)

23 (85)

58 (90.6)

ESLD, end-stage liver disease; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; HAART, highly active antiretroviral therapy

 


Topic: HCV Epidemiology – Tattoos

136. Strong Association between Tattoos and Hepatitis C Virus Infection: A Multicenter Study of 3,871 Patients

S. Dhalla; C. T. Tenner; A. Aytaman; N. B. Shukla; G. Villanueva; G. Punla; C. Patterson; J. Comas; E. J. Bini 

 

Background:

Although injection drug use and blood transfusions prior to 1992 are well-accepted risk factors for hepatitis C virus (HCV) infection, the evidence for tattoos as a risk factor for HCV is conflicting. Furthermore, several prior studies that have evaluated tattoos as a risk factor for HCV infection were potentially confounded by injection drug use. The aim of this study was to determine the association between tattoos and HCV infection in a large population of patients without traditional risk factors for HCV infection.

 

Methods:

Patients with chronic HCV infection (HCV RNA positive) and controls (HCV antibody negative) completed a detailed questionnaire at the time of their scheduled visit to the outpatient primary care or GI clinic at 3 study sites. Data collected included patient demographics and information on HCV risk factors.

 

Results:

A total of 3,871 patients were enrolled, including 1,930 with chronic HCV infection and 1,941 HCV negative controls. There were no differences in the mean age (55.2 ± 9.0 vs. 55.6 ± 11.3 years, p = 0.34) or the proportion who were male (80.3% vs. 81.4%, p = 0.39) between HCV-infected patients and controls. However, HCV positive patients were more likely to be racial/ethnic minorities (78.5% vs. 56.5%, p <0.001). As expected, injection drug use (65.9% vs. 17.8%, p < 0.001) and blood transfusions prior to 1992 (22.3% vs. 11.1%, p <0.001) were more common in HCV-infected patients than in control subjects. Patients with HCV infection were significantly more likely to have had one or more tattoos (35.2% vs. 12.5%; OR = 3.81; 95% CI, 3.24 – 4.49; p <0.001) and this remained highly significant after adjustment for age, sex, and race/ethnicity (OR = 4.57; 95% CI, 3.83 – 5.45; p <0.001). After excluding all patients with a history of ever injecting drugs and those who have had a blood transfusion prior to 1992, a total of 1,887 subjects remained for analysis (466 HCV positive and 1,421 controls). Among these 1,887 patients without traditional risk factors for HCV infection, we found that HCV positive patients were still significantly more likely to have a history of tattoos (34.1% vs. 11.9%; OR = 3.84; 95% CI, 2.99 – 4.93; p <0.001) and this remained highly statistically significant after adjustment for age, sex, and race/ethnicity (OR = 4.47; 95% CI, 3.42 – 5.83; p <0.001).

 

Conclusions:

Tattoos are strongly associated with HCV infection, even among those without traditional HCV risk factors such as injection drug use and blood transfusions. All patients with tattoos should be offered HCV testing.

 


Topic: HCV Epidemiology – General

137. Evidence of international transmission of HCV in pan-European study of HIV-positive men who have sex with men (MSM).

M. Danta; T. van de Laar; D. Brown; O. Pybus; S. Bhagani; M. Vogel; S. Neifer; A. Baumgarten; H. Gotz; J. Rockstoh; S. Bruisten; G. M. Dusheiko 

 

Introduction:

Since 2000, there has been a reported rise in permucosal HCV transmission among European HIV-positive MSM related to high-risk sexual behaviours. We conducted a phylogenetic study to investigate the presence of a HCV transmission network among European MSM.

 

Methods:

HIV-positive MSM diagnosed with acute HCV (n=178) in England, Netherlands and Germany between January 2000 and December 2006 were enrolled into a molecular phylogenetic study. Part of the NS5B region of the HCV genome (436 bp) was amplified using RT-PCR and subsequently sequenced and genotyped. NS5B phylogentic trees were constructed using MEGA 3.1 software, comparing MSM cases with unrelated NS5B sequences.

 

Results:

NS5B sequences were obtained from 154/178 (87%) of cases; UK 86/107 (80%); Netherlands 46/47 (98%); Germany 22/24 (92%). Circulating HCV strains were of subtype 1a (60%), 4d (23%), 3a (8%), 1b (6%), 2b and 2c (3%). Phylogenetic analysis revealed 10 distinct HCV clusters (containing between 3-36 individuals; bootstrap values >70%) involving 129 (84%) of the sequences. Six of the ten clusters contained sequences from more than one country; 3 clusters contained sequences from all three countries. The majority (66%) of HCV sequences were in the five largest clusters, all of which contained sequences from different countries. There was a trend to country specific segregation occurring in smaller clusters compared with country non-specific clusters (4.5 median sequences/cluster versus 15.5 median sequences/cluster, p=0.07).

 

Conclusion:

This phylogenetic analysis reveals a large HCV transmission network among HIV-positive MSM in Europe. International mixing increases with cluster size, emphasising the rapid spread of regional outbreaks to neighbouring countries, presumably through increased travel associated with high-risk behaviours. The emergence of co-circulating HCV lineages supports transmission related to behavioural change among MSM rather than intrinsic viral change. This has important implications for public health agencies mitigating HCV transmission.

 


Topic: HCV Epidemiology – HIV/HCV Coinfection

138. HIV-HCV coinfection: similar rates of cirrhosis and death than HCV alone, outcomes not averted by HAART

A. Monto; S. Currie; L. M. Dove; D. Tracy; S. George; A. Myers; J. C. Ryan; T. L. Wright 

 

Background:

HIV coinfection may accelerate the complications of hepatitis C virus (HCV) infection. Much of this perception, however, has been based on retrospective case series or short-term prospective follow-up.

 

Aim:

To explore mortality and liver-related complications in a prospective cohort of American inner-city injection drug users, followed at an urban county and a veterans hospital, who have chronic HCV.

 

Methods:

350 patients were enrolled beginning in 1997 and have been followed for a mean of 4.8 years. 176 patients (49.7%)are chronically coinfected with HIV and hepatitis C, and 174 patients had chronic HCV infection alone. Causes of death were determined by the investigators, and were attributed to HIV, end-stage liver disease (ESLD) or drugs only when this was unequivocal. Cirrhosis was defined by histology or overt clinical or radiological evidence of cirrhosis.

 

Results:

Overall, 48 HIV-HCV coinfected and 34 HCV monoinfected patients died during follow-up, but coinfected patients did not have statistically-significantly increased death than the group overall (O.R. 1.54, 95% CI 0.94-2.54, p=0.09), data shown in Table. Similar proportions of coinfected patients were also found to develop cirrhosis, 29 (16%), as compared to monoinfected patients, 31 (18%, t-test p=NS). HAART was not protective against death in coinfected patients: 34/48 (71%) of coinfected patients who died had regularly received HAART, 29% had not (t-test p=NS).

 

Conclusions:

HIV-HCV coinfected and HCV monoinfected patients, when followed prospectively, have similar rates of death or cirrhosis. End-stage liver disease and HIV are competing causes of death in coinfected patients. Reported high rates of ESLD-associated death in coinfected patients alive today should be interpreted with caution, and compared to those in similar groups of HCV monoinfected patients. As the HAART era continues, morbidity and mortality in HIV-positive patients may approach that of their HIV-negative counterparts.

Table 1. Clinical Outcomes

HIV-HCV

Deaths

Overall

48 (27%)

 

 

HIV-Assoc

7 (4%)

 

 

Other

18 (10%)

 

 

ESLD-Assoc

12(7%)

 

 

Drug-related

0 (0%)

 

 

Unknown

11 (6%)

 

Cirrhosis

 

29 (16%)

HCV

Deaths

Overall

34 (19%)

 

 

Other

16 (9%)

 

 

ESLD-Assoc

6 (3%)

 

 

Drug-related

1 (1%)

 

 

Unknown

11 (6%)

 

Cirrhosis

 

31 (18%)

 


Topic: Treatment – Pegasys

LB1. Prolonged Antiviral Therapy With Peginterferon to Prevent Complications of Advanced Liver Disease Associated With Hepatitis C: Results of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial

A. M. Di Bisceglie; M. L. Shiffman; G. T. Everson; K. L. Lindsay; J. E. Everhart; E. C. Wright; W. M. Lee; A. S. Lok; H. Bonkovsky; T. R. Morgan; J. L. Dienstag; M. Ghany; C. Morishima; K. K. Snow 

 

Background:

Chronic hepatitis C may lead to progressive liver disease with cirrhosis, liver failure, hepatocellular carcinoma (HCC) and death. Not all pts treated with peginterferon and ribavirin achieve a sustained virologic response (SVR); whether long-term antiviral therapy can prevent progressive liver disease in those who do not achieve SVR remains uncertain.

 

Aims:

To determine if long-term maintenance therapy with peginterferon prevents progressive liver disease resulting from hepatitis C.

 

Methods:

We conducted a randomized controlled trial of peginterferon alfa-2a (90 mcg per week) for 3.5 years vs. no treatment in pts with chronic hepatitis C and advanced fibrosis who were nonresponders to prior therapy with peginterferon and ribavirin. Subjects eligible for enrollment had chronic hepatitis C with an Ishak fibrosis score of 3 on liver biopsy, a Child-Turcotte-Pugh (CTP) score of 6, no history of ascites, encephalopathy or bleeding varices, and no other identifiable cause of liver disease. Participants were stratified according to their stage of fibrosis – Ishak stage 3 or 4 (622 with fibrosis) vs. 5 or 6 (428 with cirrhosis). Pts were seen at 3 month intervals, underwent liver biopsy at 1.5 and 3.5 years after randomization, and were monitored for the following outcomes: death, HCC, hepatic decompensation (variceal hemorrhage, ascites, spontaneous bacterial peritonitis, encephalopathy or a CTP score of 7), and, for those with pre-cirrhotic fibrosis at baseline, an increase in fibrosis score of 2 points.

 

Results:

1050 pts were randomized (517 treatment, 533 control). By the end of the study, 34.1% of the treatment and 33.8% of the control group had experienced an outcome (hazard ratio=1.01; 95% CI=0.81-1.26; p=0.91). Although mean serum ALT and HCV RNA levels decreased significantly with treatment (both p<0.0001), as did necroinflammatory changes on liver biopsy (p<0.0001), no significant difference was observed in rates of any of the primary outcomes between groups (Table). The rate of serious adverse events was similar in both groups (284 events among 175 treated and 283 events among 155 control pts). Among treated pts, 17% stopped peginterferon by year 1.5 and 30% by year 3.5.

 

Summary and Conclusions:

Long-term therapy with peginterferon did not reduce the rate of disease progression. These findings do not support maintenance therapy with peginterferon in patients with chronic hepatitis C and advanced hepatic fibrosis who are nonresponders to a course of peginterferon/ribavirin therapy.

 

Death (%)

Decompensation (%)

HCC (%)

Increase in fibrosis (%)

Treatment (n=517)

 

6.6

 

14.3

 

2.8

 

28.2

Control (n=533)

4.6

13.2

3.2

31.9

 


Topic: HIV/HCV Coinfection

LB3. HIV entry and replication in stellate cells promotes cellular activation and fibrogenesis: Implications for hepatic fibrosis in HIV/HCV co-infection

A. C. Tuyama; F. Hong; A. D. Schecter; A. Mosoian; B. K. Chen; P. Chen; M. E. Klotman; M. B. Bansal 

 

Introduction:

Patients co-infected with HIV/HCV develop more rapid fibrosis than patients mono-infected with HCV. Fibrosis progression correlates with HIV viremia suggesting a direct role of HIV in liver fibrogenesis. CCR5 and CXCR4 are the 2 major co-receptors required for HIV entry into cells. CCR5 has been reported on hepatic stellate cells (HSCs) and we have recently demonstrated the expression of CXCR4 on HSCs (Hong,#1400; AASLD 2007). Gp120 is the envelope protein for HIV and can activate cells independent of direct infection.

 

Aim:

The aim(s) of this study are to 1) Examine whether HIV enters HSCs and actively replicates 2) Characterize the impact of HIV and gp120 on HSC biology. First the capacity of HIV IIIB (CXCR4-tropic or X4) and HIV-Bal (CCR5-tropic or R5) to infect HSCs was assessed by ELISA for supernatant p24, a marker for virus being released from the cells. LX2 cells, a human HSC line, were infected and washed to remove unbound virus. Significant concentrations of p24 (>2ng/ml) were detected on all days examined (up to 7 days). Since X4 viruses predominate later in the course of HIV disease coincident with chronic liver disease in patients with HCV/HIV, we examined whether HIV IIIB infects primary human HSCs (passage #3-4) and replicates using p24 assay and qRT-PCR for unspliced(US) and multiply-spliced(MS) HIV-1 RNA. The detection of p24 (>8ng/ml)associated with intracellular US and MS HIV suggests active replication (confirmed by sequencing of MS HIV-1). The ability of HIV to infect HSCs was confirmed by challenging the cells with a recombinant HIV expressing GFP in place of the early gene nef. The finding of GFP-positive cells indicates HIV entry and early gene expression. As HIV infection may be either CD4-dependent or -independent, CD4 expression by HSCs was documented by immunofluorescence. CD4-blocking experiments revealed that HIV IIIB entry into HSCs was CD4-independent. HIV infection promoted HSC activation, since qRT-PCR demonstrated a 1.6-fold (p<0.0001) and 1.5-fold (p<0.0001) increase in collagen α1(I) and α-SMA mRNA levels, respectively. Furthermore, incubation with either monomeric gp120(X4) or AT-2 treated X4(oligomeric gp120) for 1-24 hrs resulted in a 2.1-fold (p<0.007) and 1.4-fold (P<0.004) increase in collagen α1(I) mRNA levels, respectively.

 

Conclusions:

HIV enters and actively replicates within HSCs independent of CD4. Both viral entry as well as exposure of cells to viral envelope glycoproteins can promote activation and collagen induction in HSCs. These results suggest that direct infection or Env-mediated activation of HSCs may contribute to rapid development of fibrosis in patients co-infected with HIV/HCV.

 


Topic: Treatment – Pegasys

LB4. Pegylated interferon alfa-2a (40KD) plus ribavirin (RBV) in prior non-responders to pegylated interferon alfa-2b (12KD)/RBV: final efficacy and safety outcomes of the REPEAT study

D. M. Jensen; B. Freilich; P. Andreone; A. DiBisceglie; C. E. Brandão-Mello; K. Reddy; A. Craxi; A. Martín; G. Teuber; D. Messinger; G. Hooper; M. Popescu; P. Marcellin 

 

Introduction:

Treatment options are limited for patients (pts) who are previous non-responders to Peg-IFN/RBV. Intensified treatment with higher fixed-dose induction of Peg-IFN and/or longer treatment duration may increase SVR rates in these pts. REPEAT compared both strategies in prior non-responders to ≥12 wks of Peg-IFN α-2b (12KD, PegIntron®)/RBV.

 

Methods:

Eligible pts were randomized (2:1:1:2) to 1 of 4 regimens, Arms A and B Peg-IFN α-2a (40KD; PEGASYS®) 360 μg/wk for 12 wks then 180 μg/wk for a further 60 or 36 wks, respectively; Arms C and D Peg-IFN α-2a (40KD) 180 μg/wk for 72 or 48 wks, respectively. All pts received RBV (COPEGUS®; 1000/1200 mg/day). The primary endpoint was SVR (HCV RNA <50 IU/mL 24 weeks post-therapy).

 

Results:

A total of 942 pts were randomized and dosed. Key baseline (BL) characteristics were similar across arms. For the protocol-defined primary analysis the SVR rate was higher for the 72-wk induction arm (Arm A: 16%) compared to the 48-wk non-induction arm (Arm D: 9%) [p=0.006, OR 2.0 (95% CI 1.21-3.31)]. Furthermore, SVR was higher for pooled 72-wk arms vs pooled 48-wk arms [p=0.0006, OR 2.22 (95% CI 1.40-3.52)]. Tolerability of induction and non-induction regimens of Peg-IFN α-2a were similar and overall the rate/type of AEs/SAEs were similar across arms. Discontinuation rates due to safety were lower for the 48-wks arms.

 

Conclusion:

In these difficult to cure pts with prior documented non-response to Peg-IFN α-2b/RBV, re-treatment with fixed-dose induction and longer duration with Peg-IFN α-2a (40KD)/RBV provided the highest SVR rates and the lowest relapse rates. Re-treatment with 72-wks of Peg-IFN α-2a provided higher SVR rates than 48-wks, irrespective of induction.

 

 

Peg-IFN α-2a (40KD) plus RBV 1000/1200 mg/day

 

A (n=317)

360/180 μg/wk

(72 wk)

B (n=156)

360/180 μg/wk

(48 wk)

C (n=156)

180 μg/wk

(72 wk)

D (n=313)

180 μg/wk

(48 wk)

Males (%)

64%

60%

69%

68%

Mean ± SD Age (yrs)

48.1 ± 8.7

48.8 ± 9.9

49.4 ± 8.5

48.5 ± 9.0

Caucasian (%)

88%

90%

88%

90%

Mean ± SD Weight (kg)

81.5 ± 18.2

81.1 ± 16.8

81.2 ± 16.0

80.9 ± 16.9

Genotype 1 (%)

91%

91%

91%

91%

Mean ± SD BL HCV RNA (x 106 IU/mL)

 

5.4 ± 6.4

 

5.3 ± 7.1

 

4.9 ± 5.1

 

4.9 ± 6.0

Cirrhosis (%)

25%

29%

30%

28%

EoT response rate, n (%)

99 (31%)

52 (33%)

48 (31%)

88 (28%)

SVR rate, n/N (%)

Overall

 

BL VL ≤800 000

 

BL VL >800 000

 

52/317 (16%)

 

22/61 (36%)

 

29/244 (12%)

 

11/156 (7%)

 

2/22 (9%)

 

9/130 (7%)

 

22/156 (14%)

 

5/25 (20%)

 

17/128 (13%)

 

27/313 (9%)

 

9/62 (15%)

 

16/233 (7%)

Relapse Rate, n/N* (%)

48/92 (52%)

38/49 (78%)

30/47 (64%)

55/81 (68%)

Premature d/c for safety, n (%)

 

37 (12%)

 

7 (4%)

 

18 (12%)

 

20 (6%)

Pts with SAEs, n (%)

Overall

Hematological

 

33 (10%)

5 (2%)

 

14 (9%)

-

 

28 (18%)

3 (2%)

 

33 (11%)

6 (2%)

Peg-IFN α-2a dose modifications, n (%)

 

72 (23%)

 

41 (26%)

 

36 (23%)

 

57 (18%)

*N=Pts with negative EoT HCV RNA and ≥1 post-EoT HCV RNA value

 


Topic: Experimental Treatment – VX-950

80. PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis

C. Hezode; P. Ferenci; G. M. Dusheiko; S. Pol; T. Goeser; J. Bronowicki; S. Gharakhanian; D. Devonish; R. Kauffman; J. Alam; J. Pawlotsky; S. Zeuzem 

 

Background:

PROVE2, study VX05-950-104EU is a randomized, placebo-controlled phase II study of telaprevir (TVR), in combination with pegylated interferon alfa2a (Peg-IFN) and ribavirin (RBV), in treatment naïve subjects with genotype 1 chronic hepatitis C infection. Results of a planned interim, on-treatment, safety and efficacy analysis (IA) are reported.

 

Methods:

A total of 332 subjects were randomized into four groups.

·        Group A received standard of care Peg-IFN 180 mcg/weekly + RBV 1000-1200 mg, weight-based and TVR-placebo for 48 weeks.

·        Group B TVR 750 mg q8h together with Peg-IFN+RBV for 12 weeks, followed by Peg-IFN and RBV for a further 12 weeks.

·        Group C, TVR 750 q8h with Peg-IFN + RBV for 12 weeks.

·        Group D, TVR + Peg-IFN for 12 wks. The Roche Taqman assay was used to quantify plasma HCV RNA (LOD 10 IU/mL).

This first IA was performed when at least 90% of subjects completed the week 12 visit.

 

Results:

The median age was 45 years (18-65), median weight 70.9 kg (45-115), 58.7% were male, 94.1% Caucasian, 7.5 % had stage F3 fibrosis, 34.1% were infected with genotype 1a, and 54.1% with 1b. The median baseline HCV RNA was 6.4 Log10IU/ml (3.3-7.7). Overall, discontinuation occurred in 6.4% of Group A, 17.1% of Groups B+C and 10.5% of Group D subjects prior to week 12. Discontinuations for AEs, occurred in 2.6% of Group A, 12.5% of Groups B+C and 7.9% of Group D subjects. Pruritis, rash, asthenia, nausea, and anemia were the most common AEs associated with TVR; anemia and nausea were less frequent in Group D. The table summarizes ITT viral responses.

 

Conclusion:

TVR (Telaprevir, VX950)+Peg-IFN+RBV produces a significantly greater, on-treatment, anti-viral response at weeks 4 and 12 compared to Peg-IFN+RBV in naïve subjects with genotype 1 HCV. Dosing without RBV reduced the on-treatment anti-viral response; further follow-up will evaluate effects on SVR and relapse rates. Consistent with prior studies, the adverse event profile showed that skin events, nausea and anemia are the most important AE’s associated with TVR. Further results will confirm the optimal treatment duration and dosage regimen for Phase 3.

 

HCV RNA Un-detectable

Group A (%)

(n=77)

Groups B+C (%)

 

(n=152)

Group D (%)

 

(n=76)

Week 4

14.3

74.3*

52.6*

Week 12

42.9

78.9*

63.2+

*p<0.001 compared to Group A; +p=0.015 compared to group A


Topic: Experimental Treatment – General

84. A pilot randomized controlled study evaluating efficacy of autologous bone marrow mononuclear cells transplantation in patients with advanced chronic liver disease.

A. C. Lyra; M. B. Soares; L. F. da Silva; E. L. Braga; S. A. Oliveira; M. F. Fortes; A. G. Silva; P. S. Brandão ; B. Genser; R. R. dos Santos; L. G. Lyra 

 

Introduction:

Studies in animal models of liver disease have shown that bone marrow cells (BMC) transplantation improves hepatic fibrosis and liver function. Other authors and we have recently demonstrated that autologous BMC therapy in patients with chronic liver disease is safe and feasible and may induce changes in liver function tests.

 

Aim:

To evaluate the efficacy of BMC transplantation in patients with advanced chronic liver disease.

 

Methods:

Thirty patients on the waiting list for liver transplantation were randomly assigned to receive BMC therapy or no treatment in a nonblinded fashion. Approximately 50 ml of bone marrow aspirate were prepared by centrifugation in a ficoll-hypaque gradient. A minimum of 100 millions autologous mononuclear-enriched BMC were infused into the hepatic artery. Baseline assessment included clinical, laboratorial and abdominal MRI evaluation. Serum albumin, bilirubin, INR, Child-Pugh and MELD score were chosen as endpoints to assess efficacy. Patients were closely assessed for clinical events and changes in liver function for 90 days. Statistical analysis was conducted by obtaining descriptive statistics, calculating mean changes from baseline and fitting a random effects model to compare the profiles of liver tests of both groups.

 

Results:

Mean age, baseline liver function tests (except for albumin), MELD and Child-Pugh score were similar in both groups. Albumin levels (g/dl) were higher in the control group (3.31 vs 2.79, p=0.053). During follow-up one patient died and one was liver transplanted in the control group while another patient died in the intervention group. No other major complications were detected in the remaining patients. Albumin levels increased in the treatment arm while they remained stable among controls up to 90 days (P=0.034; BMC group relative change from baseline (RC) = +16%, control group RC = +2%). Child Pugh score significantly decreased in the therapy group compared to the control group (P=0.017, BMC group RC = -8%, controls RC = +4%). Bilirubin levels significantly increased among controls while they decreased in the treatment arm during the first 60 days after therapy and increased to baseline levels after 90 days. INR profile was not significantly different between both groups.

 

Conclusions:

Transplantation of autologous BMC into the hepatic artery appears to improve liver function of patients with advanced chronic liver disease at least for up to 90 days and might be a promising treatment option for these subjects. Larger studies with longer follow-up are necessary to validate our findings, to define the duration of this beneficial effect and to determine if there will be improvement of survival.


Topic: Epidemiology

 

872. A New Genotype of Hepatitis C Virus Originating from Central Africa

D. Murphy; J. Chamberland; R. Dandavino; E. Sablon

 

The characterization of hepatitis C virus (HCV) variants from different parts of the world has shown that they can be classified into 6 genotypes. Their distributions differ geographically. Genotypes 1, 2 and 4 display significant genetic diversity in Africa while genotypes 3 and 6 show high genetic diversity in southern Asia. On the other hand, genotype 5 is comprised of only one subtype and its origin remains to be established. We have identified three variants (QC69, CS101285 and CS101300) that cluster together but do not classify within the 6 genotypes of HCV.

 

Methods:

In order to better characterize these variants and to study their evolutionary relationships with the other genotypes, the entire coding region sequence of QC69 and partial coding region sequences of CS101285 and CS101300 were determined. QC69 was isolated from a patient residing in Canada while CS101285 and CS101300 were obtained from patients residing in Belgium. However, all three patients originated from the Democratic Republic of Congo where they are believed to have been infected. QC69 contained an open reading frame of 3013 amino acids. It showed 33.4% to 35.5% nucleotide and 28.1% to 31.0% amino acid divergence with genotypes 1a-H77, 2a-HCJ6, 3a-NZL1, 4a-ED43, 5a-EUH1480 and 6a-EUHK2. Phylogenetic analysis based on complete coding region sequences (Figure) shows that QC69 forms a branch distinct from other genotypes confirming that it constitutes a novel HCV genotype. Additional analysis performed on individual gene regions indicates a closer relationship between QC69 and genotype 2 variants analogous to the relationship observed between genotype 1 and 4 variants.

 

Results:

This analysis also showed that QC69 was not produced as a result of recombination events between known genotypes. Further epidemiological studies based on coding region sequences are required to determine the prevalence and spread of this genotype in Africa.

 

Conclusions:

The finding of a new genotype in Central Africa will contribute in elucidating the origin of the worldwide HCV epidemic. We propose that these three isolates be classified as genotype 7 of HCV.

 

 


Topic: Epidemiology

 

873. Outbreak of a new hepatitis C virus subtype (subtype 1m) in a hemodialysis unit

S. Chevaliez; R. Brillet; J. Sehonou; L. Barbotte; J. Pawlotsky

 

Introduction:

Nosocomial transmission, especially in the hemodialysis setting, currently is one of the most frequent causes of hepatitis C virus (HCV) infection worldwide. We describe an outbreak of a new HCV genotype 1 subtype in a hemodialysis unit, illustrating how new HCV genotypes may spread in the developing world and further.

 

Methods:

The 64 patients undergoing regular renal dialysis in the hemodialysis unit of Hubert Kutuku Maga hospital in Cotonou, Benin (Africa) have been tested for the presence of anti-HCV antibodies and HCV RNA. Two HCV genomic regions, located within the non-structural 5B and the core-E1 coding regions, have been PCR-amplified and sequenced in all cases at the French National Reference Center for Viral Hepatitis B, C and delta. Genetic and phylogenetic analyses have been performed to assess the genetic relatedness between the strains, in order to evaluate the frequency of between-patient transmissions in the context of hemodialysis.

 

Results:

19 hemodialysis patients out of 64 (29.7%) were HCV-infected; 17 of them were infected with HCV genotype 1, one with genotype 2 and one with genotype 3. Among the 17 patients infected with genotype 1, 4 (23.5%) were infected with subtype 1i, one (5.9%) with subtype 1b, and 12 (70.6%) could not be subtyped. The 4 patients infected with genotype 1i clustered together and distinctively from other reference genotype 1i strains, suggesting between-patient transmissions in the hemodialysis unit. In the 12 patients that could not be subtyped, the sequences were analyzed by a variety of distance-based, parsimony, and maximum-likelihood methods and evidence was sought for consistent phylogenetic grouping together and distinctness from other subtypes. All studied HCV strains were closely related together and segregated into one monophyletic cluster with high bootstrapping values, suggesting nosocomial transmission in the hemodialysis unit. Furthermore, these strains differed from all of the known HCV genotype 1 subtype nucleotide sequences (1a to 1l) by 16-26% in the NS5B region and 24-33% in the core-E1 region. Since the cluster members diverged from subtypes 1a to 1l by more than 15% of their nucleotide sequence, they could be assigned a new, provisional subtype designation: subtype 1m.

 

Conclusion:

We report a high prevalence of nosocomial transmission of HCV in a hemodialysis unit in Benin, Africa. We identified a new subtype of HCV genotype 1, provisionally designated as subtype 1m, that was heavily transmitted among the regular hemodialysis patients. This study witnesses how new subtypes of HCV genotypes may be transmitted though nosocomial routes in the developing world before further spreading.

 


Topic: Epidemiology

 

875. Hepatitis C testing, care and treatment: evolution over ten years in France

C. Meffre; E. Delarocque-Astagneau; C. Pioche; F. Dubois; F. Roudot-Thoraval; D. Guyader; C. Silvain; Y. Le Strat; J. Desenclos

 

Introduction:

With a prevalence of Hepatitis C virus antibodies (anti-HCV) of about 1% in the population in 1994, hepatitis C was considered as a serious public health issue by French health authorities that consequently implemented a national prevention and control program in 1999. To assess its impact we set up two surveillance systems to 1) monitor trends in anti-HCV screening (Rena-VHC) and 2) to follow up epidemiological-clinical characteristics of HCV patients newly referred for care and treatment in hepatology centres (Pôles-de-Référence) and conducted a population based prevalence survey in 2004. We present the change over time of several key indicators.

 

Methods:

We used four data sources. Two were national cross sectional population-based serosurveys of French adult metropolitan residents that collected risk factors and awareness of HCV infection. Serum samples were tested for anti-HCV and HCV RNA. The third was Rena-VHC, based on 159 laboratories spread all over France that report number of performed anti-HCV tests, number of positive tests, age and sex of positive diagnosed persons. The forth was Pôles-de-Référence which relies on 26 hepatitis C reference centres and describes clinical and epidemiological characteristics of newly referred patients, including circumstances of anti-HCV testing, risk exposure for HCV transmission, HCV RNA serum status and severe liver disease (cirrhosis,hepatocarcinoma).

 

Results:

Prevalence results from 1994 and 2004 Serosurveys, France

Study Population

1994

2004

 

 

20-59 year-old

 

20-59 year-old

 

18-80 year-old

Anti-HCV prevalence (%)

1.5

(CI95%:0.75-1.34)

0.71

(CI95%:0.52-0.97)

0.84

(CI95%:0.65-1.10)

% of HCV RNA + among anti-HCV+

 

 

81

 

57

(CI95%:40-72)

 

 

65

(CI95%:50-78

 

The proportion of those who were aware of the HCV status:

·        1994, overall                             24%

·        2004, overall                             56%

·        2004 (IDU)                               93%

·        2004 (Transfusion < 1992)        72%

·        2004 Others                              28%

 

Treatment:

From 2001 to 2005:

·        Past excessive alcohol intake remains high (38% in mailes, 11% in females) in patients newly referred for treatment particularly in those reporting drug use (50% in males, 30% in females).

·        Proportion of genotyped patients increased from 55% in 2001 to 83% in 2005.

 

Conclusion:

 

From 1994 to 2004:

 

·        Anti-HCV prevalence decreased in the general population, which may indicate some impact of the hepatitis C programme.

·        Proportion of HCV RNA positive persons deceased, which may be due to improvement of treatment and therapeutic efficacy.

·        Awareness of anti-HCV positive status increased which suggests an increase of HCV screening.

 

From 2004 to 2005:

 

·        Increase of testing from 2000 and decrease of proportion of positive diagnosed persons from 2003, suggest that rec engtly more persons at lower risk have been screened.

·        Alcohol consumption in patients who reported drug use underlines the need of an integrated treatment of HCV and alcohol dependence.

·        Remaining high proportion of patients with severe complications (cirrhosis, HCC) when newly treated, indicates that earlier screening is still warranted for an at risk patients.

 


Topic: Epidemiology

 

874 Hepatitis C virus RNA is Detected in Cervicovaginal Fluids of Menstruating Women, in a Menopausal Woman with Bloody Cervicovaginal fluid, but not in Women who have had Hysterectomy.

C. C. Wang; L. Cook; S. Holte; M. Krows; A. Bagabag; K. Ng; K. Jerome, ; L. Corey

 

Objective:  

Sexual transmission of hepatitis C (HCV) accounts for approximately 20% of new infections. Nevertheless, the presence of HCV RNA in the female genital tract has not been extensively examined; in 3 published cross-sectional studies, 19-25% of women of childbearing age had detectable HCV RNA. We sought to define the prevalence of female genital tract HCV RNA shedding in a prospective study of pre- and post-menopausal women.

 

Methods:

Women with untreated chronic HCV and detectable serum HCV RNA were enrolled. Menstrual status and history of hysterectomy were recorded. Women inserted two Dacron swab into their vaginas every morning as they would a tampon, placed the swabs into dry cryovials, and stored them immediately in their home freezers for 18-56 consecutive days. Menstruating women indicated menstruation dates. HCV RNA and hemoglobin were detected in cervicovaginal fluids using real-time RT PCR and spectrophotometry, respectively. Statistical analyses were performed using nonparametric tests and generalized estimating equations taking into account repeated measures.

 

Results:

16 women were enrolled; median age was 50 (range 27-59). Seven women were menstruating, 6 were menopausal, and 3 had had hysterectomies. Baseline serum VL was 6.43 (range 5.17-7.36 log10 IU/ml) and did not differ by menstruation or hysterectomy status. Menstruating women were more likely than menopausal women to have HCV RNA detected in cervicovaginal fluids on at least one day (86% versus 16%, p=.02). For menstruating women, detection of HCV RNA was more likely during menstruation (OR= 56.4, 95% CI (23.0,138.3)) or when hemoglobin was detected in cervicovaginal fluids, even when menstruation was not occurring (OR= 35.4 , 95% CI (12.2,102.6)). The median quantity of HCV RNA detected in cervicovaginal fluids in menstruating women was 4,631 (range 231-69,580 IU/ml). Only 1 menopausal woman had HCV RNA detected in cervicovaginal fluids; she also had hemoglobin detected on 8 days during the 56 day sample collection period.

 

Conclusion:

In women with chronic hepatitis C, HCV RNA detection in cervicovaginal fluids is associated with menstruation or the detection of hemoglobin on non-menstruation days. HCV RNA was not detected in women who had had hysterectomies, suggesting that the presence of the cervix plays a role in HCV RNA genital tract shedding in women. The quantity of HCV RNA detected was low, supporting the epidemiologic finding that HCV is not efficiently transmitted sexually. These findings highlight the fact that HCV is primarily a blood-borne virus, and may have implications for menstruating women with chronic hepatitis C.

 


Topic: Epidemiology

 

876. Injection drug use, social networks and hepatitis C: understanding the behavioural and immunovirological factors leading to transmission - The Networks II Study

M. E. Hellard; C. Aitken; M. Bharadwaj; S. D. Bowden

 

Introduction:

Hepatitis C virus (HCV) infection affects an estimated 180 million people worldwide, and causes 50–76% of liver cancers and two thirds of liver transplants in the developed world. The burden of disease and costs attributable to HCV-related chronic liver disease will grow due to complications of cirrhosis and hepatocellular carcinoma in ageing chronically-infected cohorts and as new HCV infections arise. It is imperative that research efforts focus on ways to prevent new HCV infections to reduce the global burden of disease.

 

Methods:

In Networks II study we established a longitudinal IDU cohort study; 251 IDUs are followed for two years. Networks II enables us to study HCV transmission (naive recurrent and and superinfection) and behavioural and immunological determinants of this and HCV clearance using a social network approach where the relationship between the IDUs is studied.

 

Results:

Recruitment commenced in Melbourne, Australia in July 2005. Every three months participants completed a questionnaire about sexual, injecting and other risk behaviour, network data, and provided a blood samples. Blood tests included HCV antibody, HCV RNA, genotype and molecular sequencing. Samples were also HLA typed and then tested for HCV specific CD8+ T cell response using minimal T cell epitopes. We describe the results for the first year of the study.

 

The traditional (naïve) incidence in our cohort to date is 29.1% per annum (95% CI 17.5, 48.3) and 79.2% (95% CI 25.5, 245.4) in IDUs injecting for less than one year. The incidence of reinfection was 50.6% pa (33.3, 76.9) and of superinfection 20.8% pa (12.9, 33.4).

 

A key driver of HCV infection was having all members of your network HCV- infected whereas the number of injecting partners and the level of needle-sharing were less important when measuring disease transmission.

 

We identified 39 persistently HCV RNA negative people who injected with >=1 RNA-positive partner, and six who recently injected with a needle used by >=1 RNA-positive partner; this suggests they possess innate resistance or develop protective immunity. Our immunological data suggest that IDUs who clear HCV maintain functionally potent memory CD8+T cells that are highly cytotoxic and produce antiviral cytokines (IFNg and TNFa); conversely, CD8+T cells from IDUs with persistent HCV infection are functionally downregulated with compromised cytotoxic and cytokine secreting capacity.

 

Conclusion:

The results of Networks II thus far have advance understanding of the dynamics and immunovirology of HCV infection transmission. It is our expectation that the study will provide further insights that will contribute to HCV prevention intervention strategies and vaccine development.

 


Topic: Epidemiology

 

877. Barriers to Healthcare Access Among Chronic Hepatitis C Patients

D. Evon; A. Verma; K. Simpson; S. Smith; M. W. Fried

 

Purpose:

People with chronic hepatitis C (HCV) may face barriers to accessing health services. The aims of this study were to determine the extent to which perceived barriers may complicate HCV care and to examine the relationship between barriers and socioeconomic (SES) factors.

 

Methods:

One hundred and twenty eight (n=128) patients referred for HCV at two hepatology centers completed instruments on a laptop computer during one of their first two clinic visits. The Barriers to Care Scale (BACS), a 12-item scale with 4 subscales developed for HIV patients, was modified for this study. Items were rated on a 4-point scale, ranging from 1 (No problem) to 4 (Major Problem) to indicate the extent to which each barrier made it difficult to access HCV care. Nonparametric tests were used to explore associations between SES and BACS subscales.

 

Results:

The majority of participants were male (55%), Caucasian (81%), married (53%) with a mean age of 46 years. SES characteristics were as follows: Working full or part-time (70%); Household income of < 40K (56%); No insurance (11%); Traveled over 30 minutes to clinic (54%); and Lack of self-transportation (21%). The greatest barriers rated by participants were lack of personal financial resources, lack of HCV knowledge in their community, and feeling stigmatized for having HCV. Long distance to a hepatitis facility and lack of professionals competent in HCV care were also highly rated as barriers to HCV care (See Table 1). The following associations were found between BACS subscales and SES factors: 1) Distance was a barrier for unemployed patients(p=.04) and patients without self-transportation (p=.006); 2) Community stigma was greater for women compared to men (p=.04); and 3) Personal resources were a barrier for unmarried patients (p=.001), patients making < 40K (.000), unemployed patients (p=.001), patients without private insurance (p=.007), and patients without self-transportation (p=.000).

 

Conclusions:

HCV patients perceive numerous barriers to accessing HCV care, which are related in part to SES factors. These data must be considered when designing interventions to increase access to care for HCV patients.

 

Table 1: Barriers to Care (1= No problem; 4=Major problem)

Means(SD)

1. Geographical/Distance

- Long distance to facility

- Lack of transportation

 

1.9 (.90)

1.4 (.78)

2. Medical/Psychological

- Medical professionals who do not provide care for HCV

- Lack of professionals who are trained and competent in HCV

-Lack of mental health professionals

-Lack of psych/support groups for HCV

 

1.6 (.99)

1.9 (.99)

1.4 (.73)

1.6 (.83)

3. Community Stigma

- Level of knowledge about HCV in community

- Community stigma against persons with HCV

 

2.3 (1.08)

2.1 (.99)

4. Personal Resources

- Lack of employment opportunities for people with HCV

- Lack of understanding work environment for people with HCV

- Personal financial resources

- Lack of adequate and affordable housing

 

1.8 (1.07)

1.8 (1.03)

2.4 (1.10)

1.7 (.94)

 


Topic: Epidemiology

 

886. Correlates of incident HCV infection and seronegative-immune status in high risk, IDU prisoners

P. S. Haber; B. Cameron; L. Elliott; S. Teutsch; R. Ffrench.

 

Introduction:

High rates of hepatitis C (HCV) infection are reported amongst prison inmates, primarily linked to injecting drug use (IDU). HCV-specific cellular immunity is found in a small subset of high risk, seronegative subjects and may protect against chronic infection. Both factors are likely to influence incident infection rates and outcomes. The aim of this study is to determine HCV incidence in seronegative IDU prison inmates, the prevalence of HCV-specific immunity, and associated risk behaviours.

 

Subjects and methods:

Adult inmates have been recruited into a prospective cohort – the Hepatitis C Incidence and Transmission Study-II (HITS-II) study provided they are: greater than 17 years of age; have a lifetime history of IDU; and imprisonment and documented negative HCV antibody status within 12 months. Subjects complete a detailed interview to record demographics and risk behaviours. Blood is collected to screen for: HCV antibodies by ELISA (Innogenetics); HCV viraemia (Bayer); interferon-gamma production by enzyme-linked immunospot (ELISpot) and multiplex in vitro cytokine production following stimulation with HCV peptides. Thresholds for positive responses were based on data in low risk, seronegative subjects (n=15). The frequencies of demographic and behavioural risk factors were compared (SPSS for Windows v.13.0)

 

Results:

242 inmates have been enrolled, and 184 tested for HCV antibodies and viraemia. Five had antibody indeterminate status and were therefore excluded from the analyses. Of the 179 subjects, 39 (22%) had seroconverted. Female gender (p=0.047), an increased number of incarcerations (p=0.013), tattooing (p=0.021), and methadone treatment (p<0.0001) were associated with seroconversion.

 

Of the 179 subjects, 102 have been tested for HCV-specific immunity, with 22/78 seronegatives (28%) and 18/24 (75%) seroconverters having positive responses in the interferon gamma ELISpot. Seronegative-immune status was positively associated with specific patterns of IDU, and negatively with a recent break from IDU (all p<0.01). The specificity of the ELISpot responses differed in that anti-Core, NS2 and NS4a responses were not found in seronegative-immune subjects. The multiplex assay revealed that seronegative-immune subjects also had generally low levels of interleukin-10 and high levels of tumour necrosis factor-alpha production in response to NS4-5 stimulation.

 

Conclusions:

Both incident infection and seronegative-immune status are common in high risk IDU prisoners. Further follow-up of the subjects in the HITS cohort will evaluate the details of the predictive risk behaviours and protective efficacy of the immune responses.

 


Topic: Epidemiology

 

889  Community Trends in Diagnosis and Treatment of Hepatitis C

B. P. Yawn1; L. Rocca1; P. Wollan

 

Introduction:

National data shows decreasing rates of hepatitis C but little is known about community based rates of recognition and treatment.

 

Methods:

The Olmsted County, MN hepatitis C registry collects data on all people diagnosed with hepatitis C residing within the county. The registry is populated with demographic data, dates of diagnosis, risk factors, contraindications to treatment and treatment information. We present data on trends for rates of diagnosis, rates of treatment and treatment contra-indications from our registry.

 

Results:

The registry includes data on 626 people. The mean age at diagnosis is 43 years, and gender distribution is 373 men, 253 women and 26% received hepatitis C treatment.  Overall, 123 (2%) had mental health diagnoses.  The incident rate increased in 1995 to 15.5/10,000 person years (177cases); 2000 to 27.0/10,000 person years (337 cases); 2005 to 27.9/10,000 person years (375 cases).

 

Rates of treatment of newly identified cases have risen especially since 2000 (p for trend 0.001). (See Figure) At all times men were more likely than women to be treated.(p = 0.01) Although newly diagnosed cases are more likely to be treated, high percentages of previously diagnosed cases remain untreated due to chronic depression, chronic and relapsing alcohol and drug addiction. Very few patients were ever reassessed for treatment following identification of a contraindication.

 

Conclusion:

·        Hepatitis C remains common.

·        In the community, treatment rates have increased  but a large percentage of those with hepatitis C remain untreated.

An increasing prevalence of alcohol dependence and biopolar disorder are present in those with hepatitis C who are untreated. 

 


Topic: Epidemiology

 

890.  Does gender matter? A prospective evaluation of risk factors for HCV infection and treatment candidacy in women

S. Currie; H. Shen; N. Brau; B. S. Anand; A. Aytaman; K. Chang; R. Cheung; T. R. Morgan; M. Pedrosa; W. N. Schmidt; A. Monto1; R. McQuaid; T. L. Wright; E. J. Bini

 

Background:

Historically, women have comprised a small percentage of the veteran population. However, they are now the fastest growing group of veterans. Because veterans have a higher overall prevalence of HCV than non-veterans, a better understanding of gender issues and HCV treatment candidacy may be especially important. Aim: To compare risk factors for HCV infection and treatment candidacy between women and men veterans.

 

Methods:

Data were prospectively collected in HCV RNA positive veterans from 24 Veterans Affairs Medical Centers. Risk factors for HCV were assessed by questionnaire and treatment candidacy was determined by standardized criteria. Patients were excluded from treatment if at least one of thirteen standardized criteria were met.

 

Results:

Of 4,269 patients, 118 (2.8%) were women. Univariate analyses showed that women were younger, more educated, and less likely to have a history of injection drug use, incarceration, heavy alcohol use or snorting cocaine, but were more likely to have had surgery, a needle stick injury or a blood transfusion. Despite these differences, baseline laboratory results and treatment candidacy (43% vs 40%, p = ns) were similar in men and women. Reasons for exclusion from therapy were similar in men vs women, such as ongoing substance use (20% vs 13%, p = 0.05), mental health issues (18% vs 19%, p = ns) and advanced liver disease (14% vs 13%, p = ns), but, as table one shows, men were more likely to have multiple contraindications to therapy (p<0.05). Men were also almost twice as likely as women to have 3 or more reasons for exclusion from therapy (OR=1.69, 95% CI=1.07 - 4.26).

 

Conclusions:

Women veterans with HCV have fewer high risk behaviors than men, yet their overall treatment candidacy rates are similar. These seemingly contradictory results may be due to patients’ exclusion from therapy based on only on a single contraindication and that women were much more likely than men to have only one reason for exclusion. These results suggest the need for gender-specific HCV risk factor screening and counseling, as well as an opportunity to improve treatment candidacy through substance use and mental health interventions, especially in women veterans who have fewer contraindications to HCV treatment.

 

Table 1. Exclusion criteria met for HCV treatment based on gender (maximum of 13 yes responses) N = 2,450

Exclusion Criteria

Women (n=64)

Men (n=2,386)

One exclusion criteria met

51 (79.6%)

1,665 (69.7%)

Two exclusion criteria met

12 (18.8%)

517 (21.7%)

Three or more exclusion criteria met

1 (1.6%)

204

(8.6%)

 


191. Prevalence and predictors of obesity among individuals testing positive for hepatitis C antibody in a multicultural, urban, tertiary care referral clinic

W. Chen; T. Wong ; G. Tomlinson; M. D. Krahn, 2; J. Heathcote

 

Background:

Obesity is considered an important factor contributing to hepatic steatosis and poor response to anti-viral therapy in patients with chronic hepatitis C virus (HCV) infection.

 

Objective:

To determine the prevalence of obesity and explore the possible factors associated with obesity in a HCV antibody positive, multicultural tertiary referral clinic population.

 

Methods:

Patient records describing visits to a downtown tertiary care liver clinic in Toronto, Canada between 1990 and 2006 were reviewed. We extracted data describing demography, life style, and mode of HCV transmission, as well as weight and height. The one sample proportion test was used to compare the prevalence of obesity in the clinic population testing positive for HCV antibody and the Canadian general population. Regression analyses and propensity score analysis (based on the propensity to test positive for HCV antibody) were applied to explore possible factors associated with obesity in this population.

 

Results:

The 1118 out of 3505 HCV antibody positive patients met our inclusion criteria. The included patients had a significantly higher prevalence of obesity (28.8% vs. 14.9%; P<0.001) than the Canadian general population. After stratification by age and gender, the clinic population remained with a significantly higher prevalence of obesity than the Canadian general population in every age/gender category. In the univariate analyses age was positively associated with high BMI (coefficients 0.073; P<0.001) and obesity (OR 1.020; 95% CI 1.003 to 1.038); Asian origin was negatively associated with BMI (coefficients -2.187; P<0.001); serum testing for positive HCV RNA was significantly associated with obesity (OR 1.731; 95% CI 1.075 to 2.788). In the multivariate regression analyses, age (OR 1.019; 95% CI 1.002 to 1.037) and serum positive HCV RNA (OR 1.798; 95% CI 1.109 to 2.917) were independent predictors for obesity. A total of 112 pairs of subjects qualified for matching by propensity score. The matched propensity score analysis demonstrated that the subjects with a positive serum HCV RNA test had significantly more obesity (32.1% vs. 18.8%; p=0.021) than those with a negative HCV RNA test.

 

Conclusion:

Age and serum HCV RNA (indicating chronic HCV infection) contribute to the high prevalence of obesity observed in a clinic population exposed to HCV.