Viral Hepatitis Posters Saturday 2 pm

HIV/HCV Coinfection

502. Liver Histology In HIV/HCV Coinfected Patients With Persistently Normal Serum Aminotransferases.

C. Sagnelli; C. Uberti-Foppa; L. Galli; G. Pasquale; N. Coppola; A. Masiello; L. Albarello; C. Doglioni; A. Lazzarin; E. Sagnelli

Brief background and aim:

We studied 34 HIV/HCV coinfected patients with normal aminotransferases in 9 determinations in 18 months (we named C-PNAL group) who underwent percutaneous liver biopsy (LB) in comparison with 30 HCV-monoinfected patients with PNAL (HCV-PNAL group) who underwent liver biopsy in the same period. No patient had received anti-HCV treatment before liver biopsy.

Material and methods:

Liver biopsies were analysed for HAI, fibrosis and steatosis (Ishak’s scoring system) by a pathologist unaware of clinical and laboratory data. Several microlesions were recorded as present or absent: i.e. acidophil bodies, lymphoid follicles; dysplasia, rhomboid hepatocytes, Mallory’s bodies, germinative centres, etc.

Results:

There were 34 patients in the case group and 30 patients in the control group. At the time of liver biopsy, 29 of the 34 patients in the C-PNAL group were in HAART and 5 untreated. Compared to patients in the HCV-PNAL group those in the C-PNAL group more frequently were males (61.7% vs 43.3%,p<0.0001), IVDAs (76.5% vs 0%, p<0.0001) and with HCV-genotype 3 (38.2 vs 0% ,p<0.0001) or 4 (29.4%,vs 0%, p<0.0001). The C-PNAL group showed a good immunological assessment (mean±SD CD4 564±314), but the nadir of CD4 was ≤200 cell/mL in 52.9% of cases. The HAI score was <8 in the majority of cases in both groups (91.2% vs 96.7%), but the fibrosis score was higher in the C-PNAL group (mean±DS 2.1±1.5vs1.4±0.6, p<0.05), with a degree of fibrosis from 3-6 more frequent in the C-PNAL group (23.5% vs 6.6%,p<0.05). The higher degrees of steatosis (scores 3-4) were found more frequently in the C-PNAL group, (32.3% vs 3.3%, p<0.005) possibly due to HAART or to the high frequency of cases with HCV-genotype 3. The analysis of liver microlesions did not show differences statistically significant between the two groups of patients investigated.

Conclusions:

· The data indicate that both HIV/HCV coinfected and HCV-monoinfected patients with PNAL show a low degree of necroinflammation; patients with HIV/HCV coinfection frequently show moderate or high liver fibrosis and deserve anti-HCV treatment.

· The analysis of overlapping liver lesions show a few differences significant to statistical analysis of uncertain clinical and prognostic value suggesting further investigation is necessary.

HIV/HCV Coinfection

503. An On-going Outbreak of Acute HCV in HIV-infected Men in New York City: Rates of Spontaneous Clearance and Treatment Responses.

A. J. Uriel; D. S. Fierer; D. C. Carriero; A. L. Klepper; S. Fishman; S. Factor; M. Fiel; S. N. Thung; M. P. Mullen; D. T. Dieterich; A. D. Branch

Background:

Factors influencing spontaneous clearance (SC) of acute hepatitis C (HCV) in HIV positive subjects are not well characterised. Recent data suggests sexual exposure is associated with increased SC of HCV. Higher sustained viral response (SVR) rates are seen if these subjects are identified and treated in the acute rather than chronic phase of HCV infection.

Aim:

To assess the rate of spontaneous clearance of HCV, and response to therapy with Pegylated interferon (PegIFN) and ribavirin (RBV) in a prospectively enrolled cohort of HIV+ men who have sex with men (MSM) infected during the ongoing outbreak of acute HCV in NYC.

Methods:

Data were collected on 22 men (23 episodes) consecutively enrolled between 1/05 and 4/08 (inclusion criteria – new ALT elevation and >10X fluctuation in HCV RNA and/or HCV seroconversion). Sontaneous clearance was defined as HCV RNA persistently < 600IU/ml for > 6 months (m) post diagnosis. Patients with HCV RNA > 600IU/ml after follow up (FU) for up to 6 months received PegIFN/RBV. RVR, EVR, and SVR were defined as HCV <600IU/ml after 4 wks and 12 wks of PegIFN/RBV and at 24 wks post therapy, respectively. Clinical variables including age, ethnicity, HCV risk factor (RF), anti-retroviral therapy (ART), CD4 count and HIV RNA , peak bilirubin, ALT and HCV RNA, and symptomatic vs. asymptomatic presentation were compared between patients with and without spontaneous clearance using Students t and Fishers exact tests.

Results:

Median age 41.5 (29 -49) years, 45% were Caucasian, 41% Hispanic and 14% African American. All had HCV genotype 1. Median CD4 count was 499 (223-969) cells/mm3; 70% were on ART; 43% had detectable HIV RNA.HCV RF was high risk sexual activity alone in 18/23 (78%) cases, IVDU was the main RF in 5; 11/23 (48%) episodes were symptomatic. spontaneous clearance occurred in 4/23 episodes (17%). PegIFN/RBV was started in 16 patients, 12 have data after week 4(2 lost to FU); 11/12 had HCV RNA < 600 IU/ml after a median of 6 (2 -12) wks. RVR occurred in 6/12 (50%); EVR in 9/10 (90%) and SVR in 6/8 (75%) evaluable patients. No significant difference was seen between patients with and without spontaneous clearance, although there was a trend toward higher peak ALT levels in patients who failed to clear spontaneously (p=0.165). One patients with genotype 1b HCV who achieved SVR became newly infected with a genotype 1a infection following a relapse into IVDU.

Conclusions:

Spontaneous clearance was seen in 17% of the episodes of acute HCV in HIV + MSM; spontaneous clearance was not associated with sexual exposure as the risk factor for HCV. SVR with PegIFN/RBV was achieved in 75%. The occurrence of a second episode of acute HCV in one subject underscores the need for continuing surveillance and better strategies to modify high risk behaviour in this population.

NIHDA016156/DKO66939

Disease Progression – Diabetes

505. High RNA HCV as Associated Factor to Hyperglycemia in Hepatitis C Chronic Patients.

J. A. Mata-Marin

Introduction:

There were noted glucose metabolism alterations in hepatitis C chronic patients; in this situation the expression of HCV proteins increase the production of TNF- α and avoid tirosin-phosphorilation at insulin receptors; this causes insulin resistance and increase in glucose. High RNA VHC could be correlated with hyperglycemia in this patients.

Objective:

To stablish the association between RNA HCV with hyperglycemia in hepatitis C chronic patients.

Setting:

“Hospital de Infectología” National Medical Center “La Raza” DF., Mexico City.

Design:

Correlation cross-sectional design.

Methods:

We evaluated hepatitis C chronic patients; they were clinically evaluated and we checked several biochemical parameters such as: RNA HCV (COBAS AMPLICOR HCV TEST, V2.0 with detection limit 50 UI/ml ); complete blood count, liver panel, basic metabolic and electrolyte panel, finally, we testing genotype obtained by PCR.

Statistical analysis:

We used descriptive statistical; Pearson correlation coefficient (r)and lineal regression to stablish independence among variables.

Results:

90 patients were included in the study. Mean age (±SD) was 43.14 years old (± 12.2); weigth 70.6 kg (± 11.0); Hemoglobin 14.7 g/dl (± 1.9); Glucose 102.6 mg/dl (± 19.9); Albumin 4.4 g/dl (± 0.5); ALT 76.4 UI/dl (± 59.9); RNA HCV 2097354.5 (± 6822070.9) and APRI index 1.31 (± 0.4). 27(30%) patients had fasting abnormal glucose (>100 - <126 mg/dl); 7 patients had hiperglucemia (> 126 mg/dl). We realize Pearson correlation coefficient finding a positive correlation between RNA HCV and glucose (r = 0.211; p = 0.05). After adjust with lineal regression including all the variables that could potentially modify the result, this association remains significant.

Conclusion:

There is a correlation between High RNA HCV and hyperglycemia in hepatitis C chronic patients.

Table 1. Basal characteristics

	Age (years)	Weight (kg)	Hemoglobin (g/dl)	Glucose (mg/dl)	Albumin (g/dl)	ALT (UI/ml)	RNA HCV (UI/ml)	APRI index
N Valid Missing Mean Std. Error of Mean Median Std. Deviation Range Minimum Maximum	90 0 43.14 1.289 44.00 12.230 55 19 74	90 0 70.66 1.163 70.00 11.034 53 47 100	90 0 14.770 .2104 15.000 1.9963 10.9 8.1 19.0	90 0 102.656 2.1062 98.000 19.9815 100.0 72.0 172.0	90 0 4.446 .0551 4.500 .5228 2.8 2.9 5.7	90 0 76.456 6.3220 53.000 59.9753 235.0 14.0 249.0	90 0 2097354.56 719109.422 543500.00 6822070.982 55998800 1200 56000000	90 0 1.31 .052 1.00 .466 1 1 2

Epidemiology and Transmission Issues - General

507. Title: Prevalence of Chronic Viral Hepatitis in South Asians Immigrants – People from Pakistan have high rates of infection with hepatitis C and high rates of hepatitis C induced cirrhosis in middle age.

G. Uddin; G. R. Foster

Introduction:

Viral hepatitis is common in South Asia (the Indian sub-continent) where infection is believed to be acquired in childhood. We have studied the prevalence in South Asians living in the UK and in this unselected population we have assessed the rates of advanced liver disease.

Methods:

HBV and HCV prevalence was assessed by oral fluid testing of asymptomatic volunteers attending local religious and community centres. Positive tests were reconfirmed at local hospitals. Cirrhosis or advanced liver disease was identified by ultrasound scan or liver biopsy.

Results:

We have screened over 4,000 first generation Bangladeshi, Pakistani and Indian people (all born outside the UK) . Hepatitis C is rare in Indians (1/985) and Bangladeshis (3/782 - 0.38%) but common in Pakistanis 3.06% (54/1763). Hepatitis B was uncommon in all communities – 0% in Indians, 1% in Bangladeshis and 2% in Pakistanis.

We are completing an assessment of liver disease severity in those found to be infected with hepatitis C in this community survey. To-date 20 patients have undergone liver biopsy – the prevalence of cirrhosis increases with increasing age – and >80% of patients aged 50-60 years had cirrhosis. However the proportion of patients with cirrhosis decreased with advancing age such that patients over the age of 70 (N= 1) rarely had cirrhosis. Elderly patients without cirrhosis did not differ from other patients in terms of their duration of stay in the UK and in terms of their risk factors for infection. Studies of hospital admissions during the last two years confirm that most Pakistani patients with decompensated cirrhosis were aged between 50-60 years old. These data are compatible with a model of hepatitis C disease progression where most patients develop cirrhosis within 50 years of infection but a small cohort have non-progressive disease over many decades.

Conclusion:

Chronic viral hepatitis in immigrants from Bangladeshi and India is uncommon but common in people from Pakistan. In Pakistanis, presumably infected in early childhood, cirrhosis is common in middle age but the rate of cirrhosis then declines, suggesting that some patients develop non-progressive disease.

HCV Drug Pipeline- General

510. Consistent Results For Antiviral Activity And Safety Of Sustained Release Interferon-Alpha-2b (IFN-Alpha-2b XL) Compared To Marketed IFN-Alpha-2b And Its Pegylated Form (Peg-IFN-Alpha-2b) In Two Phase I Trials In Hepatitis C (HCV) Patients.

C. Trepo; R. Rouzier; C. Raffanel; M. Maynard-Muet; H. Belhadj-Tahar; M. Bourliere; Y. Donazzolo; P. Pradat; P. Berthillon; M. Guest; J. Grassot; R. Meyrueix; F. Nicolas; R. Kravtzoff

Background and Aims:

A novel formulation of human recombinant interferon (IFN) based on Medusa® technology (IFNα-2b XL) was designed to provide a sustained release pharmacokinetic profile with the aim of achieving a similar antiviral activity while improving safety versus current reference drug Peg-IFNα-2b. Two phase I clinical trials were carried out to determine the therapeutic potential and the safety of IFNα-2b XL, as compared with marketed IFNα-2b and Peg-IFNα-2b.

Methods:

Study 1 was a phase I, dose-escalating study in 84 HCV patients allocated to either regular IFNα-2b 3MIU thrice-in-week or IFNα-2b XL 9MIU, 18MIU, 27MIU, or 36MIU once-a-week. Study 2 was a phase Ib, randomized, parallel groups study conducted in 37 HCV patients allocated to either IFNα-2bXL 18MIU, IFNα-2bXL 27MIU, or Peg-IFNα-2b 1.5 µg/Kg, both administered sequentially at one week interval. The pharmacodynamics and pharmacokinetics following each administration of each treatment were monitored during each 7-day post-dosing periods, i.e. up to day 14 in study 2.

Results:

In both studies the sustained release was confirmed with a long apparent terminal half-life suitable for weekly dosing. The relative bioavailability of IFNα-2b XL was 19% to 54% versus regular IFNα-2b. As compared with Peg-IFNα-2b, there was a significant decrease in AUC and Cmax by 7 to 17 folds.

The residual antiviral activity at day 7 following IFNα-2b XL injection was remarkably consistent within the two studies (-0.28 and -0.21 log for IFNα-2b XL 27MIU versus corresponding -0.06 for Peg-IFNα-2b in genotype 1 non-responder patients). Moreover IFNα-2b XL displayed a significant antiviral treatment-effect, with IFNα-2b XL 27MIU resulting in a greater antiviral activity than Peg-IFN at day 14 (-0.61 versus. -0.21 log, p<0.05).

In both studies IFNα-2b XL was associated with a reduced mean number of treatment-related adverse events (AEs)/patient (IFNα-2b XL 27 MIU 3.7 to 5.3 AEs/patient versus regular IFNα-2b 5.2 and Peg-IFNα-2b 7.6), including less systemic treatment-related AEs (i.e. fever and white blood count abnormalities). No serious AEs occurred in any group.

Conclusions:

IFNα-2b XL has an antiviral activity at least similar to that of referent Peg-IFNα-2b and displays a consistent efficiency and safety profile within these two studies. IFNα-2b XL now requires to be further investigated foreseeing a favourable benefit/risk ratio versus current marketed therapy in a pivotal phase II design.

Epidemiology and Transmission – General

516. Characteristics of hepatitis delta in northern California.

D. Yi; S. F. Baqai; R. G. Gish

Aim:

To assess characteristics, including clinical presentation, country of origin, rate of HCV co-infection, and viral load of patients with hepatitis delta in northern California.

Methods:

In this study, 55 patients who were positive for HBsAg and hepatitis D virus (HDV) antibody were included. A cross-sectional approach reviewing chart and laboratory data was utilized.

Results:

Overall there is male dominance, in which 43 (78%) patients out of 55 were male and 12 (22%) out of 55 patients female. The country of origin for the patients was predominantly United States (60%) but there were also 5 (9%) patients of Chinese origin and 3 (5%) patients of Vietnamese origin. The remaining patients were from other countries within Asia, Africa, Middle East, and Eastern Europe. The mean age at time of presentation was 46. Patients of a wide age range were affected by hepatitis delta (median 47.0 years, range 19-79). Of the 55 patients, 45 (82%) patients had hepatitis C virus (HCV) antibody test results.18 (40%) of 45 were co-infected with HCV and 27 (60%) patients were not. Hepatitis B virus (HBV) DNA was detectable in 43 (78%) patients and negative in 8 (15%) patients. 3 (6%) patients were found to have HBV DNA levels >100,000 IU/mL.

All of the hepatitis delta patients were extracted from a prior study conducted by this collaboration. In the study, there were 1,191 chronic HBV carriers. 55 (4.62%) of the total chronic HBV population were HBV/HDV co-infected and 18 (1.51%) were HBV/ HCV/HDV infected. 32 (58%) of 55 patients carried a diagnosis of cirrhosis compared to 262 (22%) of 1191 chronic HBV patients. 13 (72%) HCV co-infected patients had evidence of cirrhosis while 4 (22%) patients did not.

Conclusions:

HDV affects individuals of all ages, primarily males. Individuals with HBV/HDV co-infection have higher rates of cirrhosis. Individuals with HBV/HCV/HDV infection have rates of cirrhosis significantly higher than individuals with either chronic HBV infection or HBV/HDV co-infection. Testing for HDV should be performed in patients with advanced liver disease or high risk behavior.

HCV Treatment – General

520. Sustained virological response (SVR) to pegylated interferon and ribavirin has no effect on neurocognition and cerebral metabolite levels in patients with chronic hepatitis C.

V. Pattullo; M. McAndrews; M. Mrkonjic; A. Damyanovich; E. Heathcote

Aim:

To determine the effect of antiviral treatment on neurocognition, quality of life, fatigue score and cerebral metabolites in subjects with chronic hepatitis C (CHC).

Methods:

Pre and post standard antiviral therapy with pegylated interferon and ribavirin, fifty non-cirrhotic patients with treatment naïve CHC, rigorously screened for other causes of impaired cognition, were assessed using neurocognitive tests, quality of life and fatigue questionnaires and cerebral magnetic resonance spectroscopy (MRS). Post-treatment results were compared with those at baseline. The same assessments were made at baseline and a year later in healthy controls. Chi-square and t-tests were used to compare CHC responders and non-responders to controls at baseline and at post-treatment time-points. Repeated measures ANOVA were used to determine whether the magnitude of change observed over time differed between the study groups.

Results:

Thirty-four (68%) of the 50 patients treated for CHC achieved an SVR. Thirty-one of 34 responders and 10 of 16 non-responders consented to repeat neurocognitive testing, self-report questionnaires and MRS.

Neurocognition, quality of life and fatigue: There was no significant difference in any score between the 31 responders and 10 non-responders at baseline or after therapy. While patients with CHC had lower memory scores and higher depression and fatigue scores than controls at baseline, no statistically significant group x time interactions were demonstrated for the change in these parameters in the 31 CHC responders compared with the 40 controls at repeat testing.

Cerebral MRS:

Cerebral MRS failed to demonstrate a significant difference in central white matter choline in patients with CHC compared with controls at baseline. While group x time interactions were demonstrated in 8 of the 15 measured cerebral metabolite values, these appeared to represent regression to the mean, as the absolute levels in patients with CHC remained relatively constant after SVR was achieved.

Conclusions:

Successful viral clearance in patients with CHC results in modest but non-significant improvements in memory, quality of life and fatigue and no significant change in cerebral metabolite levels. These findings suggest there is minimal effect of the hepatitis C virus on central nervous system integrity or quality of life in a carefully selected cohort that appeared to be free of other medical and/or psychiatric comorbidities. Unfortunately, a substantial proportion of patients who were non-responders to therapy were lost to follow-up and these individuals may carry a higher burden of neurocognitive dysfunction and impaired quality of life.

HCV Treatment – General

521. Hepatitis c among HEAVY ALCOHOL CONSUMERS : Does it require treatment?

M. Pascal; M. Marie; S. Maud; G. Michel

Background:

Alcohol consumtion is still a limit for treating hepC. A consumption over 30g per day is still a brake for bitherapy regarding consensus conferences of 2002 in France and US.

Aim:

Evaluate the impact of screening, diagnosing and treating hep C among a french group of alcohol abusers.

Methods:

During 5years (between 1997 and 2002(, In St Dizier Champagne, France, 513 patients (3/4 male, 1/4 female) were consecutively hospitalized for alcohol withdrawal therapy. Their virological status, level of fibrosis, origin of infection and alcohol abuse patterns were prospecrtively collected. Hep C treatment was proposed to every viremic patient. Frequency of hepatitis C , impact of treatment in terms of virological response and fibrosis were analysed.

Results:

Notably, a prevalence of 4,9% positive test in the group strongly indicates that alcohol consumers concentrate a high risk population facing HCV infection. Upon 28 viremic patients, 17 were treated by the combination of Pegylated Interferon+ Ribavirin. Above them 72%, (n=12) had a Sustained Viral response (SVR). Moreover, during the treatment period, they were likely to improve their level of fibrosis according to a safer drinking behavior.

Conclusion:

Heavy alcohol consumption, while requiring a long term cooperative therapy, involving pluridisciplinary setting, appears to be a major Public health target for the future of Hepc Treatment.