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 (%)