Topic: Disease Progression 

 

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.

 

Aim:

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: 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. Rosentha1, D. Salmon; C. Lewden; F. Bonnet; T. May; P. Morla; 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: 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. Ryan1; 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%)