Progression of liver fibrosis among injection drug users with chronic hepatitis C.

Although most hepatitis C virus (HCV) infections are acquired by injection drug use, prospective data on the progression of liver fibrosis are sparse. Baseline liver biopsies were obtained (1996-1998) on a random sample of 210 out of 1667 HCV-positive injection drug users (IDUs). Subjects were followed biannually, with a second biopsy offered to those eligible. Paired biopsies were scored 0 to 6 (modified Ishak score), significant fibrosis was defined as score 3 or greater, and progression of fibrosis was defined as an increase 2 or more units or clinical evidence of end-stage liver disease. Predictive values of blood markers [FibroSURE, aspartate aminotransferase-to-platelet-ratio index (APRI) and alanine aminotransferase (ALT)] were assessed for detection of contemporaneous and future liver fibrosis. Among 119 prospectively followed IDUs, 96% were African American; 97% HCV genotype 1a/b; 27% HIV-infected, and median age was 42 years. Most (90.7%) did not have significant liver fibrosis at first biopsy. Although predictive value for detecting insignificant fibrosis at first biopsy was greater than 95% for FibroSURE, APRI, and ALT, specificities were 88.9%, 72.7%, and 72.7%, respectively. After 4.2 years median follow-up, 21% had progression of fibrosis, which was significantly associated with serum level of HCV RNA and ALT. No serological test had predictive value greater than 40% for contemporaneous or future significant fibrosis. Even initial biopsy result had only a 30.4% value for predicting future significant fibrosis. In conclusion, significant liver fibrosis and progression were detected in some, but not most, IDUs in this cohort. In this setting with low fibrosis prevalence, FibroSURE, ALT, and APRI tests predict insignificant fibrosis; however, further work is needed to find noninvasive markers of significant liver fibrosis.

Severity and correlates of liver disease in hepatitis C virus-infected injection drug users.

Between May 1996 and June 1998, 210 members of a cohort of 1,667 hepatitis C virus (HCV)-infected injection drug users (IDUs) were selected for liver biopsy procedure after stratification based on 2 consecutive serum alanine transaminase (ALT) levels. Liver histology, which could be fully evaluated for 207 subjects, was classified by using the modified Ishak scores. At the time of biopsy, the median age of subjects was 41.3 years and the median estimated duration of HCV infection was 20.7 years; 94% were African American; 78% men; 31% were human immunodeficiency virus (HIV) seropositive; and 76% had HCV genotype 1a or 1b. Total modified histologic activity index (MHAI) scores ranged from 0 to 9, and 26.6% had a total MHAI score of 5 or greater. Persons with a total MHAI score of 5 or greater were more likely to be HIV infected (P =.04). Higher fibrosis, indicated by Ishak modified fibrosis scores of 3 to 6, was present in 10.1% of subjects and was found more often in those older than 46 years of age (the highest quartile) (P <.01). Both fibrosis scores of 3 or greater and total scores of 5 or greater were associated with elevated ALT, aspartate transaminase (AST), and gamma-glutamyl transpeptidase (GGT) levels (P <.01). When serial values were considered, the results of liver enzyme testing could reduce the probability of an IDU having a fibrosis score of 3 or greater from 10% to 3%. In conclusion, these data indicate that severe liver disease is uncommon in this urban, HCV-infected IDU cohort, especially in younger persons and those with repeatedly normal liver enzymes.