R. Pistis

Fibrosis progression in initially mild chronic hepatitis C

Summary.  The natural history of chronic hepatitis C presenting with no/minimal liver fibrosis is uncertain with controversies on risk of progression and need for antiviral treatment. We studied rates and determinants of fibrosis progression in initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65 ± 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively while untreated with repeated biopsy after 5 or more years (mean interval 7.8 ± 1.51 years). Patients showing fibrosis progression were compared with nonprogressors for baseline and follow‐up parameters. Sixty‐four patients (60.4%) showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1 initially. Fibrosis progression (ΔF/year) was associated with age (P < 0.0001), baseline and follow‐up alanine aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P = 0.008). Thus liver fibrosis progression occurs in two‐thirds of patients with initially mild chronic hepatitis C within 5–10 years and advanced fibrosis/cirrhosis develops in one‐third of those with F1 initially. Fibrosis is facilitated by older age and alcohol and associated with inflammatory activity and ALT levels. Antiviral therapy should be considered in mild chronic hepatitis C.

Review article: chronic hepatitis C--natural history and cofactors.

Chronic hepatitis C is highly heterogeneous in clinical presentation and outcomes.

Hepatic iron, liver steatosis and viral genotypes in patients with chronic hepatitis C

Summary.  Hepatic iron has been described in hepatitis C virus (HCV) infection as an important cofactor of disease outcome. The mechanisms leading to hepatic iron deposits (HIDs) in HCV patients are partially understood. We investigated HIDs in the liver biopsies of a consecutive series of 242 HCV‐infected patients with well‐compensated liver disease. Serum ferritin was elevated in 20.7% and transferrin saturation in 19.0%, while 38.8% had stainable HIDs indicating that serum markers of systemic iron overload have low sensitivity in predicting HIDs in hepatitis C. A cut‐off value of serum ferritin (350 μg/L in females and 450 μg/L in males) had good negative predictive value in excluding presence of mild–moderate HIDs (grade II–III). Hepatic iron deposits correlated by multivariate analysis with serum ferritin [odds ratio (OR) 1.008, 95% confidence interval (CI) 1.005–1.011] and albumin (OR 1.15, 95% CI 1.02–1.297). Hepatic iron deposits were more frequent in HCV‐3‐infected cases than in other genotypes (P = 0.027) while raised serum iron indices were more frequent in non‐HCV‐3 genotypes (P = 0.02). Furthermore, advanced fibrosis (F3–F4 by METAVIR) was more frequent in non‐HCV‐3 genotypes (P = 0.04). In HCV‐3 cases there was a close association between HIDs and severe (grade II–III) steatosis (P < 0.00001). These results indicate that in well‐compensated chronic hepatitis C HIDs are strongly associated with HCV‐3 and viral‐induced hepatic steatosis, while in the presence of other genotypes they might merely reflect a more advanced stage of liver disease and/or a systemic iron overload. Serum ferritin could identify a subgroup of patients in which the need of venesection could be excluded without liver biopsy.

Clinical trial: comparison of weekly once versus twice half-dose weekly administration of pegylated interferon alpha 2b in combination with ribavirin for the treatment of HCV-1 positive patients with chronic hepatitis C

Background  Pegylated interferon (PEG‐IFN) alpha2b is currently used as a once weekly injection in combination with ribavirin for the treatment of chronic hepatitis C.