Alessia Ferrari

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.

High levels of soluble tumor necrosis factor superfamily receptors in patients with hepatitis C virus infection and lymphoproliferative disorders

BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with a variety of extrahepatic disorders that may relate to direct or indirect effects of virus infection. Increased levels of soluble forms of tumor necrosis factor (TNF) receptors I and II, found in lymphoproliferative and infectious diseases, can interfere with TNF induced apoptotic cell death. The aim of the present study was to evaluate soluble TNF family receptors levels in lymphoproliferative disorders associated with HCV infection. METHODS One hundred and forty-nine subjects were studied, including 120 anti-HCV positive patients (60 without lymphoproliferative manifestations, 47 with type II cryoglobulinemia and 13 with low-grade B-cell non-Hodgkins lymphoma (B-NHL)) and 29 anti-HCV negative subjects (19 with low-grade B-NHLs and ten normal controls). RESULTS Soluble forms of TNF receptor I, TNF receptor II and Fas were significantly higher in HCV positive patients compared with normal controls. The highest levels were found in patients affected by type II cryoglobulinemia or HCV positive lymphoplasmacytoid lymphomas (LP-NHLs), while HCV positive patients without type II cryoglobulinemia or with other B-NHLs had lower values (P < 0.01). CONCLUSIONS Among HCV infected individuals, very high levels of soluble TNF receptors are significantly associated with type II cryoglobulinemia and LP-NHLs, suggesting that they may be involved in these proliferative disorders.

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.