Geoffrey C. Farrell

Effects of Interferon Treatment Response on Liver Complications of Chronic Hepatitis C: 9-year Follow-Up Study

OBJECTIVES:Fibrotic severity, biochemical indices of poor liver function, and sporadic transmission are independent predictors of liver complications among people with chronic hepatitis C. After accounting for these factors, we tested whether interferon treatment or the treatment response reduces the rate of liver cancer, liver-related death or transplantation, and other liver complications during extended follow-up.METHODS:Liver clinic cohort of 455 patients with histologically proven chronic hepatitis C was followed prospectively for median 9 yr (IQ 6, 11 yr); 384 received interferon, 343 completed a treatment course. Liver complications were assessed in relation to treatment and treatment response in univariate and multivariate models, and survival to onset of liver-related complications was determined.RESULTS:The annual incidence of total liver complications was 1.5% in treated and 2.9% in untreated patients and appeared quasilinear throughout 9-yr follow-up. Interferon treatment did not influence the rate of liver complications. However, the rate of complications increased exponentially with transition of the treatment response from sustained viral response (SVR), through response-relapse to nonresponse (or no treatment). By univariate analysis, response to interferon treatment was a significant predictor of complications. After adjustment for fibrosis score, serum albumin concentration and mode of transmission in a multivariate model, treatment response just failed to reach significance (p = 0.058) as a predictor of outcome.CONCLUSIONS:Response to antiviral therapy, and particularly SVR, appears to reduce liver complications in chronic hepatitis C. However, in the absence of an antiviral treatment response, a course of interferon does not reduce risks of liver cancer or liver failure.

Drug-Induced Liver Disease.

Opinion statementDrug-induced liver disease can result from dosage-dependent hepatotoxicity or from adverse reactions to drugs used in therapeutic dosage. The latter idiosyncratic hepatotoxins can cause clinical syndromes that mimic all known liver diseases, so that drugs must be considered as the possible causal agent for all unexplained cases of liver disease.The only specific antidote for dosage-dependent hepatotoxicity is N-acetylcysteine (and some other sulfhydryl donors), which is highly effective for the prevention of significant hepatotoxicity after acetaminophen overdose.Early diagnosis and prompt withdrawal of the offending drug is the key to successful management of most drug-induced liver diseases.The mainstay of treatment is supportive care, with careful monitoring for signs of acute liver failure or progression to chronic liver disease.In cases of liver failure, close liaison with a liver transplant center is crucial; referral for liver transplantation should be considered if standard transplant criteria are fulfilled.Pruritus is a major symptom of drug-induced cholestasis; protracted cases may respond to ursodeoxycholic acid.Corticosteroids can be considered for cases of drug-induced hepatitis, especially those with evidence of immune hypersensitivity, if no improvement is seen in 8 to 12 weeks. Although there are no controlled trials, some patients may respond favorably.

Antioxidant levels in peripheral blood, disease activity and fibrotic stage in chronic hepatitis C.

Background: This study addressed the suggested association between levels of the antioxidants glutathione (GSH), vitamin C and vitamin E in peripheral blood and the histological activity and fibrosis stage in chronic hepatitis C (CHC). We then determined whether regular antioxidant supplementation influenced these antioxidant levels or disease severity.