Chronic hepatitis C.

Abstract

Infection with the hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Epidemiologic and natural history studies have helped to define the clinical impact of HCV infection, and molecular diagnostic assays have established clinical endpoints against which therapeutic regimens are currently tested. The absence of definitive therapy has generated controversy regarding indications and optimal candidacy for currently approved treatment. This paper reviews the epidemiology, natural history, clinical manifestations, diagnostic modalities, and current treatment of chronic HCV infection. Search of the MEDLINE database for English-language articles and abstracts on chronic HCV infection yielded data from more than 500 original papers, reviews, and abstracts. Hepatitis C virus is transmitted primarily through contaminated blood and less effectively by human body secretions, but a large proportion of patients have no clearly identifiable parenteral risk factors for viral acquisition. Infection with HCV results in subclinical chronic hepatitis in the majority of patients and may progress, usually over decades, to cirrhosis and hepatocellular carcinoma. Extrahepatic manifestations of HCV infection include porphyria cutanea tarda, mixed essential cryoglobulinemia, and membranoproliferative glomerulonephritis. Diagnostic modalities are accurate in estimating viral load and genotype and may be helpful in predicting and assessing response to treatment. Current therapy is limited to interferon alfa and is effective at viral eradication in only a small number of patients. The adjuvant use of drugs, such as ribavirin, in combination with interferon may hold promise at enhancing viral eradication. Understanding the mechanisms behind viral persistence and immune escape of HCV will be essential in developing effective future therapeutic and preventive strategies.