Natural history, pathogenesis, and prevention of HCV infection

Abstract

Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV), but most of these individuals are unaware of being infected. HCV is a major cause of liver-related morbidity and mortality, and it frequently causes extrahepatic manifestations of disease. This chapter considers the natural history, pathogenesis, and prevention of HCV. This positive strand RNA virus is transmitted by percutaneous or, in very rare circumstances, mucosal exposure to HCV-infected blood. Infection targets the hepatocytes, with resultant liver inflammation and eventual fibrosis. In a subset of individuals the hepatic disease will progress to cirrhosis, placing them at risk for hepatic decompensation and hepatocellular carcinoma. Extrahepatic manifestations are seen in 10-50% of HCV-infected persons, most commonly mixed cryoglobulinemia, which is fundamentally a B cell lymphoproliferative disorder. Some individuals develop B cell non-Hodgkin lymphoma, which is usually of low-grade, although more aggressive forms have been reported. Mixed cryoglobulinemia causes a small-vessel vasculitis, manifesting as palpable purpura, arthritis, membranoproliferative glomerulonephritis, and peripheral neuropathy. Extrahepatic signs and symptoms usually regress with successful eradication of HCV. The prevention of HCV rests upon the screening of individuals at highest risk for HCV infection, coupled with appropriate risk reduction strategies to reduce viral transmission and appropriate treatment of HCV infection to reduce the potentially infectious reservoir.