The outcome of hepatitis C is defined by the rate of spontaneous recovery from the acute infection and the impact of persistent viremia in patients who fail to recover. Persistent viremia is associated with necroinflammation of the liver and induces fibrosis progression at a rate that is determined, to some extent, by factors such as excess alcohol intake, advanced age, and immunosuppression. The endpoint of fibrosis progression is cirrhosis, which occurs only in some persons and may clinically manifest as end-stage liver disease or hepatocellular carcinoma. Based on current projections, the incidences of end-stage liver disease and hepatocellular carcinoma are expected to increase in the next decade. Therefore, future HCV natural history research is appropriately focusing on the identification of persons at risk for disease progression and evaluating the impact of treatment on the course of disease.
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