Strategies for assessing the long-term consequences of Hepatitis C virus infection.

The entity of non-A, non-B (NANB) hepatitis was identified in the early 1970's in the course of studies of transfusion-associated hepatitis. It was first thought to be a mild illness because most persons identified with acute hepatitis lacked symptoms, had mild enzyme elevations, and were not jaundiced. It was only after realisation that enzyme elevations persisted in almost all affected persons, and that about 20% of those undergoing liver biopsy showed fibrosis and even cirrhosis, that concern began to grow. This escalated further when it became clear that another potential outcome was evolution to hepatocellular carcinoma, a process that could take 20 to 40 years to develop. The discovery of the hepatitis C virus (HCV) in 1989 proved revolutionary, indicating that most (80% or more) of the NANB hepatitis cases were caused by this virus, and reinforcing the evidence that the majority of those acutely infected developed persistent chronic disease that could culminate in cirrhosis and even cancer. The first efforts to assess the natural history were retrospective studies that confirmed the long duration of infection, but identified a high rate of liver disease progression. Because they were conducted in tertiary care centers, the majority of patients that they studied already had potentially severe disease when first seen. Subsequent prospective studies described a more benign outcome, but most were of relatively short duration and therefore could not provide the needed long-term outcome information. Recently, a series of retrospective-prospective (non-concurrent prospective) studies involving transfusion recipients, children, women, and persons with community-acquired HCV infection suggest that evolution to cirrhosis is highly variable (2 to 20% at 20 years) and that progressive disease may be limited and not universal. Recent data suggest also that spontaneous recovery from infection may be higher than previously believed.