NATURAL HISTORY OF HEPATITIS C

The precise natural history of hepatitis C remains unknown because of the lack of prospective data, the inability to determine time of initial onset of disease, and the variable influences of multiple cofactors leading to disease progression. What has been determined, however, is that a subset of hepatitis C patients will progress to cirrhosis and its associated complications. Chronicity is the hallmark of hepatitis C infection. Approximately 15% to 30% of patients exposed to HCV recover spontaneously, while the remaining 70% to 85% develop chronic infectioni. Most patients with chronic hepatitis C infection appear to have mild to moderate histologic disease. Cirrhosis may develop in as many as 15% to 30% of infected patients. Although fulminant disease is rare in hepatitis C, its occurrence has been reported. Several studies have attempted to determine the rate of histologic disease progression in transfusion-acquired disease. Tong and colleagues found a mean interval of 20.6 years from time of infection to development of cirrhosis, and a mean interval of 28.3 years from time of diagnosis to development of hepatocellular carcinoma (HCC).

The infusion of hepatitis C-contaminated anti-D immune globulin in 1977 and 1978 in Ireland has allowed the prospective evaluation of 376 women, 17 years after exposure. Most of the hepatitis C-infected women had evidence of moderate hepatic inflammation on liver biopsy, while 51% had fibrosis, and only 2% had cirrhosis. The results of a similar German study of 152 women infected with hepatitis C-contaminated Rh0 immune globulin showed no evidence of cirrhosis 15 years after exposure.

In a recent study published in the Annals of Internal Medicine, coworkers conducted a 45-year follow-up of hepatitis C infection in healthy young adults. In this retrospective study, stored sera from 8568 US Air Force recruits in Wyoming dating from 1948-1955 were evaluated for hepatitis C. Ten patients were found to be positive for HCV.

FACTORS INFLUENCING DISEASE PROGRAM

Several factors appear to influence the rate of progression of hepatitis C to cirrhosis. These factors include alcohol use, age at time of exposure, sex, and coinfection with either hepatitis B or HIV.

Alcohol. Alcohol ingestion and chronic hepatitis C infection appear to be synergistic in accelerating the progression of liver disease. An increased risk of cirrhosis and decompensated liver disease is associated with sustained alcohol consumption of greater than 40 g/day. Other effects of concomitant alcohol use in the setting of hepatitis C include increased transaminase levels, higher hepatitis C viral loads and increased number of hepatitis C quasispecies. These elevations have been shown to be significantly reduced with a decrease in daily alcohol intake.