Patterns of progression: unpredictability and risk of decompensated cirrhosis.

Hepatitis C virus (HCV) infection appears to have a slow but progressive evolution to chronic hepatitis and cirrhosis in a significant percentage of patients. Chronic hepatitis develops in 60-80% of patients. Worldwide prospective studies have shown that a further 20-30% of patients with chronic active hepatitis will develop cirrhosis regardless of the possible source of HCV infection. The percentage of cirrhotics is generally believed to increase progressively as the length of follow-up increases. In patients with chronic HCV, there also is high risk for the development of hepatocellular carcinoma. Factors influencing the rate of progression from chronic hepatitis to cirrhosis appear to include age at time of exposure, duration of infection, degree of liver damage at initial biopsy, immunological status, and possibly HCV genotype. The mean intervals between the time of initial infection and the diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma have been estimated to be 10, 20, and 30 years, respectively. The progression of disease is variable and is not always orderly and sequential. Patients can progress from chronic persistent hepatitis or chronic active hepatitis directly to hepatocellular carcinoma without first developing cirrhosis, especially those with genotype 1b. In addition, cirrhosis does not appear to lead to clinically apparent hepatic failure in all patients. Because of the variability in the clinical presentation and clinical progression of chronic HCV, long-term follow-up studies may be necessary to fully assess the sequelae of chronic HCV infection. Most patients with chronic HCV have abnormal liver histology but can present as otherwise healthy individuals. In contrast, patients with chronic HCV who have normal hepatic chemistries can have substantial hepatocellular damage. Consequently, treatment at diagnosis offers the greatest likelihood of eliminating the virus and preventing progression to more severe liver disease.