Hepatitis C and cirrhosis

Hepatitis C virus infection is a common cause of liver disease worldwide and typically progresses to cirrhosis within 20 years of onset in 20% to 25% of patients. The average age at diagnosis of cirrhosis is 55 years and most patients are asymptomatic or complain of only mild non-specific symptoms such as fatigue. Approximately two-thirds of patients have hepatomegaly and one-third splenomegaly and/or peripheral manifestations of liver disease (vascular spiders or palmar erythema). At the time of diagnosis, laboratory tests usually reveal mild-to-moderate elevations in serum aminotransferases, but normal levels of serum albumin, bilirubin and prothrombin time (in 60% of patients). Once decompensation occurs, symptoms are more prominent and laboratory test results are usually abnormal. The initial form of presentation of decompensation is most commonly development of ascites. Longitudinal cohort studies of patients with compensated cirrhosis due to hepatitis C have indicated that the subsequent rates of hepatocellular carcinoma (HCC), hepatic decompensation and liver-related death are linear over time. The risk of HCC appears to vary geographically; the 4 to 5-year cumulative incidence of HCC being in the range of 7% to 11% (1.6 to 3.2 per 100 person-years) in Europe and United States but as high as 30% (6 to 7 per 100 person-years) in Japan. The 5-year cumulative incidence of decompensation is approximately 20%. Survival is reasonably good, the 4- to 5-year probability of survival ranging from 84% to 92%. Factors that correlate with prognosis in compensated cirrhosis include severity of the underlying liver disease, older patient age, older age at infection, male sex, concurrent HCV and HBV infection and excessive alcohol consumption. Most longitudinal studies suggest that the clinical impact of HCV genotype is limited. Once decompensation occurs the prognosis is poor (approximately 50% probability of survival at 5 years). The worst survival occurs in patients presenting with more than one complication, and the best in those with ascites alone. Standard regimens of alpha interferon (3 million units 3 times per week for 6 to 12 months) are less effective in inducing a sustained response in patients with cirrhosis (5% to 10%) than in patients without cirrhosis (15% to 25%). The low responsiveness is primarily related to the low initial virological response rate on therapy as well as a high rate of breakthrough. Cumulative evidence suggests that patients with cirrhosis who have a sustained virological response have an improved prognosis, especially for development of HCC. Higher dosages of interferon or combination of standard interferon with ribavirin lead to higher sustained response rates (15% to 20%). In view of these improved results, treatment can now be recommended in patients with compensated cirrhosis due to hepatitis C. The efficacy of interferon or combination therapy in decompensated cirrhosis is not documented and its use is limited by poor tolerance and side effects. On the basis of the excellent 5-year survival rates after liver transplantation (70% to 80%), patients with end-stage cirrhosis due to hepatitis C should be considered for liver transplantation.