Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study.

To elucidate the long-term natural course following the onset of cirrhosis in patients with chronic hepatitis B. Ninety-three patients with chronic hepatitis B who had developed cirrhosis during regular follow-up were included in this long-term follow-up study. At the time of cirrhosis detection, 30% of the patients were seropositive for hepatitis B e antigen (HBeAg) and 73% had a HBV-DNA level >10(4) copies/ml. Follow-up studies included liver biochemistry, viral markers, alpha-fetoprotein and ultrasonography every 3-6 months. During a mean follow-up period of 102 +/- 60 (12-246; median 97) months, 32 patients (34.4%) experienced 55 episodes of hepatitis flare (7.0%/year), 15 (53.6%) of 28 HBeAg-positive patients seroconverted to anti-HBe (6.3%/yr) and 12 (12.9%) lost HBsAg (1.5%/year). Overall disease progression was observed in 25 (26.9%, 3.2%/year) patients: 12 (12.9%, 1.5%/year) hepatic decompensation, 21 (22.6%, 2.7%/year) hepatocellular carcinoma and 11 (11.8%, 1.4%/year) died. Multivariate analysis showed that age at onset of cirrhosis (P = 0.015) and persistent HBeAg seropositivity (P = 0.019) were the independent factors for overall disease progression. These results suggest that patients with older age at onset of cirrhosis and persistent HBeAg seropositivity following the onset of cirrhosis were independent factors for the disease progression in the first 10-year after the development of cirrhosis in patients with chronic hepatitis B.