Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels

Background Natural history studies of hepatitis B virus infection have shown relapse of hepatitis in 5% to 15% of patients and progression to cirrhosis in 2% to 6% annually. Follow-up of patients beginning at the early phase of infection might provide data with less referral bias than in previous studies. Methods Test of liver biochemistry, assessment of virological markers, and ultrasound examinations were performed at regular intervals during the course of hepatitis B e antigen (HBeAg) to antibody (anti-HBe) seroconversion in 240 HBeAg carriers with normal alanine aminotransferase levels at baseline. Factors predictive of cirrhosis were identified by multivariate analysis. Results We enrolled 130 men and 110 women. The mean (± SD) age at entry was 27.6 ± 6.2 years. During the HBeAg-positive phase, 29% of patients had alanine aminotransferase levels ≥200 U/L, 3% had bilirubin levels ≥2.0 mg/dL, and 5% had two or more episodes of alanine aminotransferase levels ≥200 U/L. The mean age at anti-HBe seroconversion was 31.3 ± 7.0 years, with remission of hepatitis in all patients. However, hepatitis recurred in 36 patients (15%), with an annual rate of 2.2%. Thirteen patients (5%) progressed to cirrhosis. The annual incidence of cirrhosis was 0.5%, and the cumulative probability of cirrhosis after 17 years was 12.6%. Age at anti-HBe seroconversion and relapse of hepatitis were independent risk factors for cirrhosis. Conclusion The clinical severity of chronic hepatitis B was milder in this cohort than in previous studies. Delayed HBeAg seroconversion and relapse of hepatitis were associated with increased risk of cirrhosis.