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 > or =200 U/L, 3% had bilirubin levels > or =2.0 mg/dL, and 5% had two or more episodes of alanine aminotransferase levels > or =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.