Spontaneous hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection has long been suggested as a rare event in high endemic areas. The prevalence of HBsAg in the general population of Taiwan, however, decreased remarkably from 15%-20% before age 40 to 5%-10% after age 60 or 70. This study aimed to reexamine the rates of HBsAg seroclearance by a long-term follow-up of 1965 hepatitis B e antibody-positive asymptomatic adult carriers. Of these, 1076 (55%) were males, the mean (+/-SD) age was 35.6+/-9.2 years and the mean follow-up was 10.8+/-5.4 years. Hepatitis relapsed in 314 patients, 0.5 to 18 (mean+/-SD=5.8+/-4.4) years after the entry. The probability of hepatitis relapse correlated positively with male sex (P<0.0001) and age at entry (P<0.0001). Serum HBsAg cleared in 245 patients at the mean age of 47.8+/-9.6 years. The cumulative probabilities of HBsAg seroclearance were 8.1% after 10 years, but increased disproportionally to 24.9% and 44.7%, respectively, after 20 and 25 years. In multivariate analysis, the probability of HBsAg seroclearance correlated positively with age at entry (P<0.0001) and sustained remission of hepatitis (P<0.0001) and marginally significantly with male sex (P=0.053).
Conclusion: Cumulative rate of HBsAg seroclearance in asymptomatic adult carriers from high endemic areas was approximately 40% after 25 years of follow-up. The low HBsAg seroclearance rates in previous studies might be due to the relative short period of follow-up.