Hepatitis B surface antigen disappearance and hepatitis B surface antigen subtype: A prospective, long-term, follow-up study of Japanese residents ofOkinawa, Japan with chronic hepatitis B virus infection

To determine the natural course of hepatitis B surface antigen (HBsAg) disa ppearance in chronic hepatitis B virus (HBV) infection and the factors rela ted to its disappearance, 946 HBsAg carriers in Okinawa, Japan were prospec tively followed for up to 19 years (mean = 9.2 years). The disappearance of HBsAg, as determined by radioimmunoassay (RIA), was observed in 62 (6.6%) and the overall annual disappearance rate was 0.79%/year. Its disappearance was more frequent in 60 (7.4%) of 815 serum samples negative for hepatitis B e antigen (HBeAg) by RIA at entry compared with only two (1.5%) of 131 s erum samples that were HBeAg positive by RIA at entry (P < 0.05). Stepwise logistic regression analysis showed that age and HBsAg subtype were signifi cantly associated with HBsAg disappearance (both P < 0.05), and that carrie rs with subtype adr (odds ratio = 2.87) had an increased probability of cle aring HBsAg compared with carriers with subtype adw. Conversely, HBeAg disa ppearance was earlier in those with the adw subtype than in those with adr. Hepatitis B virus DNA was not detected by the polymerase chain reaction af ter HBsAg disappearance in any of the 62 from whom it had disappeared. The HBsAg titer, as measured by reverse passive hemagglutination, was related t o the time to its: disappearance; the higher the titer, the longer the time to disappearance. These findings suggest that HBeAg negativity, a more adv anced age, and low titers of HBsAg are favorable factors for HBsAg disappea rance in the natural course of chronic HBV infection. Moreover, HBsAg subty pe adr was a predictive factor for HBsAg disappearance, whereas subtype adw was predictive of early HBeAg disappearance.