Natural Course of Anti-Hbe Positive Hbsag Carriers---Reactivation of Hepatitis B, HbSAg Seroclearance and Cirrhosis

Hepatitis B virus (HBV) infection is highly endemic in Taiwan, where the HBsAg carrier rates in the general population are high up to 15% to 20% before the era of universal nation-wide neonatal HBV vaccination. The natural history of chronic HBV infection consisted of four chronological phases: (1) Immune tolerance phase: HBeAg positive with normal ALT; (2) Immune clearance phase: HBeAg positive with raised ALT; (3) Inactive carriers: anti-HBe positive with normal ALT; and (4) Reactivation of hepatitis B: HBeAg-negative chronic hepatitis B. Most HBsAg carriers are incidentally identified during blood donation or health check up. Among them, the great majority is negative for HBeAg and has normal ALT. For example, in one large series of 10431 incidentally identified asymptomatic adult HBsAg carriers from Taiwan, 19.6% were HBeAg positive and 80.4% were HBeAg negative. Of the latter, only 16.2% had abnormal ALT. It is thus estimated that 67% of incidentally identified asymptomatic HBsAg carriers in Taiwan are anti-HBe positive and have normal ALT. The natural course of chronic HBV infection in these anti-HBe positive asymptomatic HBsAg carriers, however, has rarely been reported before and deserves further study. From 1980 till now, asymptomatic adults who were incidentally identified as HBsAg carriers during blood donation or health check up were recruited into the present study if they fulfilled the following criteria: (1) HBsAg positive for at least one year; (2) HBeAg negative, anti-HBe positive, normal ALT (0-36 U/l), no evidence of cirrhosis based on the clinical ground and liver ultrasonography and no concomitant infection with hepatitis C virus or hepatitis D virus at baseline; (3) no anti-viral or immunomodulatory therapy before study entry and during follow up; (4) regular follow up at least every year and for a minimum of 3 years. Patients who had alcohol or drugs that might be possible etiological agents of hepatitis were excluded. A total of 2000 to 2500 patients have been followed for 3 to 25 years. The major clinical events during follow-up periods including reactivation of hepatitis B, HBsAg seroclearance and progression to cirrhosis based on clinical grounds and ultrasonography, were recorded. Estimates on the rate of progression to cirrhosis B were calculated by the actuarial analysis method. Univariate and multivariate Cox proportional hazards regression models were performed to identify factors associated with progression to cirrhosis. Finally, the risk of cirrhosis in HBsAg carriers with reactivation of hepatitis B was correlated with precore stop mutant and basal core promoter mutant of HBV.

Project ID:PC9709-0934
External Project ID:NSC97-2314-B182-019-MY2