Spontaneous relapse of hepatitis in inactive HBsAg carriers

Abstract

Background/aims The issue of spontaneous relapse of hepatitis in anti-HBe positive asymptomatic HBsAg carriers was rarely reported before and deserves further exploration. Methods A total of 1241 anti-HBe positive asymptomatic adult HBsAg carriers were prospectively followed up. Of these, 661 (53%) were males, and the mean (±SD) age was 35.6 ± 9.1 years. Relapse of hepatitis was defined as elevation of ALT more than twice the upper limit of normal accompanied by detectable serum HBV DNA by hybridization assays. Results During a mean follow up of 12.3 years, hepatitis relapsed in 211 patients with an annual rate of 1.46%. The cumulative probabilities of hepatitis relapse were 10. 2%, 17.4%, 19.3%, 20.2%, and 20.2%, respectively, after 5, 10, 15, 20, and 25 years of follow up. Multivariate analyses showed that the probability of hepatitis relapse correlated significantly with male sex (P < 0.0001) and age at entry (P = 0.007). The cumulative probability of hepatitis relapse after 20 years was 26.9% for males and only 12.5% for females, and was 13.1% for those of age <30 years at entry but increased to 29.4% for those of age 40-49 years at entry. Conclusion Hepatitis relapsed in about 20% of asymptomatic HBsAg carries during 25 years of follow up. Relapse of hepatitis occurred more frequently during earlier years of follow up. Males were more likely to have relapse of hepatitis than females. In addition, relapse of hepatitis was significantly less frequent in patients who were younger than 30 years at study entry, possibly implicating more favorable outcome of earlier HBeAg seroconversion.

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

“…A lower annual rate of CHB relapse was reported in a recent prospective long-term follow-up study involving 1,241 incidentally identified asymptomatic, adult, inactive HBsAg carriers, for whom the date of HBeAg seroconversion was unknown and they conceivably represent later phase after HBeAg seroconversion [38]. During a mean follow-up period of 12.3 years, the annual rate of hepatitis relapse was only 1.5% and was significantly lower in those younger than 30 years at entry.…”

“…In this patient cohort, the cumulative risk of CHB relapse was also higher during the first 5-to 10-year follow-up period and decreased thereafter, becoming negligible after 20 years of follow-up. Overall, male gender, genotype C HBV infection, and delayed HBeAg seroconversion were found to be predictive factors for the reactivation of hepatitis B following HBeAg seroconversion [38]. Since the immune mechanism of HBeAg-negative hepatitis is similar to that of HBeAgpositive hepatitis, this phase with reactivation may be viewed as a variant of immune clearance phase [28].…”

Role of viral factors in the natural course and therapy of chronic hepatitis B

“…In the early 1980s, it became apparent that HBV could replicate in the absence of HBeAg, thus the fourth HBV reactivation phase was designated. Reactivation of HBV may occur spontaneously [17] or as a result of immunosuppression [18]. The annual rate of spontaneous reactivation of HBV following HBeAg seroconversion was 2.2-3.3% in Fig.…”

“…Naturally occurring mutants including mutations in precore/basal core promoter and deletion mutation in pre-S gene have been reported to be associated with progressive liver disease including development of cirrhosis and hepatocellular carcinoma asymptomatic HBsAg carriers or patients with chronic hepatitis B [13,19], while the annual rate of spontaneous reactivation in inactive HBsAg carriers was 1.5%, with a cumulative incidence of 20% after 20 years of follow up [17]. Of particular note is that reactivation of HBV in inactive carriers correlated significantly with patient age on study entry [17], suggesting a favorable outcome of earlier HBeAg seroconversion. In addition, reactivation of HBV was significantly more frequent in male gender [13] and genotype C patients [20].…”

Viral load in hepatitis B e antigen–negative carriers with normal aminotransferase level

“…6 We recently followed 1241 asymptomatic HBeAg-negative HBsAg carriers with PNALT for 14,484 person-years and found that the cumulative probability of hepatitis relapse was 5% at the 2-year follow-up and 10% at the 5-year follow-up. 8 Given these findings in earlier studies and the finding that 16% of Lin's patients had an HBV-DNA level Ͼ10 6 and 32% had a level Ͼ10 5 copies/mL, it is anticipated that the dynamic interaction between the host and HBV in these patients would result in elevated ALT level during follow-up. The finding that only mild elevation of ALT to high-normal level in their patients seems contradictory to the general concept.…”