Withdrawal of lamivudine in HBeAg-positive chronic hepatitis B patients after achieving effective maintained virological suppression

Abstract 

Background

A recommendation was made by the ACT-HBV Asia-Pacific Steering Committee regarding the withdrawal of lamivudine in chronic hepatitis B patients after achieving effective maintained virological suppression. The outcome of patients following this therapeutic guideline has not been clearly investigated.

Objective

In this study, we examined the outcome of patients adherent to the lamivudine withdrawal guideline.

Study design

Seventy-one chronic hepatitis B patients achieving seroconversion of hepatitis B e antigen (HBeAg) as well as effective maintained virological suppression during lamivudine therapy were included. Lamivudine was withdrawn provided that undetectable HBV-DNA had been documented on two separate occasions at least 6 months apart. The patients were followed for a median period of 15 months (range, 6–72 months). The effect of pre-therapeutic clinical and virological factors on time to relapse was analyzed.

Results

Of the 71 patients, 19 (27%) relapsed, of whom 5 showed reappearance of HBeAg and 14 had HBeAg-negative hepatitis. Cox proportional hazard model showed pre-therapeutic HBV-DNA level was the only predictor for time-to-relapse (hazard ratio=1.023, 95% confidence interval=1.004–1.043, P=0.020). Categorical analysis showed that 15/34 (44.1%) and 4/37 (10.8%) patients with pretreatment HBV-DNA levels >10⁸ and ≤10⁸copies/mL, respectively, relapsed during follow-ups. The accumulative relapse rates were significantly different between the two groups of patients (Kaplan–Meier method, P=0.003).

Conclusions

In patients with pretreatment HBV-DNA levels ≤10⁸copies/mL, lamivudine could be withdrawn after achieving effective maintained virological suppression. Relapse of HBeAg-negative hepatitis remained a major problem.

Abbreviations: ACT-HBV, advancing the clinical treatment of hepatitis B virus, ALT, alanine aminotransferase, anti-HBe, antibody to hepatitis B e antigen, AST, aspartate aminotransferase, cccDNA, covalently closed circular DNA, HBV, hepatitis B virus, HBeAg, hepatitis B e antigen, HBsAg, hepatitis B surface antigen

Keywords: Lamivudin, Hepatitis B virus, Withdrawal