Poor durability of lamivudine effectiveness despite stringent cessation criteria: A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients

Background and Aims: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B( CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen( HBeAg)-negative patients and to explore potential predictive factors. Methods: Sixty one HBeAg-negative CHB patients who had received lamivudine for at least 24 months and had maintained undetectable serum hepatitis B virus( HBV) DNAplus normal alanine aminotransferase for >= 18 months before withdrawal were included. They were followed up monthly during the first 4 months and at 3-month or 6-month intervals thereafter. Relapse was defined as serum HBV DNA >= 10(4) copies/mL. Results: Thirty one of 61 patients relapsed during follow-up, over 90% occurred within 18 months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen( HBsAg) turned negative in eight patients, and none of them relapsed during follow-up. Conclusion: Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged <= 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.