Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B

Abstract

Background: The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown. Methods: Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine amino-transferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls. Results: Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for ≥6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment (P=0.02). Conclusion: Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine. © 2008 International Medical Press.