Benefit of lamivudine therapy and factors associated with clinical outcome in spontaneous severe acute exacerbation of chronic hepatitis B virus infection

Abstract

Objective: During the course of chronic hepatitis B virus (HBV) infection, severe acute exacerbations of the infection often occur spontaneously and follow a fulminating progression to fatal hepatic failure. The aim of this study was to clarify potential factors, including benefit of lamivudine therapy, which could influence clinical course of the serious disease in an area of intermediate HBV endemicity.

Methods and results: Using a database of 3,163 chronically HBV-infected patients, 418 (13.2%) developed acute exacerbation of hepatitis B. Of the 418 patients, 52 (12.4%) spontaneously developed severe acute exacerbation and were included in this study. Of the 52 patients, 23 were treated with lamivudine. In multivariate analyses, fulminating progression to hepatic failure (odds ratio, 15.45; 95% confidence interval, 3.71-64.41; p = 0.0002) was a significantly independent predictor of patient survival. Three variables were independently associated with fulminating development of hepatic failure: presence of cirrhosis (29.06, 1.74-85.56, 0.019, respectively), higher baseline bilirubin level (14.89, 1.31-52.91, 0.029, respectively), and genotype B (22.14, 1.59-29.68, 0.021, respectively). Treatment lacking lamivudine was a significant factor that contributed to shorter survival time, development of hepatic failure, and progression to cirrhosis in univariate analyses (p = 0.014, 0.012 and 0.0030, respectively).

Conclusion: In an area of intermediate HBV endemicity, certain proportion of chronic hepatitis B patients could spontaneously develop the serious disease. Factors influencing clinical course of the disease should be identified to improve prognosis and establish more rational and effective therapeutic strategies. Lamivudine therapy could potentially benefit the serious disease, although larger series of patients and longer follow-up periods are needed.