Background: HBV is still a worldwide health problem. Annually about 0.5-1.2 million patients die of HBV-related diseases such as liver cirrhosis and hepatocellular carcinoma. Lamivudine (LAM) is the first nucleoside analog used in the treatment of chronic hepatitis B. As LAM has been clinically used for a long time, increasing clinical experience has been achieved showing that the resistance mutation rate is relatively high. Numerous studies have also focused on the predictive factors of long-term efficacy of LAM treatment.
Objectives: To determine the optimal cutoff values of baseline hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels as predictors for the long-term efficacy of LAM treatment in patients with chronic hepatitis B.
Patients and methods: A total of 163 HBeAg-positive chronic hepatitis B patients receiving LAM treatment were recruited into the present study. Logistic regression analysis was performed to find out the independent predictors of 2-year on-treatment virological response among the baseline parameters. The receiver operating characteristic (ROC) curve was used to evaluate the optimal cutoff values of these independent predictors. The accuracy of the prediction was assessed using the area under curve (AUC) and optimal cutoff values were determined through maximizing the Youden's index.
Results: After 2 years of LAM treatment, undetectable HBV DNA was maintained in 114 (69.9%) patients. LAM-related resistance mutation (YMDD mutation) was detected in 45 (27.6%) patients. Logistic regression analysis indicated that the baseline ALT and HBV DNA levels were the independent predictors of the efficacy. ROC curve analysis suggested the integration parameter derived from the baseline ALT and HBV DNA levels had the maximal predictive value for a 2-year on-treatment virological response. The optimal cutoff values of ALT and HBV DNA were 220 IU/L and 8.2 log10 copies/mL, respectively.
Conclusions: The incidence of LAM-resistant mutations in HBeAg-positive chronic hepatitis B patients may be significantly reduced and long-term efficacy improved when the baseline ALT was greater than 220 IU/L and HBV DNA was less than 8.2 log10 copies/mL.
Keywords: Chronic hepatitis B; Drug resistance; Lamivudine; Treatment effectiveness.