Efficiency and safety of lamivudine and adefovir dipivoxil combination therapy for ninety-six weeks in patients with chronic hepatitis B associated compensated liver cirrhosis

Abstract

Objective To evaluate the efficiency and safety of lamivudine (LAM) and adefovir dipivoxil (ADV) combination therapy in patients with chronic hepatitis B (CHB) associated compensated liver cirrhosis.Methods From June 2007 to February 2009,patients vith CHB associated compensated liver cirrhosis of eight hospitals were enrolled.According to random code table,these patients were divided into initial LAM group and initial ADV group in 1:1 ratio.Patients of the two groups received ADV or LAM monotherapy initially.At week 24 or week 36 of treatment,if the serum hepatitis B virus (HBV) DNA level of patients exceeded 3.30 lglU/mL or virological breakthrough (VBT) occurred,the other medicine was added for combination therapy.At week 48,the treatment of all the patients was changed to two medicine combination therapy till week 96.During follow-up period,the occurrences of complications of liver cirrhosis or hepatocellular carcinoma,virological and biochemical responses,VBT,HBV drug resistance gene mutations and adverse reactions were observed.Fisher' s exact test was performed for statistical analyses.Results Among the 206 patients and in 96 weeks' follow-up,a total of 17 cases developed complications of liver cirrhosis or hepatocellular carcinoma and in which eight cases were hepatocellular carcinoma (3.88％).At week 96 of treatment,HBV DNA negative convertion rate of initial ADV group was 80.9％ (76/94) and that of initial LAM group was 70.5％ (67/95).The alanine aminotransferase (ALT) levd normalization rate of initial ADV group was 95.7 ％ (90/94) and that of initial LAM group was 87.4％ (83/95).Compared with the baseline,the serum albumin level increased 2.5 and 3.3 g/L,respectively,and the prothrombin time shortened 0.6 and 0.7 seconds,respectively.The accumulated VBT rate of initial ADV group was 7.84％ (8/102) and that of initial LAM group was 23.08％ (24/104),the difference was statistically significant (Fisher's exact test,P=0.003).Among 14cases without virus negative convertion at week 96 of treatment,11 cases developed VBT during treatment and in which seven cases were with gene mutations and the other four cases were wild strains.During treatment,adverse reactions included abdominal discomfort,elevated fasting blood glucose,high blood pressure and dizziness,which improved after symptomatic treatments.Conclusion Both ADV and LAM initiated combination therapy can prevent the occurrences of complications of liver cirrhosis or hepatocellular carcinoma in patients with CHB associated compensated liver cirrhosis,and furthermore,it obtains sustained virological response and biochemical function improvement,with slight adverse reaction. Key words: Hepatitis B, chronic; Liver cirrhosis; Adefovir dipivoxil; Lamivudine; Combination therapy