摘要
目的 评价阿德福韦酯（ADV）和拉米夫定联合治疗方案对慢性乙型肝炎（CHB）相关性代偿期肝硬化患者的疗效和安全性.方法 2007年6月至2009年2月纳入8所医院的CHB相关性代偿期肝硬化患者,按随机代码表以1：1的比例分成初始ADV组和初始拉米夫定组.两组初始分别接受ADV或拉米夫定单药治疗.治疗第24或36周时,如果患者血清HBV DNA＞3.30 lgIU/mL或出现病毒学突破（VBT）,则加用另1种药物联合治疗.治疗第48周,所有患者均改为两药联合治疗,直至第96周.随访期间,观察患者肝硬化并发症或肝细胞癌的发生情况、病毒学应答、生物化学应答、VBT、HBV的耐药基因变异和不良反应等.统计学方法采用Fisher确切概率法.结果 206例患者在96周随访中,共17例（8.25％）发生肝硬化并发症或肝细胞癌,其中8例（3.88％）为肝细胞癌.治疗第96周,初始ADV组的HBV DNA阴转率为80.9％（76/94）,初始拉米夫定组为70.5％ （67/95）;初始ADV组ALT水平恢复正常占95.7％（90/94）,初始拉米夫定组占87.4％（83/95）;与基线比较,初始ADV组和初始拉米夫定组的血清白蛋白分别上升2.5和3.3 g/L,PT分别下降0.6和0.7s.初始ADV组VBT累积发生率为7.84％（8/102）,初始拉米夫定组为23.08％（24/104）,差异有统计学意义（Fisher确切概率法,P=0.003）.14例在治疗第96周仍未获得病毒学转阴的患者中,11例在治疗过程中曾发生VBT,其中7例存在基因变异,另4例为野生株.治疗期间的不良反应有胃肠道不适、空腹血糖升高、血压升高和头晕,经对症处理后均改善.结论 初始ADV与初始拉米夫定的联合治疗策略能防止CHB相关性代偿期肝硬化患者的肝硬化并发症或肝细胞癌的发生,并能获得持续病毒学应答和生物化学功能改善,且不良反应轻.
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＆#39; 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＆#39;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.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2014年第7期467-472,共6页
Chinese Journal of Digestion
基金
上海市卫生局重点专科课题（ZK2012801）
上海市卫生局课题（201204237）
关键词
乙型肝炎
慢性
肝硬化
阿德福韦酯
拉米夫定
联合治疗
Hepatitis B,chronic
Liver cirrhosis
Adefovir dipivoxil
Lamivudine
Combination therapy
