替诺福韦酯治疗多重耐药的乙型肝炎肝硬化患者疗效初步研究

Rescue therapy by tenofovir disoproxil in hepatitis B liver cirrhotics with multiple drug resistant infection

目的探讨替诺福韦酯(TDF)治疗多重耐药的乙型肝炎肝硬化(LC)患者的治疗效果。方法 2014年10月~2016年6月我院诊治的乙型肝炎肝硬化患者80例,纳入患者在核苷(酸)类似物(NAs)治疗过程中出现多重耐药。采用随机数字表法将患者分为TDF治疗组40例和恩替卡韦(ETV)治疗组40例,均在接受TDF替换治疗12 w后,分别改为TDF或ETV继续治疗,观察48 w。结果在治疗24 w,TDF治疗组血清ALT复常率和HBV DNA阴转率分别为70.0%和82.5%,显著高于ETV治疗组的50.0%和65.0%(P<0.05);在48 w时,则分别为92.5%和95.0%,显著高于ETV组的70.0%和75.0%(P<0.05);在48 w时,TDF组血清ALT、ALB、Child-Pugh评分和肝硬度值分别为(45.6±10.4)IU/L、(35.2±1.9)g/L、(6.3±1.1)和(14.5±2.5)k Pa,显著优于ETV组【分别为(58.7±11.4)IU/L、(33.5±2.0)g/L、(7.9±1.2)和(17.5±2.8)k Pa,P<0.05】;两组肾功能和血磷水平无显著变化,病毒学突破率分别为2.5%和5.0%(P>0.05)。结论 TDF可有效抑制HBV DNA复制,持续改善患者肝功能,病毒学突破率低,对肾功能无明显影响,安全可靠,可作为多重耐药的乙型肝炎肝硬化患者有效的挽救治疗药物。

Objective To investigate the efficacy of tenofovir disoproxil（TDF） in the rescue treatment of hepatitis B liver cirrhotics with multiple drug resistant infection.Methods 80 patients with multiple drug resistant hepatitis B-induced liver cirrhosis were recruited in our hospital between October 2014 and June 2016,and they were randomly divided into two groups receiving TDF or entecavir（ETV） for rescue therapy in each 40 patients.All the patients were followed-up for 48 weeks.Results At the end of 24 weeks,serum ALT normalization and HBV DNA negativity rates in TDF-treated group were 70.0% and 82.5%,much higher than 50.0% and 65.0%,respectivley（P 〈0.05） in ETV-treated gruop;at the end of 48 weeks,they were 92.5% and 95.0%,much higher than 70.0% and 75.0%,respectively（P〈 0.05） in ETV-treated group;at the end of 48 w regimen,serum ALT,ALB,Child-Pugh score and liver stiffness measurement were（45.6 ±10.4）IU/L,（35.2 ±1.9）g/L,（6.3 ±1.1） and（14.5±2.5） k Pa,significantly different as compared to 【（58.7±11.4）IU/L,（33.5±2.0）g/L,（7.9±1.2） and（17.5±2.8）k Pa,P〈0.05】,respectively,in patients receiving ETV treatment;serum renal function index and phosphorus had no significant changes in the two groups,and viral breakthrough occurred in one（2.5%） and in two（5.0%）patients in the two groups（P〉0.05）.Conclusions TDF has the ability to effectively inhibit HBV replication,and could improve the liver functions of patients with hepatitis B-induced liver cirrhosis.It is safe and reliable and might be used as an effective alternative agent for rescue therapy for patients with multi-drug resistance infection.