恩替卡韦联合替诺福韦与恩替卡韦联合阿德福韦治疗拉米夫定耐药性慢性乙型肝炎患者疗效比较

目的探讨恩替卡韦(ETV)联合替诺福韦(TDF)与ETV联合阿德福韦(ADV)治疗拉米夫定(LMD)耐药性慢性乙型肝炎患者疗效,并对主要预后影响因素进行分析。方法选取在本院治疗的拉米夫定耐药的成年慢性乙型肝炎患者103例作为研究对象,其中ETV联合ADV组51例,ETV联合TDF组52例。回顾性分析患者的病历资料,包括年龄、性别、身高、体质量、体质量指数(BMI)、血小板、丙氨酸氨基转移酶(ALT)、总胆红素、清蛋白、国际标准化比值INR(IQR)、Child-Pugh评分、乙型肝炎e抗原(HBeAg)阳性数、乙肝病毒(HBV)的DNA水平、HBV的ADV耐药突变数、rtA181V/T变异、rtA181V/T+rtN236T变异、HBV的ETV耐药突变数、rtS202G变异、rtT184I/L/S变异、rtM250V/L变异及HBV的LAM、ADV及ETV耐药突变数、3~12个月患者HBV的DNA减少量及病毒学反应等信息,并进行统计分析。结果 ETV联合TDF组患者9个月HBV的DNA减少量(3.14±1.58)log10IU/mL高于ETV联合ADV组(2.31±1.84)log10IU/mL,差异具有统计学意义(P0.05);ETV联合TDF组患者12个月HBV的DNA减少量(3.28±1.62)log10IU/mL高于ETV联合ADV组(2.85±1.73)log10IU/mL,差异具有统计学意义(P0.05)。ETV联合TDF组患者6个月、9个月及12个月病毒学反应正常数均高于ETV联合ADV组患者,差异具有统计学意义(P0.05)。ETV联合TDF患者HBV的ADV耐药突变及rtA181V/T变异均低于ETV联合ADV组患者,差异具有统计学意义(均P0.05);而ETV联合TDF患者HBV的ETV耐药突变及rtS202G变异均高于ETV联合ADV组患者,差异具有统计学意义(P0.05)。ETV联合TDF组男性12个月HBV的DNA减少量高于女性(P0.05);男性患者6个月及9个月病毒学反应高于女性(P0.05)。根据多因素Logistic回归分析结果,HBV的DNA水平(OR=0.26,95%CI:0.03~0.64,P=0.015)是拉米夫定耐药性慢性乙型肝炎患者预后的危险因素,ETV联合TDF治疗(OR=98.54,95%CI:75.77~323.55,P=0.001)是拉米夫定耐药性慢性乙型肝炎患者预后的保护性因素。结论在慢性乙肝患者抗病毒疗效方面,TDF较ADV具有更强的抑制病毒活性。在对LAM和ADV应答下降的HBV感染者,TDF可能是高度有效的替代治疗药物。

Comparative study of the combination of entecavir and tenofovir with the combination of entecavir and adefovir in treatment of patients with chronic hepatitis B and lamivudine resistance

Objective To compare the effect of the combination of entecavir (ETV) and tenofovir (TDF) with the combination of ETV and adefovir (ADV) in treatment of patients with chronic hepatitis B and lamivudine (LMD) resistance and to analyze the major prognostic influencing factors .Methods A total of 103 patients with chronic hepatitis B combined with LMD resistance in the hospital from May 2010 to November 2013 were selected as the subjects ,among which ,ETV combined with ADV were 51 cases and ETV combined with TDF were 52 cases .Age ,gender ,height ,weight ,body mass index (BMI) ,platelet ,alanine aminotransferase (ALT) ,total bilirubin ,albumin ,international normalized ratio (INR) (IQR) ,Child‐Pugh score ,positive cases of HBeAg ,DNA level of HBV ,cases of ADV resistant mutation in HBV ,cases of rtA181V/T variation ,cases of rtA181V/T and rtN236T mutation ,cases of ETV resistance mutation in HBV ,cases of rtS202G variation ,rtT184I/L/S variation ,rtM250V/L mutation ,cases of LAM ,ADV and ETV resistance mutation ,DNA reduction of patients with HBV from 3 to 12 months and virological response were analyzed . Results DNA reduction in the group of ETV combined with TDF (3 .14 ± 1 .58)log10 IU/mL was significantly higher than that in group of ETV combined with ADV (2 .31 ± 1 .84)log10 IU/mL (P<0 .05) .DNA reduction in the 12th month of ETV combined with TDF (3 .28 ± 1 .62)log10 IU/mL was significantly higher than that of group of ETV combined with ADV (2 .85 ± 1 .73)log10 IU/mL (P<0 .05) .The rates of virological response normally in the 6th ,9th and 12th month of the ETV combined with TDF group was significantly higher than of the ETV combined with ADV group (P< 0 .05) .Rates of ADV resistance mutation and rtA181V/T variation in the group of ETV combined with TDF were significantly higher than that of ETV combined with ADV (P<0 .05) .While the rate of ETV resistance mutation in group of ETV combined with TDF was significantly higher than that of ETV combined with ADV (P<0 .05) .DNA reduction of male patients was significantly higher than that of female patients in ETV combined with TDF group in the 12th month(P<0 .05) ,and the rates of virologitcal response of the male patients in the 6th and 9th month were significantly higher than that of female patients (P<0 .05) .Levels of DNA of HBV was the risk factor for the prognosis of patients with with chronic hepatitis B and lamivudine resistance (OR=0 .26 ,95% CI:0 .03-0 .64 ,P=0 .015) and the treatment of ETV combined with TDF was the protective factor (OR=98 .54 ,95% CI:75 .77 -323 .55 ,P=0 .001) .Conclusion TDF could inhibit the activity of the HBV better than ADV in the treatment of patients with chronic hepatitis B .For the patients with the decreased response for LAM and ADV ,TDF may be the effective alternative drug .