基于替诺福韦酯的联合抗病毒治疗方案对应答不佳或耐药慢性乙型肝炎患者的疗效

目的 探讨基于替诺福韦酯（TDF）的联合治疗对既往核苷（酸）类似物（NAs）应答不佳/耐药的慢性乙型肝炎（CHB）患者的临床疗效。方法 对NAs应答不佳/耐药的CHB患者予以入组,给予以TDF为基础的抗病毒治疗,一组为NAs组,给予TDF＋拉米夫定（LAM）、TDF＋恩替卡韦（ETV）;另一组为干扰素（IFN）组,给予TDF＋IFN、TDF＋LAM＋IFN、TDF＋ETV＋IFN。预计疗程48~96周。比较两组患者抗病毒的疗效。结果 入组68例（NAs组41例,IFN组27例）患者基线耐药检测阳性率为77.9%。治疗48周,NAs组和IFN组乙肝病毒（HBV）DNA下降分别为（3.52±2.42）lg IU/ml、（3.62±1.29）lg IU/ml（P=0.832）,HBV DNA转阴（〈20 IU/ml）率分别为73.1%、96.3%（P=0.043）。IFN组较NAs组e抗原（HBe Ag）下降更明显[（1.07±1.30）lg COI vs.（0.35±0.98）lg COI,P=0.017]。NAs组和IFN组表面抗原（HBs Ag）下降分别为（0.09±0.61）lg IU/ml、（0.54±1.05）lg IU/ml（P=0.015）。48~96周的延长疗程中NAs组和IFN组分别有1例、3例患者出现HBs Ag转阴。结论 以TDF为基础的联合治疗方案可有效抑制病毒复制;在HBe Ag及HBs Ag转阴/转换率方面,IFN组更具优势。

The efficacy of combination therapy based on TDF in chronic hepatitis B patients with nucleos(t)ide analogues suboptimal response or resistance

Objective To evaluate the efficacy of combination therapy based on TDF in chronic hepatitis B（CHB） patients with nucleos（t）ide analogues （NAs） suboptimal response or resistance. Methods NAs suboptimal response or resistance CHB patients were divided into NAs group（TDF＋LAM,TDF＋ETV） and IFN group（TDF＋IFN,TDF＋LAM＋IFN,TDF＋ ETV＋IFN）. The treatment duration was 48-96 weeks. The antiviral efficacy was analyzed. Results Sixty-eight patients were enrolled and 77.9% of them had drug resistance. At the point of 48 weeks, the change of HBV DNA in the NAs group and IFN group was （3.52±2.42）lglU/ml, （3.62±1.29）lglU/ml, respectively （P = 0.832）. The rate of negative verology was 73.1%, 96.3% （P = 0.043）, respectively. The titers of HBeAg decreased significantly in IFN group than NAs group [（1.07±1.30）1gCOI vs. （0.35±0.98）1gCOI, P = 0.017]. The decreased titer of HBsAg at the point of 48 weeks was （0.09± 0.61）lglU/ml, （0.54±1.05）lglU/ml in the NAs group and IFN group, respectively（P = 0.015）. HBsAg negative occurred in 1 patient of the NAs group and 3 of the IFN group. Conclusion Combination therapy based on TDF in CHB patients can inhibit virus proliferation efficiently. The more important is that IFN group is superior in seroconversion of HBeAg or HBsAg.