核苷和核苷酸类药物治疗慢性乙型肝炎产生多重耐药的挽救治疗观察

Outcomes of nucleoside analogue-based salvage therapy in patients with multidrug-resistant chronic hepatitis B

目的探索核苷和核苷酸类药物治疗慢性乙型肝炎产生多重耐药(MDR)的挽救治疗方法。方法 2011年2月-2012年5月在本院住院及门诊产生MDR的慢性乙型肝炎患者27例,分成替诺福韦(TDF)加恩替卡韦(ETV)组、TDF单用组及阿德福韦(ADV)加ETV组。按4、12和24周时间段观察肝肾生化指标,病毒基因及HBV标志物检测值。率的比较采用卡方检验。结果TDF+ETV联合组,4周时血清肝生化检测值正常、HBV DNA检测值低于检测下限9/9例。TDF单用组,4周时血清肝生化指标复常9/9例,HBV DNA检测值低于检测下限6/9例。12周时HBV DNA检测值低于检测下限9/9例。沿用耐药时的ADV+ETV治疗组,24周未见应答。与前两组对照,χ2=5.35～6.40,P<0.01。结论 TDF可有效用于慢性乙型肝炎核苷和核苷酸类药物MDR的挽救治疗,效果优于ADV+ETV治疗。

Objective To investigate the efficacy of nucleoside analogue-based salvage therapy in patients with chronic hepatitis B（CHB） with multidrug resistance（MDR）.Methods Twenty-seven CHB patients with MDR were divided into three equal groups for receipt of salvage therapy with： tenofovir（TDF） plus entecavir（ETV）;TDF alone;or adefovir（ADV） plus ETV.Liver and kidney Over 24 weeks of treatment,the serum markers of liver and kidney function were assessed by enzymatic biochemistry analysis and the expression of hepatitis B virus（HBV） was assessed by quantitative real-time PCR and direct sequencing.The significance of intergroup differences was assessed by Chi-squared test.Results At week 4 of treatment,all patients（9/9） in the TDF＋ETV group had levels of serum liver markers and HBV DNA below the detection limit.In contrast,the four weeks of treatment with TDF alone led to normalization of serum liver markers in all（9/9） of patients but reduction of HBV DNA below the detection limit in only two-third（6/9） of the patients.The HBV DNA level was reduced below the detection limit in the remaining three patients at 12 weeks of treatment.The group treated with ADV＋ETV showed no response to treatment,even out to 24 weeks（χ2=5.35-6.40,P0.01）.Conclusion TDF alone or in combination with ETV can be an effective salvage therapy for CHB patients with MDR,and it is better than ADV＋ETV treatment.