替诺福韦酯治疗恩替卡韦耐药和应答不佳慢性乙型肝炎的临床观察

Clinical efficacy of tenofovir treatment on entecavir-resistance or poor-responsive chronic hepatitis B patients

目的探讨对恩替卡韦应答不佳和耐药的慢性乙型肝炎采用替诺福韦酯治疗的效果。方法选取2016年3月至2019年4月在联勤保障部队906医院温州医疗区就诊的慢性乙型肝炎对恩替卡韦治疗应答不佳患者(A组)36例,对恩替卡韦耐药(B组)44例,均换用富马酸替诺福韦酯单独抗病毒治疗,观察治疗12、24、48周的HBV DNA转阴率,肝肾功能指标的变化,不良反应发生率。结果替诺福韦酯治疗12、24和48周时,A组HBV DNA低于检测下限的比例分别为66.66%(24/36)、83.33%(30/36)、94.44%(34/36),均高于B组40.90%(18/44)、72.72%(32/44)、86.36%(38/44),在12周时差异有统计学意义(χ^(2)=5.27,P=0.028),在24周、48周时差异无统计学意义(χ^(2)=1.27、1.43,均P>0.05)。12周时A组肝功能复常率75.00%(12/16)高于B组的33.33%(8/24)(χ^(2)=6.67,P=0.019),在24周、48周差异无统计学意义(P>0.05)。2例出现恶心、呕吐,1例出现血磷轻度下降,未见明显肾损伤。结论替诺福韦酯抗病毒疗效显著,对恩替卡韦耐药和应答不佳的患者可及时换用此药,延缓病情进展和演变。

Objective To investigate the clinical efficacy of Tenofovir dipivoxil(TDF)treatment on chronic hepatitis B patients with entecavir(ETV)resistance or poor-responsiveness.Methods Seventy chronic hepatitis B(CHB)patients collected from the 906th Hospital of Chinese PLA between March 2016 and April 2019 were enrolled in this retrospective case-control study.The patients were all poor responsiveness to initial ETV treatment.They were further divided into ETV poor-responsive group(group A,N=36)and ETV-resistance group(group B,N=44).All patients were shifted to TDF treatment alone for 48 weeks.The undetectable rate of HBV DNA,the alteration of liver and kidney function indexes,the incidence of adverse drug reactions were recorded and compared between these two groups after 12 weeks,24 weeks,and 48 weeks of TDF treatment.Results(1)There was no significantly difference in gender,average age and average length between these two groups(P>0.05)(2)The undetectable rate of HBV DNA at 12 weeks in group A was 66.66%,which was significantly higher than that of 40.90%in group B(χ^(2)=5.27,P=0.028<0.05).The undetectable rate of HBV DNA at 24 weeks and 48 weeks after TDF treatment in group A were 83.33%,and 94.44%,respectively,which were higher than those of 72.72%,and 86.36%in group B but didn’t reach significance(χ^(2)=1.27,χ^(2)=1.43;all P=0.21:P>0.05)(3)Comparison of liver function recovery rate:at 12 weeks,the recovery rate in group A was 75.00%(12/16),which was significantly higher than that of 33.33%in group B:(8/24)(χ^(2)=6.67,P=0.019<0.05).There were no significant differences between these two groups at weeks 24 and weeks 48(P>0.05)(4)Adverse reactions:there were two cases had gastrointestinal reactions such as nausea and vomiting,and one case had a slight decrease in blood phosphorus.No obvious renal damage was observed in these patients within one year.Conclusion Significant antiviral efficacy and complete virus control can be achieved by TDF treatment in a short period of time.The treatment is efficient for ETV-resistance and poor-responsive patients for controlling viral replication,and delaying the progression and evolution of the disease.