替诺福韦与恩替卡韦再治疗对α-干扰素治疗不应答的慢性乙型肝炎患者疗效比较研究

Re-treatment of chronic hepatitis B non-responders to pegylated interferon-αby tenofovir and entecavir

目的比较替诺福韦与恩替卡韦再治疗对α-干扰素治疗不应答的慢性乙型肝炎(CHB)患者的疗效。方法2016年6月~2020年3月我院诊治的CHB患者77例,均为接受过聚乙二醇α-干扰素治疗6个月后不应答的患者,其中接受替诺福韦治疗者41例,接受恩替卡韦治疗者36例。采用实时荧光定量PCR法检测血清HBV DNA载量,采用ELISA法检测血清HBsAg和HBeAg,使用CytoFLEX型流式细胞仪检测外周血CD4^(+)和CD8^(+)T淋巴细胞亚群。结果在治疗6个月和12个月末,替诺福韦治疗组血清ALT复常率分别为80.5%和90.2%,与恩替卡韦治疗组的77.8%和86.1%比,差异均无统计学意义(P>0.05),血清HBV DNA转阴率分别为65.9%和95.1%,与恩替卡韦治疗组的63.9%和88.9%比,差异也无统计学意义(P>0.05);替诺福韦治疗组外周血CD4^(+)细胞百分比分别为(33.9±3.9)%和(38.6±5.6)%,显著高于恩替卡韦治疗的【(30.2±3.7)%和(35.1±3.6)%,P<0.05】,CD4^(+)/CD8^(+)细胞比值分别为(1.2±0.1)和(1.5±0.1),显著高于恩替卡韦治疗组[(1.0±0.0)和(1.3±0.1),P<0.05];在12个月的观察期内,替诺福韦治疗组耐药发生率为4.9%,与恩替卡韦治疗组的2.8%比,差异无统计学意义(x^(2)=0.013,P=0.908)。结论替诺福韦与恩替卡韦治疗对聚乙二醇α-干扰素治疗不应答的CHB患者均可获得很好的疗效,但替诺福韦在提高免疫功能方面优于恩替卡韦治疗,延长疗程观察是否能提高血清HBeAg转阴率值得研究。

Objective The aim of this study was to compare the efficacy of re-treatment of chronic hepatitis B(CHB)non-responders to pegylated interferon-αby tenofovir and entecavir.Methods 77 patients with CHB who were the non-responders to pegylated interferon-αwere recruited in our hospital between June 2016 and March 2020,and divided into two groups,receiving tenofovir(n=41)or entecavir(n=36),respectively.Serum HBV DNA and HBsAg and HBeAg were assayed routinely,and peripheral blood lymphocyte subsets was detected by FCM.Results At the end of six and twelve month treatment,serum alanineaminotransferase normalization rates in tenofovir-treated patients were 80.5%and 90.2%,not significantly different as compared to 77.8%and 86.1%in entecavir-treated patients(P>0.05),serum HBV DNA loss were 65.9%and 95.1%,also not significantly different as compared to 63.9%and 88.9%(P>0.05)in entecavir-treated patients;the percentage of peripheral blood CD4^(+)cells in tenofovir-treated patients were(33.9±3.9)%and(38.6±5.6)%,significantly higher than[(30.2±3.7)%and(35.1±3.6)%,respectively,P<0.05],and the CD4^(+)/CD8^(+)cell ratio were(1.2±0.1)and(1.5±0.1),significantly higher than[(1.0±0.0)and(1.3±0.1),respectively,P<0.05]in entecavir-treated patients;during the 12-month observation period,the resistance rate in tenofovir-treated patients was 4.9%,not significantly different compared to 2.8%in entecavirtreated patients(x^(2)=0.013,P=0.908).Conclusion The administration of tenofovir and entecavir in the treatment of CHB patients who do not respond to polyethylene glycol interferon-αcould obtain a good clinical efficacy,while the tenofovir could improve immune functions,which might improve serological response and warrants further investigation.