替诺福韦酯初始单药治疗慢性乙型肝炎患者5年疗效分析

Efficacy of Tenofovir Treatment for up to 5 Years in Chinese Nucleos(t)ide-Na?ve Chronic Hepatitis B Patients

【目的】分析慢性乙型肝炎患者(尤其是高病毒载量患者)服用替诺福韦酯(TDF)长达5年的治疗疗效与安全性。【方法】回顾性分析144名慢性乙型肝炎患者接受TDF初始治疗(服用TDF≥3个月)的疗效及安全性,其中HBeAg阳性106例(73.6%),HBeAg阴性38例(26.4%),102名患者基线HBV DNA(U/mL)的对数≥6。主要终点指标是获得病毒学应答率(VR);次要终点为ALT正常率(ALT水平低于正常上限)、HBeAg/HBeAb血清学转换率和安全性。【结果】平均随访时间为120(12~264)周,患者的平均年龄为34(27~41)岁。随访至24、48、96、144、192和240周时,VR率呈递增的趋势,分别为71%、91.3%、98.1%、100%、100%和100%,而且100%的患者在240周获得VR。102名基线HBV DNA(U/mL)的对数≥6的患者在随访期间均出现了VR。ALT复常率分别为72.1%、78.6%、91.2%、95%、96%和100%。第240周HBeAg率达35.8%。在第120周,1名患者发生HBsAg转阴,但没有获得HBsAg/HBsAb血清学转换。随访至24周时,有35名患者可检测到HBV DNA,即出现部分病毒学应答。这35名患者中有30名(85.7%)继续TDF单药治疗至144周时获得了VR。无一例患者出现严重不良事件。【结论】无论基线水平是否为高病毒载量,慢性乙型肝炎患长期TDF初始单药治疗是安全有效的。24周时发生部分病毒学应答继续TDF单药治疗,没有必要进行优化治疗。

【Objective】To analyze the efficacy and safety of tenofovir(TDF)treatment for up to 5 years in nucleos(t)ide-na?ve chronic hepatitis B patients,especially those with a high viral load in real life.【Methods】We retrospective-ly analyzed 144 nucleos(t)ide-na?ve chronic hepatitis B patients who received TDF monotherapy for at least 3 months,of whom 106(73.6%)were HBeAg-positive and 38(26.4%)were HBeAg-negative.102 patients had lg HBV DNA levels(U/mL)higher than 6.The primary endpoint measure was the probability of achieving a virological response(VR;unde-tectable serum HBV DNA,<100 U/mL).The secondary endpoints were ALT normalization(ALT<upper limit of nor-mal),HBeAg seroconversion,and safety.【Results】The median follow-up period was 120(12~264)weeks,and the mean patient age was 34(27~41)years.When followed up for 24,48,96,144,196,and 240 weeks,an incremental trend was observed in the rate of VR:71%,91.3%,98.1%,100%,100%and 100%,respectively.102 patients with lg HBV DNA levels(U/mL)≥6 at baseline achieved VR during the follow-up period.The ALT normalization rates were 72.1%,78.6%,91.2%,95%,96%,and 100%,respectively.The rate of HBeAg loss reached 35.8%at week 240.One patient achieved HBsAg seroclearance at 120 weeks,and did not show HBsAg/HBsAb seroconversion.HBV DNA was still detect-able(partial VR:PVR)in 35 patients at 24 weeks of follow-up,and 30 of the 35(85.7%)patients needed more than 144 weeks of continuous TDF therapy to achieve VR.No serious adverse event was reported.【Conclusions】Long-term TDF treatment of nucleos(t)ide-na?ve chronic hepatitis B patients regardless of high viral load at baseline was effective and safe in real life.Adjustment of TDF monotherapy may be unnecessary in nucleos(t)ide-na?ve patients with PVR at 24 weeks.