长期替诺福韦治疗对核苷/核苷酸类似物耐药的慢性乙型肝炎

StephenW

Journal of Gastroenterology

May 2017, Volume 52, Issue 5, pp 641–651
Efficacy of long-term tenofovir-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs

    Authors
    Authors and affiliations

    Fumitaka SuzukiEmail authorYoshiyuki SuzukiTetsuya HosakaHitomi SezakiNorio AkutaShunichiro FujiyamaYusuke KawamuraMasahiro KobayashiSatoshi SaitohYasuji AraseKenji IkedaMariko KobayashiRie MinetaYukiko SuzukiHiromitsu Kumada

    Fumitaka Suzuki        1 2 Email author
    Yoshiyuki Suzuki        1
    Tetsuya Hosaka        1
    Hitomi Sezaki        1
    Norio Akuta        1
    Shunichiro Fujiyama        1
    Yusuke Kawamura        1
    Masahiro Kobayashi        1   
Satoshi Saitoh        1
    Yasuji Arase        1
    Kenji Ikeda        1
    Mariko Kobayashi        3
    Rie Mineta        3
    Yukiko Suzuki        3
    Hiromitsu Kumada        1

    1.Department of HepatologyToranomon HospitalTokyoJapan
    2.Okinaka Memorial Institute for Medical ResearchTokyoJapan
    3.Research Institute for HepatologyToranomon Branch HospitalKawasakiJapan

Original Article—Liver, Pancreas, and Biliary Tract

First Online:
    03 October 2016

DOI: 10.1007/s00535-016-1270-5

Cite this article as:
    Suzuki, F., Suzuki, Y., Hosaka, T. et al. J Gastroenterol (2017) 52: 641. doi:10.1007/s00535-016-1270-5

    327 Downloads

Abstract
Background

Few studies have investigated the efficacy of long-term tenofovir disoproxil fumarate (TDF)-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs.
Methods

We retrospectively analyzed 40 Japanese patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs who received TDF-based rescue therapy [TDF monotherapy, TDF plus lamivudine (LAM) combination therapy, or TDF plus entecavir (ETV) combination therapy] followed up for a median of 45 months (range 14–99 months). Viral response, changes in hepatitis B surface antigen levels from the baseline, and viral breakthrough during therapy were analyzed.
Results

The proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels (less than 2.1 log copies per milliliter) (viral response) during TDF-based rescue therapy was 68, 78, 85, 88, 83, 81, 88, and 100 % at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 years respectively. There were no differences in the viral response rate between the TDF plus LAM group and the TDF plus ETV group. The mean reduction from the baseline in hepatitis B surface antigen levels in patients with LAM-resistant HBV was greater than the reductions in patients with adefovir dipivoxil (ADV)-resistant or ETV-resistant HBV at 2 and 3 years (P = 0.024, and P = 0.025 respectively). However, two patients with ADV- or ETV-resistant HBV at the baseline developed viral breakthrough during TDF-based rescue therapy.
Conclusions

Long-term therapy with a TDF-based rescue regimen demonstrated high viral suppression in patients in whom LAM plus ADV combination therapy, ETV plus ADV combination therapy, or ETV monotherapy had failed. However, patients with ADV- or ETV-resistant HBV at the baseline may develop viral breakthrough and resistance, and careful follow-up is advised.

StephenW

胃肠病学杂志

2017年5月，第52卷，第5期，第641-651页
长期替诺福韦治疗对核苷/核苷酸类似物耐药的慢性乙型肝炎患者的疗效

    作者
    作者和附属机构

    Fumitaka铃木电子邮件作者Yoshiyuki SuzukiTetsuya HosakaHitomi SezakiNorio AkutaShunichiro藤山裕介川村马夏郎小林濑户斋藤佑彦仁川池田小林小林孝美子子子铃木希罗木齐

    铃木铃木1 2电邮作者
    铃木铃木1
    Tetsuya Hosaka 1
    Hitomi Sezaki 1
    Norio Akuta 1
    富士山一郎1
    川村佑介1
    小林正希1
Satoshi Saitoh 1
    安三治1
    池田健二1
    小林美子3
    Rie Mineta 3
    铃木铃子3
    Hiromitsu Kumada 1

    肝癌医院东京日本日本
    奥金卡纪念医学研究所东京日本
    日本川崎医学研究所

原肝，胰腺和胆道

首先在线：
    2016年10月03日

DOI：10.1007 / s00535-016-1270-5

引用本文：
    Suzuki，F.，Suzuki，Y.，Hosaka，T。等人J Gastroenterol（2017）52：641。doi：10.1007 / s00535-016-1270-5

    327下载

抽象
背景

很少有研究调查了长期替诺福韦地索普西富马酸（TDF）的救援治疗对于核苷/核苷酸类似物耐药的慢性乙型肝炎患者的疗效。
方法

我们回顾性分析了40位日本患有慢性乙型肝炎病毒的核苷/核苷酸类似物，其接受了基于TDF的救援治疗[TDF单药，TDF加拉米夫定（LAM）联合治疗或TDF加恩替卡韦（ETV）联合治疗）中位数45个月（14-99个月）。分析病毒反应，乙型肝炎表面抗原水平从基线的变化以及治疗期间的病毒突破。
结果

在基于TDF的挽救治疗期间，不可检测的血清乙型肝炎病毒（HBV）DNA水平（小于2.1log拷贝/毫升）（病毒反应）的比例为68,78,85,88,83,81,88和分别为0.5,1,1.5,2,2.5,3,3.5和4年的100％。 TDF加LAM组与TDF加ETV组病毒反应率无差异。乙型肝炎表面抗原水平的基线水平在平均水平上比LAM耐药HBV降低大于阿德福韦酯（ADV）抗性或ETV抗性HBV 2年和3年患者的减少（P = 0.024，和P = 0.025）。然而，两名基线患有ADV或ETV的HBV患者在基于TDF的抢救治疗过程中发展出病毒性突破。
结论

使用基于TDF的挽救方案进行长期治疗显示，LAM加ADV联合治疗，ETV加ADV联合治疗或ETV单一疗法失败的患者中高度病毒抑制。然而，基线患有ADV或ETV抗性HBV的患者可能会发展病毒突破和抵抗力，并建议慎重的后续行动。