肾功能不全的慢性乙型肝炎患者减低剂量的替诺福韦酯富马

StephenW

Maintained virologic suppression and renal function with reduced dose tenofovir disoproxil fumarate in renally impaired chronic hepatitis B patients
Kin Seng Liem  1   2 , David K Wong  1 , Scott Fung  1 , Alireza Zahirieh  3 , Colina Yim  1 , Wayel R Zanjir  1 , Jordan J Feld  1   4 , Bettina E Hansen  1   5 , Harry L A Janssen  1
Affiliations
Affiliations

    1
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.
    2
    Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
    3
    Sunnybrook Health Sciences Centre, Toronto, Canada.
    4
    McLaughlin-Rotman Centre for Global Health, Toronto, Canada.
    5
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

    PMID: 32896948 DOI: 10.1111/jvh.13401

Abstract

Tenofovir disoproxil fumarate (TDF) effectively suppresses viral replication in chronic hepatitis B (CHB), but occasionally leads to renal impairment. We evaluated the prevalence of viral and biochemical breakthrough and renal function kinetics in renally impaired CHB patients on reduced and on full dose TDF.This clinic-based longitudinal cohort study included patients receiving full and reduced dose TDF (due to eGFR (Cockcroft-Gault) <60mL/min/1.73m2 ). Viral and biochemical breakthroughs were assessed 1 month after starting full and reduced TDF dose until the end of follow-up. Breakthroughs were studied in full and reduced dose TDF, and renal function (MDRD) longitudinally before and after dose reduction within patients starting on full dose TDF. Of 750 patients on TDF, 78 (10%) had reduced dose and 672 (90%) full dose. At the time of dose reduction, 36 (46%) patients had chronic kidney disease stage G3B. A viral breakthrough occurred in one cirrhotic dialysis-dependent patient (dosed 300 mg weekly) which resolved without signs of decompensation, and in one patient on full dose which resolved spontaneously. One biochemical breakthrough occurred during dose reduction and resolved naturally without viral breakthrough. The MDRD improved within the first year of dose reduction (+3.0 (2.5) mL/min per year; p<0.005) and remained stable thereafter. Fifty-three (79%) patients reached an MDRD >50mL/min during dose reduction.Low dose TDF maintains renal function and viral suppression in most renally impaired CHB patients, even in those with advanced liver disease. This useful, yet simple strategy could be particularly viable in resource-constrained settings.

Keywords: Chronic hepatitis B; renal impairment; tenofovir disoproxil fumarate; viral hepatitis.

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StephenW

肾功能不全的慢性乙型肝炎患者减低剂量的替诺福韦酯富马酸可维持病毒学抑制和肾功能
Kin Seng Liem 1 2，David K Wong 1，Scott Fung 1，Alireza Zahirieh 3，Colina Yim 1，Wael R Zanjir 1，Jordan J Feld 1 4，Bettina E Hansen 1 5，Harry L A Janssen 1
隶属关系
隶属关系

    1个
    加拿大多伦多大学健康网络多伦多总医院多伦多肝病中心。
    2
    荷兰鹿特丹伊拉斯姆斯大学医学中心消化内科和肝病科。
    3
    加拿大多伦多森尼布鲁克健康科学中心。
    4
    麦克劳克林-罗特曼全球卫生中心，加拿大多伦多。
    5
    加拿大多伦多大学，卫生政策，管理与评估研究所。

    PMID：32896948 DOI：10.1111 / jvh.13401

抽象

替诺福韦富马酸替索罗非酯（TDF）有效抑制慢性乙型肝炎（CHB）中的病毒复制，但偶尔会导致肾功能不全。我们评估了低剂量和全剂量TDF对肾功能不全的CHB患者的病毒和生化突破和肾功能动力学的患病率。这项基于临床的纵向队列研究包括接受全剂量和降低剂量TDF的患者（由于eGFR（Cockcroft-Gault） <60mL / min / 1.73m2）。在开始全剂量并在随访结束时减少TDF剂量后1个月，评估病毒和生化突破。在以全剂量TDF开始的患者中，在全剂量和降低剂量的TDF以及在降低剂量前后前后的肾功能（MDRD）纵向研究了突破。在750名接受TDF的患者中，有78名（10％）的剂量减少了，而有672名（90％）的全剂量。在减少剂量时，有36名（46％）患者患有慢性肾脏疾病G3B期。一名肝硬化依赖透析的患者（每周剂量300毫克）发生病毒突破，但没有出现代偿失调迹象，另一名患者全剂量自发解决。在剂量减少期间发生了一项生化突破，并且自然消除了而没有病毒突破。在降低剂量的第一年内，MDRD有所改善（每年+3.0（2.5）mL / min； p <0.005），此后保持稳定。 53名（79％）患者在减量过程中达到MDRD> 50mL / min。低剂量的TDF可以维持大多数肾功能不全的CHB患者的肾功能和病毒抑制，即使是晚期肝病患者也是如此。在资源有限的环境中，这种有用而又简单的策略可能特别可行。

关键字：慢性乙型肝炎；肾功能不全;替诺福韦富马酸替索罗非酯;病毒性肝炎。

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