EASL 2018 FRI-345 持续的病毒学抑制和改善的肾功能 肾功能减退

StephenW

EASL 2018 FRI-345
Sustained virological suppression and improved renal function
with reduced dose tenofovir disoproxil fumarate in renally
compromised patients with chronic hepatitis B
S. Liem1,2, D.Wong1, S. Fung1, A. Zahirieh3, C. Yim1, H.A Shah1, J. Feld1,4,
B. Hansen1,2,5, H. Janssen1. 1University Health Network, Toronto Centre
for Liver Disease, Toronto, Canada; 2Erasmus University Medical Center
Rotterdam, Department of Gastroenterology and Hepatology, Rotterdam,
Netherlands; 3Sunnybrook Health Sciences Centre, Toronto, Canada;
4University of Toronto, McLaughlin-Rotman Centre for Global Health,
Toronto, Canada; 5University of Toronto, Institute of Health Policy,
Management and Evaluation, Toronto, Canada
Email: [email protected]
Background and Aims: Tenofovir disoproxil fumarate (TDF) therapy
effectively suppresses viral replication in patients with chronic
hepatitis B (CHB), but occasionally leads to renal impairment. We
studied prevalence of viral breakthrough (VBT) and renal function in
renally impaired CHB patients on reduced dose TDF, and in patients
on full dose TDF.
Method: CHB patients with full and reduced dose TDF (due to
eGFR (Cockcroft-Gault) <50 ml/min/1.73 m2 ± serum phosphate
<0.8 mmol/l) were identified at Toronto Centre for Liver Disease.
VBT (confirmed HBV DNA > 1logIU/ml above nadir on-therapy
(AASLD)), and biochemical breakthrough (confirmed ALT > 1.5xULN)
were assessed from 1 month after start of (reduced) TDF dose
(baseline) until end of follow-up (EOF). Renal function was assessed
by Modification of Diet in Renal Disease (MDRD) and categorized into
chronic kidney disease stages 1–5. Outcome was compared between
full and reduced dose TDF, and between before and after dose
reduction within patients who started on full dose TDF.
Results: Out of 750 patients on TDF, 78 (10%) had reduced dose vs.
672 (90%) full dose. At baseline the mean (SD) age was 69 (10) vs. 45
(13) years, 69% vs.70% was male, mean duration on TDF was 3.4 (2.4)
vs. 4.7 (3.1) years for reduced vs. full dose of TDF. Of patients on
reduced TDF dose 71% had undetectable HBV DNA (mean 1.4logIU/
ml), 82% received TDF 300mg Q48hr (range 75 mg – 300 mg Q48hr),
mean MDRD was 52 (19) ml, 42% had chronic kidney disease stage
G3b or higher and 12% had decompensated cirrhosis. Mean follow-up
was 2.6 (2.3) years. VBT occurred in 1 cirrhotic patient on dialysis
using TDF 300 mg weekly (HBV DNA peak 3.6 log) that resolved 4
months after dose increase to biweekly without signs of decompensation,
and in 1 patient on full dose TDF (resolved spontaneously).
Viral blips (HBVDNA between 1 and 2 logs on 1 occasion) occurred in
2.6% before vs. 5.4% after dose reduction (p = 0.53), and in 2.8% of
patients on continuous full dose TDF. One biochemical breakthrough
occurred in a reduced dose patient (ALT peak 2xULN) and resolved
spontaneously without VBT. During dose reduction the MDRD
increased from baseline to EOF (+6.0 (21) ml; p = 0.04) and 50 (64%)
patients reached eGFR > 50ml.
Conclusion: In CHB renal dose adjustment of TDF did not lead to
significant VBT while renal function improved. This implies that renal
dosing of TDF in CHB is effective and safe, and should be considered a
viable option in renally compromised patients.

StephenW

EASL 2018 FRI-345
持续的病毒学抑制和改善的肾功能
肾功能减退的替诺福韦二吡呋酯富马酸盐
危及慢性乙型肝炎患者
S.Liem1,2，D.Wong1，S.Fung1，A.Zahirieh3，C.Yim1，H.A Shah1，J.Feld1,4，
B. Hansen1,2,5，H.Janssen1。 1大学健康网络，多伦多中心
肝病，加拿大多伦多; 2伊拉斯姆斯大学医学中心
鹿特丹，胃肠病学和肝病学系，鹿特丹，
荷兰;加拿大多伦多3Sunnybrook健康科学中心;
4多伦多大学McLaughlin-Rotman全球卫生中心，
加拿大多伦多; 5多伦多大学卫生政策研究所，
管理和评估，加拿大多伦多
电子邮件：[email protected]
背景和目的：替诺福韦酯替诺福韦（TDF）治疗
有效抑制慢性乙型肝炎患者的病毒复制
乙型肝炎（CHB），但偶尔会导致肾脏损害。我们
研究了病毒突破（VBT）和肾功能的流行
肾功能减退的慢性肾功能衰竭患者和患者
在全剂量TDF。
方法：慢性充血性和减量剂量的慢性乙型肝炎患者（由于
eGFR（Cockcroft-Gault）<50ml / min / 1.73m 2±血清磷酸盐
<0.8 mmol / l）在多伦多肝病中心发现。
VBT（证实HBV DNA> 1logIU / ml，高于最低点治疗
（AASLD））和生化突破（确诊ALT> 1.5xULN）
从（减少的）TDF剂量开始后1个月开始评估
（基线）直到随访结束（EOF）。评估肾功能
通过改变饮食在肾脏疾病（MDRD）并且被分类入
慢性肾病阶段1-5。比较结果
全剂量和减量剂量TDF，以及剂量之前和之后
减少开始全剂量TDF的患者。
结果：在TDF的750名患者中，78名（10％）剂量减少vs.
672（90％）全剂量。在基线时，平均（SD）年龄为69（10）比45
（13）岁，69％vs.70％为男性，TDF的平均持续时间为3.4（2.4）
相比于全剂量TDF减少4.7（3.1）年。患者上
TDF剂量减少71％，HBV DNA检测不到（平均1.4logIU /
ml），82％接受TDF 300mg Q48hr（范围75mg-300mg Q48hr），
平均MDRD为52（19）ml，42％有慢性肾病分期
G3b或更高，12％有失代偿性肝硬化。平均随访
是2.6（2.3）年。 VBT发生于1例肝硬化透析患者
每周使用TDF 300 mg（HBV DNA峰值3.6 log），解决4
给药后两个月增加至两周没有代偿失调的迹象，
和1例全剂量TDF患者（自发缓解）。
发生病毒性红斑（HBVDNA 1次发生1次，2次发生）
剂量减少后2.6％前后比5.4％（p = 0.53），2.8％
连续全剂量TDF患者。一个生化突破
发生在减量患者（ALT峰值2xULN）并解决
自发没有VBT。在剂量减少期间，MDRD
从基线增加到EOF（+ 6.0（21）ml; p = 0.04）和50（64％）
患者达到eGFR> 50ml。
结论：在CHB肾脏剂量调整TDF没有导致
显着VBT而肾功能改善。这意味着肾脏
在CHB中给药TDF是有效和安全的，应该被认为是a
在肾功能受损患者中可行的选择。