AASLD2019[481]富马酸替诺福尔阿拉贝酰胺有效且 第2阶段主要有

StephenW

481
TENOFOVIR ALAFENAMIDE FUMARATE IS EFFECTIVE AND
HAS SUPERIOR RENAL SAFETY MAINLY AMONG STAGE 2
CHRONIC KIDNEY DISEASE (CKD): REAL-WORLD STUDY FROM
THE CANADIAN HEPATITIS B NETWORK (CANHEPB)
Mina S. Farag1,2, Scott K Fung1, Edward Tam3, Karen E.
Doucette4, Alexander Wong5, Alnoor Ramji6, Brian Conway7,
Curtis Cooper8, Keith Tsoi9, Carla S. Coffin10, Bettina E.
Hansen1,11 and Harry L. A. Janssen1, (1)Toronto Centre for
Liver Disease, Toronto General Hospital, University Health
Network, (2)Institute of Medical Science, University of
Toronto, (3)Lair Centre, (4)Division of Infectious Diseases,
University of Alberta, (5)Department of Medicine, University
of Saskatchewan, (6)Medicine, University of British Columbia,
(7)Vancouver Infectious Diseases Centre, (8)University of
Ottawa, (9)Department of Medicine, Mcmaster University,
(10)Medicine, University of Calgary, (11)Institute of Health
Policy, Management and Evaluation, University of Toronto
Background: Tenofovir alafenamide fumarate (TAF), a new
prodrug of tenofovir has high plasma stability and results in
fewer renal adverse events compared to tenofovir disoproxil
fumarate (TDF) for chronic hepatitis B (CHB) treatment. We
aimed to study the effectiveness and renal safety of TAF
therapy in a real-world setting among CHB patients in Canada
Methods: CHB patients from 9 academic institutions across
Canadawho received TAF(either Nucleot(s)ide Analogue
(NA) naïve or experienced) were studied as part of the
Canadian Hepatitis (CanHepB) B Network. Kidney function
was measured by serum creatinine, estimated glomerular
filtration rate (eGFR) as per Cockcroft-Gault.Patients were
categorized according to theirchronic kidney disease (CKD)
stages using eGFR before switching to TAF and were followed
for 104 weeks after initiation of TAF Serum phosphate and
other biochemical and virologic markers were also serially
assessed Results: Of 103 patients receiving TAF, 81 (79%)
switched from TDF, 3 (3%) switched from another NA and 14
(14%) were NA naïve. At start of TAF treatment (baseline), the
mean (SD) age was 52 (13) years, 71 (69%) patients were
male and 81% of patients were Asian. Majority had HBV DNA
< 20 IU/mL (70%), 28 (33%) were HBeAg positive and mean
eGFR was 72.6 (0.28). CKD stages at baseline were Stage
1: 25(24%), Stage 2: 37(38%), Stage 3a: 20 (20%), Stage 3b
or higher: 17 (16%). Among the NA switch group, HBV-DNA
and HBsAg significantly declined after starting TAF (HBVDNA
log10 IU/ml during TAF:-0.07 [-0.09 - -0.06] per month;
P<0.001 vs. pre-TAF: (+0.01 [ -0.04 – 0.05]; P=0.8) (HBsAg
log10IU/ml during TAF -0.01 [-0.01 - -0.002]; P=0.009 vs. pre-
TAF: +0.11 [0.02 – 0.2]; P=0.02). eGFR increased significantly
after switching to TAF (during TAF: +0.11 [0.01- 0.22] per
month; P=0.04 vs. pre-TAF: -0.19 [95 CI% -0.35 – 0.02] per
month; P=0.02; Figure). This trend continued after the first
year of follow-up (eGFR week 0: 74.2, Week 52: 75.7, Week
104: 77.1; P<0.001). Serum phosphate decreased before
switching (-0.008 [-0.02 – -0.0004]mmol/Lper week; P=0.03)
and increased following TAF (+0.004 [0.01 – 0.12] mmol/Lper
week; P=0.03). Among patients with stage 2 CKD (eGFR 89-
60), eGFR significantly increased after switching compared
to pre-TAF (+0.20 [0.01- 0.41] per month; P=0.05 vs.-0.51
[-0.89 - -0.14] per month, P=0.01, respectively). Patients
with abnormal ALT before TAF showed a significant decline
after switching (-1.02 [-1.03 – -1.01] ULN per month; P<0.01).
Conclusion: In CHB patients on NA treatment, switching
to TAF led to improvement in kidney function, particularly in
those with stage 2 CKD. TAF was safe, well tolerated and
effective in this real-world cohort.

StephenW

481
富马酸替诺福尔阿拉贝酰胺有效且
第2阶段主要有肾脏安全
慢性肾脏病（CKD）：来自世界各地的真实研究
加拿大乙肝网络（CANHEPB）
Mina S.Farag1,2，Scott K Fung1，Edward Tam3，Karen E.
Doucette4，Alexander Wong5，Alnoor Ramji6，Brian Conway7，
柯蒂斯·库珀（Curtis Cooper）8，基思（Keith Tsoi）9，卡拉·科芬（Carla S.
Hansen1,11和Harry L.A.Janssen1，（1）多伦多中心
多伦多大学综合医院多伦多总医院肝病
网络，（2）医科大学医学研究所
多伦多（3）中心，（4）传染病科，
艾伯塔大学（5）大学医学系
萨斯喀彻温省（6）医学，不列颠哥伦比亚大学，
（7）温哥华传染病中心，（8）University of
渥太华（9）麦克马斯特大学医学系，
（10）卡尔加里大学医学（11）卫生研究所
多伦多大学政策，管理与评估
背景：新的替诺福韦阿拉芬酰胺富马酸酯（TAF）
替诺福韦的前药具有很高的血浆稳定性，并导致
与替诺福韦酯相比，肾毒性事件更少
富马酸酯（TDF）用于慢性乙型肝炎（CHB）治疗。我们
旨在研究TAF的有效性和肾脏安全性
在加拿大的CHB患者中进行现实世界的治疗
方法：来自9个学术机构的CHB患者
收到TAF（或类似核苷）的加拿大
（NA）天真或有经验）作为
加拿大乙型肝炎（CanHepB）网络。肾功能
用血清肌酐测定，估计肾小球
根据Cockcroft-Gault的滤过率（eGFR）。
根据慢性肾脏病（CKD）分类
在切换到TAF之前使用eGFR的阶段
开始TAF后持续104周
其他生化和病毒学标志物也被串行
评估结果：103名接受TAF的患者中，有81名（79％）
从TDF切换，3（3％）从另一个NA和14切换
（14％）天真。在开始TAF治疗（基线）时，
平均（SD）年龄为52（13）岁，有71（69％）名患者
男性和81％的患者为亚洲人。多数患有HBV DNA
<20 IU / mL（70％），28（33％）的HBeAg阳性且平均
eGFR为72.6（0.28）。基线的CKD阶段为Stage
1：25（24％），阶段2：37（38％），阶段3a：20（20％），阶段3b
或更高：17（16％）。在NA开关组中，HBV-DNA
开始TAF后HBsAg明显下降（HBVDNA
TAF期间log10 IU / ml：-0.07 [-0.09--0.06]每月；
P <0.001 vs. TAF前：（+ 0.01 [-0.04 – 0.05]； P = 0.8）（HBsAg
TAF期间log10IU / ml ：( -0.01 [-0.01--0.002]； P = 0.009相对于pre-
TAF：+0.11 [0.02 – 0.2]； P ＝ 0.02）。 eGFR显着增加
切换为TAF后（在TAF期间：每+0.11 [0.01- 0.22]
月; P = 0.04 vs. TAF之前：-0.19 [95 CI％-0.35 – 0.02]
月; P = 0.02；数字）。这种趋势在第一次
随访年（eGFR第0周：74.2，第52周：75.7，第周
104：77.1; P ＜0.001）。之前血清磷酸盐下降
转换（-0.008 [-0.02 – -0.0004] mmol / L每周； P = 0.03）
并在TAF后升高（+0.004 [0.01 – 0.12] mmol / Lper
周; P = 0.03）。在患有2期CKD的患者中（eGFR 89-
60），与切换后相比，eGFR显着增加
到TAF之前（每月+0.20 [0.01- 0.41]； P = 0.05与-0.51
每月[-0.89--0.14]，分别为P = 0.01）。耐心
在TAF之前出现ALT异常的患者显着下降
切换后（每月ULN [-1.02 [-1.03 – -1.01] ULN； P <0.01）。
结论：在接受NA治疗的CHB患者中，转用
TAF导致肾功能改善，尤其是
CKD 2期患者。 TAF安全，耐受性好且
在这个现实世界中有效。