AASLD2018[434]低剂量替诺福韦Disoproxil富马酸盐 改善肾脏功能和

StephenW

434
Low Dose Tenofovir Disoproxil Fumarate
Improves Kidney Function and Sustains
Virologic Suppression in Renally Compromised
Chronic Hepatitis B Patients
Kin Seng Liem1,2, Scott K. Fung3, David KH Wong1, Alirezah
Zahirieh4, Hemant A. Shah1, Colina K. Yim1, Jordan J. Feld1,5,
Bettina E. Hansen1,2,6 and Harry L. A. Janssen1, (1)Toronto
Centre for Liver Disease, University Health Network, (2)
Dept. of Gastroenterology & Hepatology, Erasmus University
Medical Center Rotterdam, (3)University of Toronto, Toronto,
on, Canada, (4)Sunnybrook Health Sciences Center, (5)
Mclaughlin-Rotman Centre for Global Health, (6)Institute of
Health Policy, Management, and Evaluation, University of
Toronto
Background: Tenofovir disoproxil fumarate (TDF) therapy
effectively inhibits viral replication in patients with chronic
hepatitis B (CHB), but renal impairment can occur. Viral
breakthrough and renal function were studied in renally
impaired patients on reduced dose TDF and in patients on
full dose TDF. Methods: CHB patients with full and reduced
dose TDF (due to GFR [Cockcroft-Gault] <50mL/min/1.73m2
± serum phosphate <0.8mmol/L) from a North-American
hospital were evaluated. Viral breakthrough (confirmed
HBV DNA>1 log IU/mL above nadir on-therapy [AASLD])
and biochemical breakthrough (confirmed ALT>1.5x ULN)
were assessed from 1 month after starting (reduced) TDF
dose (baseline) till end of follow-up (EOF). Renal function
was calculated by Chronic Kidney Disease (CKD)-EPI and
grouped as CKD stage 1-5. Outcome was compared between
full and reduced dose TDF, and between before and after
dose reduction among patients who started on full dose
TDF. Results: Of 739 patients on TDF, 67 (9%) had reduced
dose vs. 672 (91%) full dose. At baseline the mean (SD) age
was 68 (11) vs. 45 (13) years, 63% vs.70% was male, mean
duration on TDF was 3 (2) vs. 5 (3) years for reduced vs. full
dose of TDF. Low dose patients had a baseline HBV DNA of
1.4 log (71% undetectable), 75% received TDF 300mg Q48hr
(range 75mg - 300mg Q48hr), mean CKD-EPI was 50 (20)
mL, 22% had hypophosphatemia, 46% had CKD stage G3b
or worse and 14% had decompensated cirrhosis. During a
mean follow-up of 3 (2) years, all patients continued to have
viral suppression except for 1 dialysis patient on TDF 300mg/
week who had a viral breakthrough (HBV DNA peak 3.6 log)
that resolved 4 months after dose increase to Q72hr without
decompensation and 1 patient on full dose TDF (resolved
naturally). Another reduced dose patient had a transient
ALT increase (peak 2x ULN) without rise in HBV DNA. The
CKD-EPI decline observed during full dose TDF reversed in
the first year of lower dosing and remained stable thereafter
(+2.0 (13) mL at EOF vs. baseline; p=0.28), with 50 (75%)
patients reaching CKD-EPI>50mL and 11/15 (73%) patients
normalizing serum phosphate. None developed Fanconi
syndrome or lactic acidosis. TDF was further dose reduced or
switched to ETV/LAM in 11% of patients and dose increased
due to improved GFR in 14%. Conclusion: Low dose TDF
could preserve renal function and sustain viral suppression in
most renally impaired CHB patients, even with advanced liver
disease. This useful, yet simple strategy could be especially
feasible in resource limited settings.

StephenW

434
低剂量替诺福韦Disoproxil富马酸盐
改善肾脏功能和维持
真正受损的病毒学抑制
慢性乙型肝炎患者
Kin Seng Liem1,2，Scott K. Fung3，David KH Wong1，Alirezah
Zahirieh4，Hemant A. Shah1，Colina K. Yim1，Jordan J. Feld1,5，
Bettina E. Hansen1,2,6和Harry L. A. Janssen1，（1）多伦多
大学卫生网络肝病中心，（2）
伊拉斯姆斯大学消化内科和肝病学系
鹿特丹医疗中心，（3）多伦多大学，多伦多，
on，Canada，（4）Sunnybrook健康科学中心，（5）
Mclaughlin-Rotman全球卫生中心，（6）全球卫生研究所
大学卫生政策，管理和评估
多伦多
背景：替诺福韦地索普西富马酸盐（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），但可发生肾功能损害。病毒
在肾脏方面研究突破和肾功能
减少剂量TDF和患者的受损患者
全剂量TDF。方法：CHB患者充分和减少
剂量TDF（由于GFR [Cockcroft-Gault] <50mL / min / 1.73m2
来自北美的血清磷酸盐<0.8mmol / L）
医院进行了评估。病毒突破（证实
HBV DNA> 1 log IU / mL高于最低点治疗[AASLD]）
和生化突破（确认ALT> 1.5x ULN）
在开始（减少）TDF后1个月评估
剂量（基线）直至随访结束（EOF）。肾功能
由慢性肾病（CKD）-EPI和
分为CKD阶段1-5。结果进行了比较
完全和减少剂量TDF，以及之前和之后
开始全剂量的患者的剂量减少
TDF。结果：在739例TDF患者中，67例（9％）减少
剂量与672（91％）全剂量。在基线时平均（SD）年龄
是68（11）对45（13）年，63％对70％是男性，意思是
TDF持续时间为3（2），而减少与完全持续时间为5（3）年
剂量的TDF。低剂量患者的基线HBV DNA为
1.4 log（71％检测不到），75％收到TDF 300mg Q48hr
（范围75mg-300mg Q48hr），平均CKD-EPI为50（20）
mL，22％患有低磷血症，46％患有CKD期G3b
或更糟，14％的人失代偿性肝硬化。期间
平均随访3（2）年，所有患者继续有
病毒抑制除1名透析患者外，TDF 300mg /
有病毒突破的一周（HBV DNA峰值3.6 log）
剂量增加至Q72hr后4个月消退
失代偿和1名全剂量TDF患者（已解决
自然）。另一个减剂患者有一个短暂的
ALT增加（峰值2x ULN）而HBV DNA没有升高。该
在全剂量TDF逆转期间观察到CKD-EPI下降
较低剂量的第一年，此后保持稳定
（EOF与基线相比，+ 2.0（13）mL; p = 0.28），50（75％）
患者达到CKD-EPI> 50mL和11/15（73％）患者
血清磷酸正常化。没有开发Fanconi
综合征或乳酸性酸中毒。 TDF进一步减少剂量或
11％的患者转为ETV / LAM，剂量增加
由于GFR提高了14％。结论：低剂量TDF
能维持肾功能，维持病毒抑制
大多数肾功能受损的CHB患者，即使是晚期肝脏
疾病。这个有用但简单的策略可能尤其如此
资源有限的设置是可行的。