将拉米夫定与阿德福韦酯联合治疗转换为恩替卡韦单药治疗

StephenW

Int J Med Sci. 2019 Jan 1;16(1):17-22. doi: 10.7150/ijms.28700. eCollection 2019.
Switching Lamivudine with Adefovir Dipivoxil Combination Therapy to Entecavir Monotherapy Provides Better Viral Suppression and Kidney Safety.
Lian JS1, Zhang XL1,2, Lu YF1, Chen JY1, Zhang YM1, Jia HY1, Zhang Z3, Yang YD1.
Author information

1
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China.
2
    Shanghai Public Health Clinical Center, Shanghai Public Health Clinical Center Affiliated to Fudan University.
3
    Urology Department, The First Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University. Hangzhou 310003, China.

Abstract

Introduction: Most chronic hepatitis B (CHB) patients in China are primitively treated with a combination of lamivudine (LAM) and adefovir dipivoxil (ADV). Although antiviral resistance can be avoided with this combination therapy, using it can have harmful side effects related to ADV, specifically kidney and bone injury. This study was designed to compare viral suppression and kidney safety when switching LAM and ADV combination therapy de novo to entecavir (ETV) monotherapy in patients with CHB and compensated hepatic cirrhosis. Materials and methods: In total, 360 CHB and compensated liver cirrhosis patients who received treatment of LAM and ADV combination therapy for more than 1 year were included in this study. One hundred and eighty patients continued combination therapy to serve as a control group and the other 180 patients were switched to ETV monotherapy to serve as the experimental group. The total course of therapy was 3 years. Laboratory studies were done every 3 months to measure liver and kidney function. Studies included glomerular filtration rate (eGFR), HBV-DNA, urine β2-microglobulin (β2-M) and retinol binding protein (RBP). Results: In the experimental group, an HBV-DNA level below 20 IU/ml was found in 77.65%, 85.88%, and 94.77% in years 1, 2, and 3, respectively. In the control group, HBV-DNA levels were below 20 IU/ml in 69.66%, 75.42%, and 85.80% in years 1, 2, and 3, respectively. Low HBV-DNA levels in the experimental group were significantly less common than in the control group on the second and third year; P values were 0.009 and 0.006 for years 2 and 3, respectively. The cumulative genetic mutation rate was 3.49% in the experimental group and 8.88% in the control group (P=0.044). Decreases in eGFR more than 30% from baseline were found in 0%, 0.56%, and 1.74% of patients in the experimental group and 4.49%, 9.14% and 14.79% in patients in the control group in the first, second, and third year, respectively. Serum creatinine more than 50 μmol/L above baseline was found in 0%, 0% and 1.74% of patients in the experimental group and 1.12%, 4.00% and 5.32% of patients in the control group in years 1, 2, and 3, respectively. The urine β2-M and RBP levels were abnormal more often in the experimental group than in the control group. Conclusion: Switching to ETV monotherapy can decrease HBV-DNA levels, reduce the genetic mutation rate, and prevent renal damage caused by LAM and ADV combination therapy in patients with CHB and compensated liver cirrhosis. Patients receiving LAM and ADV combination therapy de novo should be switched to ETV monotherapy immediately.
KEYWORDS:

ETV, LAM and ADV combination therapy de novo; kidney safety; switch

PMID:
    30662324
PMCID:
    PMC6332476
DOI:
    10.7150/ijms.28700

StephenW

Int J Med Sci。 2019年1月1日; 16（1）：17-22。 doi：10.7150 / ijms.28700。 eCollection 2019。
将拉米夫定与阿德福韦酯联合治疗转换为恩替卡韦单药治疗可提供更好的病毒抑制和肾脏安全性。
Lian JS1，Zhang XL1,2，Lu YF1，Chen JY1，Zhang YM1，Jia HY1，Zhang Z3，Yang YD1。
作者信息

1
    浙江大学医学院附属第一医院感染科，传染病诊断与治疗国家重点实验室，传染病诊疗协同创新中心。浙江杭州310003
2
    上海市公共卫生临床中心，复旦大学附属上海市公共卫生临床中心。
3
    浙江大学第一附属医院泌尿外科，浙江大学医学院。浙江杭州310003

抽象

简介：中国大多数慢性乙型肝炎（CHB）患者使用拉米夫定（LAM）和阿德福韦酯（ADV）进行原始治疗。虽然这种联合疗法可以避免抗病毒药物的抵抗，但使用它可能会产生与ADV相关的有害副作用，特别是肾脏和骨骼损伤。本研究旨在比较CHB和补偿性肝硬化患者将LAM和ADV联合治疗从头转为恩替卡韦（ETV）单药治疗时的病毒抑制和肾脏安全性。材料与方法：本研究共纳入360例CHB和代偿性肝硬化患者，这些患者接受LAM和ADV联合治疗1年以上。 180名患者继续联合治疗作为对照组，其他180名患者转为ETV单一疗法作为实验组。整个疗程为3年。每3个月进行一次实验室研究以测量肝肾功能。研究包括肾小球滤过率（eGFR），HBV-DNA，尿β2-微球蛋白（β2-M）和视黄醇结合蛋白（RBP）。结果：在实验组中，在第1,2和3年，HBV-DNA水平低于20 IU / ml，分别为77.65％，85.88％和94.77％。在对照组中，HBV-DNA水平低于20IU / ml，分别在第1,2和3年分别为69.66％，75.42％和85.80％。实验组低HBV-DNA水平在第2年和第3年显着低于对照组;对于第2年和第3年，P值分别为0.009和0.006。实验组累积基因突变率为3.49％，对照组为8.88％（P = 0.044）。实验组患者的eGFR从基线降低超过30％，对照组患者在第一，第二和第三位患者中分别为4.49％，9.14％和14.79％。一年，分别。实验组患者中0％，0％和1.74％的患者血清肌酐高于基线50μmol/ L，对照组患者在1年级，2年级和3年时分别为1.12％，4.00％和5.32％。 ， 分别。实验组尿β2-M和RBP水平异常多于对照组。结论：转为ETV单药治疗可降低CHB和补偿性肝硬化患者的HBV-DNA水平，降低基因突变率，预防LAM和ADV联合治疗引起的肾损害。接受LAM和ADV联合治疗的患者应立即转为ETV单药治疗。
关键词：

ETV，LAM和ADV联合治疗从头开始;肾安全;开关

结论：
    30662324
PMCID：
    PMC6332476
DOI：
    10.7150 / ijms.28700

StephenW

http://www.medsci.org/v16p0017.htm