替比夫定改善患者的慢性乙型肝炎肾功能

StephenW

Telbivudine Improves Renal Function in Patients With Chronic Hepatitis B

    Edward J. Ganeemail address
    ,
    Gilbert Deray
    ,
    Yun-Fan Liaw
    ,
    Seng Gee Lim
    ,
    Ching-Lung Lai
    ,
    Jens Rasenack
    ,
    Yuming Wang
    ,
    George Papatheodoridis
    ,
    Adrian Di Bisceglie
    ,
    Maria Buti
    ,
    Didier Samuel
    ,
    Alkaz Uddin
    ,
    Sophie Bosset
    ,
    Aldo Trylesinski

Received 31 May 2013; accepted 14 September 2013. published online 24 September 2013.

   
Background & Aims

There is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of telbivudine treatment of patients with chronic hepatitis B virus infection.
Methods

We used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4−6 years), as well as in patients with decompensated cirrhosis (2 years).
Results

eGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4−6 years. Increased eGFR with telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60−89 mL/min/1.73 m2 (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5−6). In decompensated patients with high renal risk, eGFR was also improved on telbivudine (+2.0%).
Conclusions

In global trials of patients with compensated and decompensated cirrhosis, long-term telbivudine therapy was associated with a sustained improvement of renal function—particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined.

StephenW

背景及宗旨

有慢性乙肝病毒感染和慢性肾脏疾病之间的密切关系。我们分析在慢性乙肝病毒感染替比夫定治疗多采用研究肾小球滤过率（GFR ）的不同的标记肾功能的变化。
方法

我们用血清肌酐为基础的方程（即克罗夫特，高尔特，饮食修正肾脏疾病，以及慢性肾脏病流行病学协作）来估计肾小球滤过率（ eGFR）为成人慢性乙肝病毒感染和代偿性肝病谁参加了第三阶段， 2年（ GLOBE研究）和长期延伸研究比较替比夫定（ 600毫克/ d）和拉米夫定（ 100毫克/天）的疗效和安全性（ 4-6年的随机，双盲研究） ，以及患者的失代偿性肝硬化（2年） 。
结果

使用克罗夫特，高尔特，饮食修正肾脏疾病，以及慢性肾脏病流行病学协作方程是一致，说明2年GLOBE研究中改善肾功能的替比夫定治疗的患者（有一个在平均增长8.5 ％计算eGFRs表皮生长因子受体的基础上，饮食在肾脏病方程的修改） 。改善肾功能维持4-6年。增加表皮生长因子受体与替比夫定治疗中也观察到风险的患者肾功能损害增加：患者有60-89 mL/min/1.73平方米（ +17.2 ％ ） ，年龄大于50岁（ 11.4％ ）基线eGFRs ，并与肝肝纤维化/肝硬化（患者·伊沙克纤维化评分在5-6 +7.2 ％ ） 。在失代偿期患者肾高风险，表皮生长因子受体也得到了改善对替比夫定（ +2.0 ％ ） 。
结论

患者的代偿和失代偿期肝硬化的全球临床试验，长期替比夫定治疗与肾功能，尤其是肾功能不全患者的危险性增加持续改善有关。这个肾脏保护作用的机制仍有待确定。