Tsai M-C, Chen C-H, Tseng P-L, Hung C-H, Chiu K-W, Wang J-H, Lu S-N, Lee C-M, Chang K-C, Yen Y-H, Lin M-T, Chou Y-P, Hu T-H
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Centre, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan.
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Centre, Taiwan.
Clin Microbiol Infect. 2016 Jan;22(1):95.e1-95.e7. doi: 10.1016/j.cmi.2015.05.035. Epub 2015 Jun 5.
This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.
本研究旨在评估富马酸替诺福韦二吡呋酯（替诺福韦）、替比夫定和恩替卡韦的肾毒性及疗效。对587例接受替诺福韦（n = 170）、替比夫定（n = 184）和恩替卡韦（n = 233）治疗至少1年的慢性乙型肝炎患者进行回顾性研究。评估肾功能和疗效。替诺福韦组在平均治疗17个月后，估计肾小球滤过率（eGFR）显著下降（从92.2降至85.6 mL/min/1.73 m²，p < 0.001），但替比夫定组在平均治疗32个月后eGFR升高（从86.1升至95 mL/min/1.73 m²，p < 0.001）。恩替卡韦组在平均治疗44个月后eGFR无显著变化。多因素分析显示，既往存在肾功能不全（p = 0.003）、替诺福韦治疗（p = 0.007）和利尿剂治疗（p = 0.001）是肾功能恶化的独立预测因素。替诺福韦治疗2年后累积病毒学突破率为0%，恩替卡韦治疗7年后为3.4%，替比夫定治疗5年后为22.9%。肝硬化（p = 0.008）和病毒学突破（p = 0.040）与肝细胞癌发生风险增加独立相关。通过连续eGFR测量评估，替诺福韦可能导致肾功能恶化。虽然替比夫定似乎与eGFR改善有关，但它与高病毒学突破率相关，而病毒学突破是肝细胞癌发生的独立危险因素。恩替卡韦病毒学突破率低且肾功能得以保留，可以成为这三种药物中的最佳选择。
