Shin Jung-Ho, Kwon Hee Jin, Jang Hye Ryoun, Lee Jung Eun, Gwak Geum-Youn, Huh Wooseong, Jung Sin-Ho, Lee Joon Hyeok, Kim Yoon-Goo, Kim Dae Joong, Oh Ha Young
From the Department of Medicine, Division of Nephrology (JHS, HJK, HRJ, JEL, WH, YGK, DJK, HYO); Department of Medicine, Division of Gastroenterology and Hepatology (GYG, JHL); and Biostatistics and Clinical Epidemiology Center (SHJ), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Medicine (Baltimore). 2016 Jan;95(1):e2400. doi: 10.1097/MD.0000000000002400.
Renal functional decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects on overall prognosis. It, however, is difficult to distinguish vulnerable patients who may experience renal dysfunction because most previous CHB studies were conducted in relatively healthy individuals. In this retrospective observational study, renal functional decline in CHB patients receiving oral antiviral agents for more than 6 months was analyzed and risk factors of chronic kidney disease (CKD) progression were determined. Renal functional decline was defined when the estimated glomerular filtration rate (eGFR) decreased by more than 25% from baseline and rapid CKD progression was defined as eGFR decreased by more than 5 mL/min/1.73 m2/y among patients who experienced renal functional decline. A total of 4178 patients were followed up for a median 23 months. Antiviral agents included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal functional decline occurred in 706 (16.9%) patients. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics increased the hazard ratio for renal functional decline; however, clevudine reduced risk. The eGFR significantly increased over time in patients receiving telbivudine or clevudine compared with lamivudine. Among the 3175 patients followed up for more than 1 year, 407 (12.8%) patients experienced rapid CKD progression. Patients with rapid CKD progression showed lower serum albumin, higher total bilirubin, and prolonged prothrombin time compared with patients with stable renal function, but hepatitis B envelope antigen positivity and hepatitis B virus deoxyribonucleic acid level did not differ between the control and rapid CKD progression groups. Age, diabetes, kidney transplantation, underlying CKD, and simultaneous administration of diuretics were identified as risk factors for rapid CKD progression, and clevudine showed a beneficial effect. Age, hypertension, diabetes, liver or kidney transplantation, underlying CKD, and diuretics were identified as risk factors for renal functional decline. This study suggests that close monitoring of renal function and adequate management are required for CHB patients receiving antiviral agents with these risk factors.
慢性乙型肝炎（CHB）治疗期间常见的肾功能下降会对整体预后产生不利影响。然而，由于大多数既往CHB研究是在相对健康的个体中进行的，因此很难区分可能出现肾功能障碍的易感患者。在这项回顾性观察研究中，分析了接受口服抗病毒药物治疗6个月以上的CHB患者的肾功能下降情况，并确定了慢性肾脏病（CKD）进展的危险因素。当估计肾小球滤过率（eGFR）较基线下降超过25%时定义为肾功能下降，在出现肾功能下降的患者中，eGFR下降超过5 mL/min/1.73 m2/y定义为CKD快速进展。共对4178例患者进行了中位23个月的随访。抗病毒药物包括拉米夫定（17.0%）、阿德福韦（3.7%）、恩替卡韦（70.4%）、替比夫定（0.6%）、替诺福韦（4.0%）或克拉夫定（4.3%）。706例（16.9%）患者出现肾功能下降。基于多变量Cox回归分析，年龄、高血压、糖尿病、肝或肾移植史、潜在的CKD以及同时使用利尿剂会增加肾功能下降的风险比；然而，克拉夫定可降低风险。与拉米夫定相比，接受替比夫定或克拉夫定治疗的患者eGFR随时间显著升高。在随访超过1年的3175例患者中，407例（12.8%）患者出现CKD快速进展。与肾功能稳定的患者相比，CKD快速进展的患者血清白蛋白较低、总胆红素较高且凝血酶原时间延长，但对照组和CKD快速进展组之间乙肝e抗原阳性率和乙肝病毒脱氧核糖核酸水平无差异。年龄、糖尿病、肾移植、潜在的CKD以及同时使用利尿剂被确定为CKD快速进展的危险因素，克拉夫定显示出有益作用。年龄、高血压、糖尿病、肝或肾移植、潜在的CKD以及利尿剂被确定为肾功能下降的危险因素。这项研究表明，对于具有这些危险因素且接受抗病毒药物治疗的CHB患者，需要密切监测肾功能并进行适当管理。
