Faculty of Medicine Siriraj Hospital, Division of Gastroenterology, Department of Medicine, Mahidol University, Bangkok, Thailand.
Faculty of Medicine Siriraj Hospital, Division of Nephrology, Department of Medicine, Mahidol University, Bangkok, Thailand.
J Viral Hepat. 2021 Feb;28(2):364-372. doi: 10.1111/jvh.13420. Epub 2020 Nov 2.
Long-term use of tenofovir disoproxil fumarate (TDF) can induce renal dysfunction that requires TDF dose reduction. Previous studies showed that systemic drug use exerts a threefold higher risk of moderate renal impairment. This study aimed to compare viral control between two tenofovir dose reduction regimens in chronic hepatitis B (CHB) patients with moderate renal impairment from TDF-induced renal dysfunction. This noninferiority, randomized controlled study was conducted at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Virologically suppressed CHB patients treated with TDF who had moderate renal impairment were randomly allocated to receive TDF 300 mg either every 48 or 72 hours. Forty-six patients (67.4% male) with a mean age of 62.8 ± 7.8 years were enrolled. Among all patients, 34.8% were HBeAg-positive, and 23.9% had cirrhosis. All included patients completed 12 months of follow-up. No patients had virological breakthrough. After dose reduction, estimated glomerular filtration rate (eGFR) was improved in both groups, but a higher proportion of patients had an eGFR > 60 mL/min/1.73 m in the TDF every 72 hours group. Other renal parameters, including serum phosphate, tubular maximal reabsorption for phosphate per GFR, urine protein-to-creatinine ratio, urine sugar and urine neutrophil gelatinase-associated lipocalin, were not significantly different between groups. Among TDF-treated CHB patients with TDF-induced moderate renal impairment, more aggressive dose reduction in TDF from every 48 hours to every 72 hours did not affect virological breakthrough. A higher proportion of patients in the TDF every 72 hours group had improvement in renal function.
长期使用富马酸替诺福韦二吡呋酯（TDF）可引起肾功能障碍，需要减少 TDF 剂量。先前的研究表明，全身用药会使中度肾功能损害的风险增加三倍。本研究旨在比较 TDF 诱导的肾功能障碍导致的中度肾功能损害的慢性乙型肝炎（CHB）患者中两种 TDF 剂量减少方案的病毒控制情况。这项非劣效性、随机对照研究在泰国曼谷玛希隆大学 Siriraj 医院医学系进行。接受 TDF 治疗且有中度肾功能损害的病毒学抑制的 CHB 患者被随机分配接受 TDF 300mg，每 48 小时或 72 小时一次。共有 46 名（67.4%为男性）患者，平均年龄 62.8±7.8 岁。所有患者中，34.8%为 HBeAg 阳性，23.9%有肝硬化。所有纳入的患者均完成了 12 个月的随访。无患者发生病毒学突破。减少剂量后，两组的估计肾小球滤过率（eGFR）均有所改善，但 TDF 每 72 小时组中 eGFR>60ml/min/1.73m 的患者比例更高。其他肾功能参数，包括血清磷酸盐、GFR 下的磷酸盐最大重吸收量、尿蛋白/肌酐比值、尿糖和尿中性粒细胞明胶酶相关脂质运载蛋白，两组间无显著差异。在 TDF 诱导的中度肾功能损害的 TDF 治疗的 CHB 患者中，更积极地将 TDF 剂量从每 48 小时减少至每 72 小时不会影响病毒学突破。TDF 每 72 小时组中肾功能改善的患者比例更高。
