替诺福韦抗病毒治疗对慢性乙型肝炎患者肾功能的影响及危险因素分析

摘要/Abstract

摘要： 目的评估替诺福韦酯(tenofovir disoproxil,TDF)治疗慢性乙型肝炎(chronic hepatitis B,CHB)患者的肾脏安全性及其引起肾功能损伤的危险因素。方法收集了2016年11月至2019年10月在上海华山医院和上海嘉定区中心医院肝炎门诊113例接受TDF治疗的CHB患者,同时收集了65例接受恩替卡韦(entecavir,ETV)治疗的患者作为对照。收集患者在基线、治疗12和24个月时的临床资料及肾功能检查结果包括血肌酐及肾小球滤过率(eGFR),并比较两组之间发生肾功能损伤和远端肾小管功能障碍的发生率。结果治疗24个月后,TDF治疗组和ETV治疗组HBV DNA转阴率分别为92.9%和90.8%,ALT复常率分别为85.0%和83.1%和HBeAg的转阴率分别为55.5%和47.2%,差异无统计学意义(χ²=0.263,P=0.608;χ²=0.110, P=0.740;χ²=0.601,P=0.438)。TDF治疗组血肌酐水平较基线水平显著增高,平均增高(10.8±4.7) μmol/L (t=2.83,P=0.041),eGFR水平较基线出现显著的下降,平均下降(11.8±1.5)mL/min·1.732 (t=3.728, P=0.034)。共有17例(15.0%)患者出现肾功能损伤,没有患者出现慢性肾脏病(CKD)。7例患者出现了远端肾小管功能障碍。多因素logistic回归分析表明,年龄>50岁(OR:2.821,95%CI:1.084~7.342,P=0.034)、糖尿病(OR:2.072,95%CI:1.035~4.150,P=0.040)和既往阿德福伟酯治疗(OR:3.162,95%CI:1.182~7.737,P=0.024)是影响肾功能损伤的独立危险因素。结论在使用TDF治疗的CHB患者中,随着治疗时间的延长eGFR会出现下降的趋势并引起肾功能损伤;高龄、糖尿病和既往ADV的使用是出现肾功能损伤的危险因素。

关键词: 慢性乙型肝炎, 替诺福韦, 肾功能, 肾小球滤过率

Abstract: Objective To evaluate the renal safety of tenofovir disoproxil (TDF) in the treatment of chronic hepatitis B (CHB) patients and the risk factors for renal function damage. Methods A total of 113 CHB patients received TDF treatment were collected as TDF treatment group. 65 patients received entecavir (ETV) were collected as ETV treated control group. The patient's clinical data and renal function test were collected at baseline, and 12 and 24 months after treatment. Results After 24 months of treatment, there was no significant difference in the conversion rate of HBV DNA (92.9% in TDF group vs 90.8% in ETV group), the recovery rate of ALT (85.0% in TDF group vs 83.1% in ETV group) and the conversion rate of HBeAg (55.5% in TDF group vs 47.2% in ETV group) between the TDF treatment group and the ETV treatment group(χ²=0.263,P=0.608;χ²=0.110, P=0.740;χ²=0.601,P=0.438). At 24 months of treatment, the blood creatinine level in TDF treatment group was significantly increased, with an average increase of 10.8±4.7 μmol/L (t=2.83,P=0.041),whereas the eGFR level was significantly decreased from baseline, with an average decrease of 11.8±1.5 ml/min/1.732 (t=3.728, P=0.034). A total of 14 patients (12.4%) had renal function impairment (eGFR levels were≥25% lower than baseline), but no patients had chronic kidney disease (CKD). Seven patients developed proximal tubular renal dysfunction. Multivariate logistic regression analysis showed that those patients older than 50 years old (OR: 2.821, 95% CI: 1.084-7.342, P=0.034), with diabetes (OR: 2.072, 95% CI: 1.035-4.150, P=0.040) and with past experience of adefovir dipivoxil (ADV) treatment (OR: 3.162, 95% CI: 1.182-7.737, P=0.024) were independent risk factors associated with renal impairment. Conclusion In CHB patients treated with TDF, eGFR tends to decline and renal impairment may develop with the prolongation of treatment time. Oder age, diabetes, and previous ADV use are risk factors associated with renal impairment. Therefore, the renal function of patients receiving long-term TDF treatment should be carefully evaluated and monitored to prevent the occurrence of adverse reaction.

Key words: Chronic hepatitis B, Tenofovir, Renal function, Glomerular filtration rate

韩宗儒, 闵晓春, 沈启刚, 尹有宽, 王森. 替诺福韦抗病毒治疗对慢性乙型肝炎患者肾功能的影响及危险因素分析[J]. 肝脏, 2021, 26(11): 1216-1220.

HAN Zong-ru, MIN Xiao-chun, SHEN Qi-gang, YIN You-kuan, WANG Sen. The impact of antiviral treatment with tenofovir on the renal function of patients with chronic hepatitis B[J]. Chinese Hepatolgy, 2021, 26(11): 1216-1220.

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