尿β2-微球蛋白作为替诺福韦酯致慢性乙型肝炎患者近端肾小管功能损伤早期预测指标的临床价值

Clinical value of urinary β2-microglobulin as an early predictor of proximal tubular dysfunction induced by tenofovir disoproxil in patients with chronic hepatitis B

目的探讨替诺福韦酯(tenofovir disoproxil,TDF)导致慢性乙型肝炎(chronic hepatitis B,CHB)患者近端肾小管功能障碍(proximal tubular renal dysfunction,PRTD)的临床流行病学特征及尿β2-微球蛋白(β2 microglobulin,β2-MG)作为预测CHB患者TDF相关近端肾小管损伤标志物的临床价值。方法纳入2013年1月至2016年6月于首都医科大学附属北京地坛医院就诊的慢性乙型肝炎(chronic hepatitis B,CHB)患者62例为研究对象,其中32例接受阿德福韦酯(adefovir dipivoxil,ADV)联合恩替卡韦(entecavir,ETV)治疗,30例接受TDF治疗,疗程均为96周。出现PRTD即认为出现终点事件,患者需停止用药。比较两组患者PRTD的发生率以及PRTD患者和无PRTD患者尿β2-MG升高的发生率。结果 ADV+ETV组中12例(37.5%)出现PRTD,TDF组中3例(10.0%)出现PRTD,差异有统计学意义(χ~2=7.200,P=0.007)。PRTD患者中尿β2-MG升高的比例显著高于无PRTD患者(93.3%vs 6.4%;χ~2=43.198,P<0.001)。尿β2-MG预测TDF相关肾小管损伤的ROC曲线下面积为0.935。结论与ADV相比,TDF具有更高的肾脏安全性,尿β2-MG对慢性乙型肝炎患者TDF相关早期近端肾小管损伤具有较高的诊断价值。

Objective To investigate the clinical epidemiological characteristics of proximal renal tubular dysfunction(PRTD)of chronic hepatitis B(CHB)patients treated with tenofovir disoproxil(TDF)and the clinical value of urinaryβ2-microglobulin(β2-MG)as an early predictor of PRTD induced by TDF in patients with CHB.Methods A total of 62 patients with CHB were enrolled and observed in Beijing Ditan Hospital,Capital Medical University from January 2013 to June 2016.Among them,32 cases accepted adefovir dipivoxil(ADV)combined entecavir(ETV)therapy and 30 cases accepted TDF treatment.The course of treatment was 96 weeks.PRTD was regarded as the occurrence of terminal events,once occured,the patients should stop taking drugs.The incidence of PRTD in both groups and the incidence of urinaryβ2-MG in patients with PRTD and patients without PRTD were compared.Results Total of 12 patients(37.5%)were diagnosed as PRTD in ADV+ETV group,and 3 patients(10.0%)in TDF group,the difference was statistically significant(χ2=7.200,P=0.007).The proportion of urinaryβ2-MG increased in CHB patients with PRTD was significantly higher than that in CHB patients without PRTD(93.3%vs 6.4%;χ2=43.198,P<0.001).The area under the ROC curve for urineβ2-MG predicting TDF-associated PRTD was 0.935.Conclusion Compared with ADV,TDF has higher renal safety.Urinaryβ2-MG has a high diagnostic value for early proximal tubular injury associated with TDF in patients with chronic hepatitis B.