核苷（酸）类药物初始抗病毒治疗慢性乙型肝炎患者144周疗效和对肾功能的影响

Efficacy and safety of long-term nucleos （t） ide analogue initial treatment in patients with chronic hepatitis B

目的观察核苷（酸）类药物（NAs）长期抗病毒治疗对慢性乙型肝炎（CHB）患者肾功能的影响。方法选取2013年3月至2016年8月浙江省人民医院收治的202例初治CHB患者作为研究对象，根据患者选用的抗病毒药物分为6组，阿德福韦酯组（ADV，n＝43），恩替卡韦组（ETV，n＝44），拉米夫定组（LAM，n＝25），替比夫定组（LDT，n＝23），LDT＋ADV组（n＝22），LAM＋ADV组（n＝45）。回顾性分析患者治疗后第48、96和第144周的HBV DNA转阴率、HBeAg血清学转换率，以及肾小球滤过率（eGFR）等指标，采用χ2检验和重复测量资料的方差分析对数据进行比较，并采用多因素Logistic回归分析引起CHB患者肾功能损害的相关危险因素。结果治疗144周，ETV和LDT组HBV DNA转阴率高于ADV组（P值均〈0.01）。ADV、ETV、LAM和LAM＋ADV组患者的eGFR水平随时间均呈下降趋势，LDT和LDT＋ADV组患者的eGFR则呈升高趋势（F时间＝3.939，F分组＝3.983，P〈0.01或〈0.05）。在第96周和第144周，LDT和LDT＋ADV组的eGFR水平较ADV、ETV、LAM及LAM＋ADV升高（P〈0.05）。多因素Logistic回归分析显示，年龄≥40岁[χ2＝16.145，OR＝4.452，95%可信区间（CI）2.149～9.223]，基线eGFR轻度受损（χ2＝16.449，OR＝4.336，95% CI 2.144～8.891）和ADV（χ2＝5.837，OR＝5.280，95%CI 1.369～20.365）为CHB患者肾功能损伤的独立危险因素。结论LDT单用或联合ADV治疗可改善肾功能，这为长期合理使用NAs抗病毒治疗提供参考依据。

ObjectiveTo evaluate the efficacy and safety of long-term nucleos（t）ide analogue treatment in patients with chronic hepatitis B （CHB）.MethodsTwo hundred and two initially treated patients with CHB admitted in Zhejiang Provincial People’s Hospital during March 2013 and August 2016 were enrolled in the study. Patients were divided into six groups according to the different antiviral therapy： adefovir group （ADV, n=43）, entecavir group （ETV, n=44）, lamivudine group （LAM, n=25）, telbivudine group （LDT, n=23）, LDT＋ ADV group （n=22）, and LAM＋ ADV group （n=45）. HBV DNA negative conversion rate, HBeAg serological conversion rate and estimated glomerular filtration rate （eGFR） at baseline and at 48th, 96th, 144th wk of treatment were measured. Chi-square test and repeated measure of ANOVA were used to analyze the data. Multivariate Logistic regression analysis was applied to detect the relevant risk factors of renal dysfunction in CHB patients. ResultsAfter treatment for 144 wks, the HBV DNA negative conversion rates in ETV and LDT group were higher than that in ADV group （both P〈0.01）, the levels of eGFR in ADV, ETV, LAM and LAM＋ ADV group were declined with time, while the eGFR levels in LDT and LDT＋ ADV group were increased with time （Ftime=3.939, Fgroup=3.983, P〈0.01 or 〈0.05）. After treatment for 96 wks and 144 wks, the levels of eGFR were higher in LDT and LDT＋ ADV group than those in other groups, respectively （all P〈0.05）. Multivariate Logistic regression analysis showed that age≥40 （χ2=16.145, OR=4.452, 95%CI 2.149-9.223, P〈0.05）, mild abnormality of eGFR at baseline （χ2=16.449, OR=4.336, 95%CI 2.144-8.891, P〈0.05）, and ADV treatment （χ2=5.837, OR=5.280, 95%CI 1.369-20.365, P〈0.05） were independent risk factors of renal dysfunction in CHB patients. ConclusionLDT long-term monotherapy or combination with ADV may improve renal function for patients with CHB, which provides a reference for long-term treatment of CHB patients with nucleos（t）ide analogues.