【摘要】 目的 分析比较恩替卡韦（ETV）与富马酸丙酚替诺福韦（TAF）对初治慢性乙型肝炎（CHB）患者肾功能的影响。方法 回顾性分析2019年9月—2023年11月于南昌大学第一附属医院感染科门诊接受ETV或TAF治疗至少48周的167例初治CHB患者临床资料。根据患者抗病毒药物分为ETV组（n=117）和TAF组（n=50）。为均衡基线临床资料，采用倾向性评分匹配（PSM）按照2∶1比例进行匹配分析，比较两组患者48周时肾小球滤过率（e GFR）水平及肾功能异常发生率。根据患者48周e GFR水平将患者分为肾功能正常组和异常组。计量资料两组间比较采用成组t检验或Mann-Whitney U检验；计数资料组间比较采用χ²检验或Fisher精确检验。采用多因素Logistic回归分析发生肾功能异常的影响因素，受试者工作特征曲线（ROC曲线）评估各指标预测发生肾功能异常的效能。采用Kaplan-Meier法分析肾功能异常累积发生率，并应用Log-rank检验进行比较。采用重复测量资料的方差分析比较CHB患者抗病毒治疗期间e GFR动态变化情况。结果 PSM成功匹配150例CHB患者，其中ETV组100例，TAF组50例。基线时，ETV组和TAF组一般资料比较，差异均无统计学意义（P值均>0.05），两组患者基线e GFR分别为（112.29±9.92） m L·min^-1·1.73 m^-2和（114.72±12.15） m L·min^-1·1.73 m^-2。48周时两组患者e GFR水平较基线均有下降，ETV组48周e GFR明显低于TAF组[（106.42±14.12） m L·min^-1·1.73 m^-2 vs（112.25±13.44） m L·min^-1·1.73 m^-2,t=-2.422,P=0.017]，肾功能异常发生率明显高于TAF组（17.00%vs 4.00%，χ²=5.092,P=0.024）。将患者分为肾功能正常组（n=131）与异常组（n=19）后，单因素分析结果显示，两组患者年龄（Z=-2.039,P=0.041）、治疗药物（ETV/TAF）（χ²=5.092,P=0.024）、基线e GFR水平（t=4.023,P<0.001）差异均有统计学意义；多因素Logistic回归分析显示，基线e GFR（OR=0.896,95%CI:0.841～0.955,P<0.001）和治疗药物（OR=5.589,95%CI:1.136～27.492,P=0.034）是发生肾功能异常的独立影响因素。基线e GFR预测CHB患者发生肾功能异常的ROC曲线下面积为0.781,cut-off值为105.24 m L·min^-1·1.73 m^-2，敏感度和特异度分别为73.68%、82.44%。Kaplan-Meier曲线分析结果显示，基线e GFR≤105.24 m L·min^-1·1.73 m^-2组患者肾功能异常累积发生率高于基线e GFR>105.24 m L·min^-1·1.73 m^-2组患者（χ²=22.330,P<0.001）;ETV组患者肾功能异常累积发生率高于TAF组患者（χ²=4.961,P=0.026）。随着抗病毒治疗启动，ETV组和TAF组患者e GFR均降低（F=5.259,P<0.001），但仅在48周时ETV组e GFR水平明显低于TAF组（t=-2.422,P=0.017）；在基线e GFR≤105.24 m L·min^-1·1.73 m^-2和基线e GFR>105.24 m L·min^-1·1.73 m^-2的两组患者中，e GFR亦下降（F=5.712,P<0.001），且基线及第12、24、36、48周两组患者e GFR比较，差异均有统计学意义（t值分别为-13.927、-9.780、-8.835、-9.489、-8.953,P值均<0.001）。结论 对于ETV或TAF初治的CHB患者，ETV抗病毒治疗48周时的肾损伤风险高于TAF治疗。更多还原

【Abstract】 Objective To investigate the influence of entecavir (ETV) versus tenofovir alafenamide fumarate (TAF) on renal function in previously untreated patients with chronic hepatitis B (CHB).Methods A retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023,and according to the antiviral drug used,they were divided into ETV group with 117 patients and TAF group with50 patients.In order to balance baseline clinical data,propensity score matching (PSM) was used for matching and analysis at a ratio of 2∶1,and the two groups were compared in terms of estimated glomerular filtration rate (e GFR) and the incidence rate of abnormal renal function at week 48.According to e GFR at week 48,the patients were divided into normal renal function group and abnormal renal function group.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups.The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function,and the receiver operating characteristic (ROC) curve was used to assess the performance of each indicator in predicting abnormal renal function.The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function,and the log-rank test was used for comparison.The analysis of variance with repeated measures was used to compare the dynamic changes of e GFR during antiviral therapy in CHB patients.Results After PSM matching,there were 100 patients in the ETV group and 50 patients in the TAF group.There were no significant differences in baseline clinical data between the ETV group and the TAF group (all P>0.05),with an e GFR level of 112.29±9.92 m L/min/1.73 m~2 in the ETV group and 114.72±12.15 m L/min/1.73 m~2 in the TAF group.There was a reduction in e GFR from baseline to week 48 in both groups,and compared with the TAF group at week 48,the ETV group had a significantly lower e GFR (106.42±14.12 m L/min/1.73 m~2 vs 112.25±13.44 m L/min/1.73 m~2,t=-2.422,P=0.017) and a significantly higher incidence rate of abnormal renal function (17.00%vs 4.00%，χ~2=5.092,P=0.024).After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients,the univariate analysis showed that there were significant differences between the two groups in age (Z=-2.039,P=0.041),treatment drug (ETV/TAF）（χ~2=5.092,P=0.024),and baseline e GFR level (t=4.023,P<0.001),and the multivariate Logistic regression analysis showed that baseline e GFR (odds ratio[OR]=0.896,95%confidence interval[CI]:0.841—0.955,P<0.001) and treatment drug(OR=5.589,95%CI:1.136—27.492,P=0.034) were independent influencing factors for abnormal renal function.Baseline e GFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients,with a cut-off value of 105.24m L/min/1.73 m~2,a sensitivity of 73.68%,and a specificity of 82.44%.The Kaplan-Meier curve analysis showed that the patients with baseline e GFR≤105.24 m L/min/1.73 m~2 had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline e GFR>105.24 m L/min/1.73 m~2（χ~2=22.330,P<0.001),and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group（χ~2=4.961,P=0.026).With the initiation of antiviral therapy,both the ETV group and the TAF group had a significant reduction in e GFR (F=5.259,P<0.001),but the ETV group only had a significant lower level of e GFR than the TAF group at week 48 (t=-2.422,P=0.017);both the baseline e GFR≤105.24 m L/min/1.73 m~2 group and the baseline e GFR>105.24 m L/min/1.73 m~2 group had a significant reduction in e GFR (F=5.712,P<0.001),and there was a significant difference in e GFR between the two groups at baseline and weeks 12,24,36,and48 (t=-13.927，-9.780，-8.835，-9.489,and-8.953,all P<0.001).Conclusion For CHB patients initially treated with ETV or TAF,ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.更多还原