摘要
目的比较核苷(酸)类似物(NAs)单药和联合治疗在乙型肝炎e抗原(HBeAg)阳性且高病毒载量慢性乙型肝炎(CHB)患者中的抗病毒疗效和肾脏安全性。方法共纳入353例初治HBeAg阳性且高病毒载量的CHB患者,根据治疗方案分为5组,有4个单药治疗组和1个联合治疗组,分别为:恩替卡韦(ETV)组88例、富马酸替诺福韦二吡呋酯(TDF)组135例、富马酸丙酚替诺福韦(TAF)组34例、艾米替诺福韦(TMF)组25例和ETV联合TDF(ETV+TDF)组71例。采用回顾性队列研究设计,分析各组治疗24、48周HBV DNA水平、血清学(HBsAg、HBeAg水平)、肾功能指标(血Scr水平、eGFR)及48周HBsAg阴转率、HBeAg血清转换率和HBV DNA阴转率(HBV DNA<20 IU/ml),并通过多因素Logistic回归分析HBV DNA阴转的影响因素。结果24周时,ETV+TDF组HBV DNA水平低于ETV组(P<0.05),但与TDF、TAF、TMF组相近(P>0.05);48周时,ETV+TDF组的HBV DNA水平低于所有单药治疗组(P<0.05);TDF、TAF和TMF组的HBV DNA水平相近(P>0.05);ETV组HBV DNA水平高于其余4组(P<0.05)。ETV、TDF、TAF、TMF、ETV+TDF组HBV DNA阴转率分别为31.82%、51.11%、52.94%、56.00%、78.87%,ETV+TDF组的HBV DNA阴转率优于所有单药治疗组(P<0.05),TDF、TAF和TMF 3组HBV DNA阴转率相似,均优于ETV单药治疗组(P<0.05)。多因素分析显示,基线HBsAg低水平(OR=0.430,P=0.004)、基线ALT高值(OR=2.389,P<0.001)及联合治疗方案(OR=6.239,P<0.001)为治疗48周时HBV DNA阴转的独立预测因素。48周时ETV+TDF组HBsAg水平低于ETV组[(3.65±0.85)vs(3.88±0.64),P<0.05]。ETV+TDF组HBsAg阴转率1.41%(1/71),其余组阴转率均为0。各组间HBeAg血清转换率、血Scr及eGFR相互比较,差异均无统计学意义(P>0.05)。结论对于HBeAg阳性且高病毒载量CHB患者,ETV联合TDF方案较单药治疗可显著增强抗病毒疗效,且未增加肾脏不良事件风险,提示联合治疗可作为该类人群的优选策略。
Objective To compare the antiviral efficacy and renal safety of nucleoside analogs(NAs)monotherapy versus combination therapy in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB)patients with high viral load.Methods This study enrolled a total of 353 treatment-na ve HBeAg-positive chronic hepatitis B(CHB)patients with high viral load,the treatment regimen was divided into 5 groups,consisting of 4 monotherapy groups and 1 combination therapy group as follows:88 cases in the Entecavir(ETV)group,135 cases in the Tenofovir Disoproxil Fumarate(TDF)group,34 cases in the Tenofovir Alafenamide Fumarate(TAF)group,25 cases in the Tenofovir Amibufenamide(TMF)group,and 71 cases in the ETV combined with TDF(ETV+TDF)group.A retrospective cohort study design was adopted to analyze HBV DNA levels,serological indicators(HBsAg and HBeAg levels),renal function indicators(serum Scr levels,eGFR)at 24 and 48 weeks of treatment across various groups,as well as the HBsAg clearance rates,HBeAg seroconversion rates and HBV DNA suppression rates(HBV DNA<20 IU/ml)at 48 weeks across the groups.Multivariate logistic regression analysis was conducted to identify the influencing factors for HBV DNA suppression.Results At 24 weeks,the HBV DNA level in the ETV+TDF combination group was significantly lower than that in the ETV monotherapy group(P<0.05),and was similar to the HBV DNA levels in the TDF,TAF,and TMF groups(P>0.05).At 48 weeks,the HBV DNA levels in the ETV+TDF combination therapy group was significantly lower than those in all monotherapy groups(P<0.05).The HBV DNA levels in the TDF,TAF,and TMF monotherapy groups were similar(P>0.05).The HBV DNA level in the ETV group was higher than those in the remaining four groups(P<0.05).The HBV DNA suppression rates of the ETV,TDF,TAF,TMF and ETV+TDF groups were 31.82%,51.11%,52.94%,56.00%,and 78.87%,respectively,the HBV DNA suppression rate in the ETV+TDF combination therapy group was significantly better than those in all monotherapy groups(P<0.05),the rates of HBV DNA suppression were similar among the TDF,TAF,and TMF groups,and all were superior to that of the ETV monotherapy group(P<0.05).Multivariate analysis revealed that low baseline HBsAg levels(OR=0.430,P=0.004),high baseline ALT levels(OR=2.389,P<0.001),and the combination therapy regimen(OR=6.239,P<0.001)were independent predictors of HBV DNA suppression at 48 weeks of treatment.The reduction in HBsAg levels in the ETV+TDF group was significantly greater than that in the ETV monotherapy group[(3.65±0.85)vs(3.88±0.64),P<0.05].The HBsAg clearance rate in the ETV+TDF group was 1.41%(1/71),while the HBsAg clearance rates in the other groups were all 0%.There were no statistically significant differences in HBeAg seroconversion rates,blood Scr levels,and eGFR levels among the groups(P>0.05).Conclusion For HBeAg-positive chronic hepatitis B(CHB)patients with high viral load,the combination therapy of ETV and TDF significantly enhances viral suppression compared to monotherapy,without increasing the risk of renal adverse events.This suggests that the combination therapy can be considered a preferred strategy for this specific patient population.
作者
丁秀丽
尹华发
崔小玲
Ding Xiuli;Yin Huafa;Cui Xiaoling(Dept of Infectious Diseases,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Dept of Infectious Diseases,Second Affiliated Hospital of Bengbu Medical University,Bengbu 233000;Dept of Infectious Diseases,Tongling People′s Hospital,Tongling 244000)
出处
《安徽医科大学学报》
北大核心
2025年第6期1134-1139,1148,共7页
Acta Universitatis Medicinalis Anhui
基金
国家科技重大专项(编号:2018ZX10302-206)。
关键词
慢性乙型肝炎
高病毒载量
核苷(酸)类药物
单药
联合
抗病毒治疗
chronic hepatitis B
high viral load
nucleoside(acid)drugs
monotherapy
combination therapy
antiviral therapy
