恩替卡韦经治后低病毒血症的慢性乙型肝炎患者序贯联合富马酸丙酚替诺福韦治疗的疗效及影响因素分析  

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

作　　者：刘丽萍 邬小萍[1] 蔡天盼 王亮[1] 孙俊 梁佳圆 马仕鹏 甘厦 阮宁杭 葛善飞[1] Liu Liping;Wu Xiaoping;Cai Tianpan;Wang Liang;Sun Jun;Liang Jiayuan;Ma Shipeng;Gan Xia;Ruan Ninghang;Ge Shanfei(Department of Infectious Diseases,First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Information Office of the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Medical College of Nanchang University,Nanchang 330031,China)

机构地区：[1]南昌大学第一附属医院感染性疾病科,南昌330006 [2]南昌大学第一附属医院信息处,南昌330006 [3]南昌大学医学院,南昌330031

出　　处：《中华肝脏病杂志》2023年第2期118-125,共8页Chinese Journal of Hepatology

基　　金：江西省自然科学基金资助项目(2021ACB206010)。

摘　　要：目的观察恩替卡韦(ETV)经治后低病毒血症(LLV)的慢性乙型肝炎患者序贯或联合富马酸丙酚替诺福韦(TAF)的疗效及影响因素。方法回顾性收集2020年1月至2022年9月于南昌大学第一附属医院感染科的经ETV抗病毒治疗的慢性乙型肝炎患者126例,根据治疗期间的HBV DNA水平,将患者分为完全病毒学应答组(n=84)和LLV组(n=42),对两组患者基线及48周的临床特征和实验室指标进行单因素分析。根据LLV组患者继续抗病毒治疗方案分为3组:续用ETV为对照组、换用TAF为序贯组、ETV联合TAF为联合组,并持续抗病毒治疗至96周。对3组患者48周的资料进行单因素方差分析,比较3组患者96周抗病毒治疗后HBV DNA转阴率、HBeAg转阴率、丙氨酸转氨酶、肌酐和肝硬度测定值。用多因素logistic回归分析LLV患者96周HBV DNA未转阴发生的独立影响因素,用受试者操作特征曲线评估预测LLV患者96周HBV DNA未转阴发生的效能。运用KaPlan-Meier分析LLV患者的DNA累积转阴率,用Log-Rank检验进行比较;动态观察治疗期间HBV DNA和HBV DNA转阴率。结果完全病毒学应答组与LLV组单因素分析结果显示基线时年龄、人体质量指数、HBeAg阳性率、HBV DNA、HBsAg、丙氨酸转氨酶、天冬氨酸转氨酶、肝硬度测定值差异均有统计学意义(P值均<0.05)。3组LLV患者48周单因素方差分析结果显示差异均无统计学意义(P值均>0.05);96周治疗后序贯组及联合组HBV DNA转阴率明显高于对照组(88.89%比41.18%、85.71%比41.18%,χ^(2)=10.404,P=0.006),HBeAg转阴率高于对照组,差异无统计学意义(P值>0.05);序贯组及联合组的丙氨酸转氨酶、肌酐、肝硬度测定值与对照组相比均有不同程度改善,差异均具有统计学意义(P值均<0.05)。48周后续用ETV和48周HBV DNA是LLV患者96周HBV DNA未转阴的独立危险因素(P值均<0.05)。48周HBV DNA的受试者操作特征曲线下面积为0.735(95%CI:0.578~0.891),cut-off值为2.63 Objective To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate(TAF)after treatment with entecavir(ETV)in patients with chronic hepatitis B(CHB)with low-level viremia(LLV).Methods 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected.Patients were divided into a complete virologic response(CVR)group(n=84)and a low-level viremia(LLV)group(n=42)according to the HBV DNA level during treatment.Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis.Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks:continued use of ETV as a control group;replacement of TAF as a sequential group;and combination of ETV and TAF as a combined group.The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks.HBV DNA negative conversion rate,HBeAg negative conversion rate,alanine aminotransferase(ALT),creatinine(Cr),and liver stiffness test(LSM)were compared among the three groups after 96 weeks of antiviral treatment.Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks.Receiver operating characteristic curve(ROC)was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks.Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients,and the Log-Rank test was used for comparison.HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically.Results Univariate analysis showed statistically significant differences in age,BMI,HBeAg positivity rate,HBV DNA,HBsAg,ALT,AST,and LSM at baseline between the CVR group and the LLV gr

关 键 词：慢性乙型肝炎 低病毒血症 富马酸丙酚替诺福韦 序贯联合治疗 动力学变化 

分 类 号：R512.62[医药卫生—内科学]