核苷(酸)类似物治疗应答不佳转为富马酸丙酚替诺福韦治疗慢性乙型肝患者的早期临床观察  

Efficacy and safety of switching to tenofovir alafenamide fumarate from poor response to prior nucleos(t)ide analogue treatment in chronic hepatitis B patients

作　　者：陈妤 吕涛 韩少伟 谭霭明 司徒伟基 Chen Yu;Lyu Tao;Han Shaowei;Tan Aiming;Seto Wai-Kay(Department of Gastroenterology and Hepatology,The University of Hong Kong-Shenzhen Hospital,Guangdong Shenzhen 518000 China;Department of Clinical Pharmacy,The University of Hong Kong-Shenzhen Hospital,Guangdong Shenzhen 518000,China)

机构地区：[1]香港大学深圳医院消化与肝病科,广东深圳518000 [2]香港大学深圳医院临床药学科,广东深圳518000

出　　处：《新发传染病电子杂志》2022年第2期41-46,共6页Electronic Journal of Emerging Infectious Diseases

基　　金：香港大学深圳医院高水平医院建设科研培育计划重点项目(HKUSZH201902005)。

摘　　要：目的探讨核苷(酸)类似物(NAs)治疗应答不佳转为富马酸丙酚替诺福韦(TAF)治疗慢性乙型肝炎(CHB)患者的早期疗效和安全性。方法回顾性收集2019年4月至2020年1月就诊于香港大学深圳医院连续接受各种类型NAs治疗≥48周的CHB患者换用TAF继续治疗的病例资料,比较既往NAs长期治疗后换用TAF治疗12周的HBV应答率(HBV DNA<20IU/ml)、ALT复常率(男性<35U/L,女性<25U/L)、肾功能、血脂等水平的变化,以及转换TAF后对不同CKD分期CHB患者肾小球滤过率(eGFR)的影响。结果74例经治CHB患者[77%男性,年龄(49.55±10.52)岁,包括既往替诺福韦酯(TDF)治疗38例,恩替卡韦(ETV)治疗30例,其他类型NAs治疗6例],换用TAF抗病毒治疗12周,总体完全病毒学应答(HBV DNA<20IU/ml)率71.62%(53/74例)较基线40.54%(30/74例)显著升高(P<0.001)。血清中位ALT水平21.80(15.20,34.85)U/L较基线28.90(19.52,42.70)U/L下降(P=0.016),ALT复常率74.32%(55/74例)较基线56.76%(42/74例)明显升高(P=0.038)。但不同类型NAs转为TAF治疗HBV病毒应答率及ALT复常率无差别。在安全性方面,与基线相比换用TAF治疗12周后总体eGFR有轻微升高,但差异无统计学意义(P>0.05)。处于CKD 2期轻度肾损害患者转换TAF治疗12周后eGFR较基线明显改善[(79.37±10.82)ml/(min·1.73m^(2))比(72.23±9.11)ml/(min·1.73m^(2)),P=0.017]。结论CHB患者既往接受NAs治疗转换为TAF后均能有更显著的病毒应答及生化应答,总体安全性良好,并可改善轻度肾损害CHB患者的肾功能。Objective We aimed to evaluate the early effectiveness and the renal safety after switching from long-term nucleos(t)ide anologues(NAs)treatment to Tenofovir alafenamide fumarate(TAF)in patients with chronic HBV infection.Method We followed up consecutive chronic hepatitis B(CHB)virus infection patients with≥12 months of prior NAs therapy who were switched to TAF 25 mg daily at the University of Hong Kong-Shenzhen Hospital from April 2019 to January 2020.Endpoints such as serum HBV DNA undetectability(HBV DNA<20IU/ml),ALT normalization(upper limit of normal:male 35U/L,female 25U/L)and renal function safety were assessed at 12 weeks after switching.Renal function was evaluated by serum creatinine and estimated glomerular filtration rate(eGFR by CKD-EPI).Result Seventy-four CHB patients(77%male,mean age 49.55±10.52)were recruited.Serum HBV DNA undetectability rates increased from 40.54%at switching to 71.62%at 12 weeks(P<0.001).ALT normalization rates also increased from 56.76%to 74.32%after 12 weeks(P=0.038).Median serum ALT level decreased significantly from 28.90(19.52,42.70)to 21.80(15.20,34.85)(P=0.016).There was a small but not significant improvement in eGFR at week 12 compared to baseline.For the subgroup stage 2 chronic kidney disease(CKD)at TAF-switching,there was a significant improvement in mean eGFR after 12 weeks[(79.37±10.82)ml/(min·1.73m^(2))vs(72.23±9.11)ml/(min·1.73m^(2)),P=0.017).Conclusion Switching from prior NAs to TAF was effective for maintaining virological suppression and ALT normalization in CHB,and can lead to improvements in renal function in patients with mild chronic kidney disease.

关 键 词：富马酸丙酚替诺福韦 乙型肝炎病毒 核苷(酸)类似物 恩替卡韦 替诺福韦 

分 类 号：R512.62[医药卫生—内科学]