The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients  

慢性乙型肝炎患者核苷(酸)类似物停药96周的临床结局

作　　者：Wen-Xiong Xu Yang-Mei Li Jian-Guo Li Yong-Yu Mei You-Ming Chen Xue-Jun Li Chao-Shuang Lin Hong Deng Zhi-Xin Zhao Dong-Ying Xie Zhi-Liang Gao Liang Peng 

机构地区：[1]Department of Infectious Diseases,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [2]Guangdong Key Laboratory of Liver Disease Research,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [3]Department of Prevention and Health Care,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,P.R.China

出　　处：《Gastroenterology Report》2021年第4期313-322,I0002,共11页胃肠病学报道（英文）

摘　　要：Background:Chronic hepatitis B(CHB)patients have a high virological relapse rate after cessation of nucleos(t)ide analog(NA)treatment,but the clinical outcome remains unclear.This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs.Methods:This study was a prospective trial;74 eligible patients were enrolled.The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline.Symptoms,biochemical(aspartate aminotransferase[AST],alanine aminotransferase[ALT],total bilirubin,urea nitrogen,creatinine),virological data(hepatitis B surface antigen[HBsAg],hepatitis B e antigen[HBeAg],hepatitis B e antibody[HBeAb],hepatitis B virus[HBV]DNA levels),and color Doppler ultrasound examination results were recorded and analysed.Results:After NA cessation,19 cases were HBsAg-negative without relapse during the 96-week follow-up.Of the 55 cases of HBsAg-positive after cessation,four types of clinical outcomes were observed.Twelve patients had no relapse during the 96-week follow-up(type A,21.8%),7 patients underwent virological relapses but spontaneously had a non-virological relapse(type B,12.7%),10 patients maintained virological relapse(type C,18.2%),and 26 patients turned to clinical relapse,received NA retreatment,and achieved ALT normalization and negative conversion of HBV DNA within 12 months(type D,47.3%).The 2-year overall cumulative rates of virological and clinical relapses were 58.1%and 24.3%,respectively.Independent factors associated with virological relapse were duration of negative HBV DNA,EOT(end of treatment)HBsAg,and original status of HBeAg.The EOT HBsAg was also an independent factor for clinical relapse.Conclusions:There are four types of clinical outcomes in patients with CHB after cessation of NA treatment.Further research is needed to explore the mechanism of different clinical outcomes.The EOT HBsAg level is an independent factor associated with both virological and cli背景:慢性乙型肝炎患者核苷(酸)类似物停药后病毒学复发率高,但是临床结局仍不明确。本研究旨在探讨慢性乙肝患者核苷(酸)类似物停药96周的临床结局,以及复发危险因素。方法:前瞻性入组74例慢性乙肝患者。根据2012年亚洲-太平洋肝病学会指南,所有患者进行核苷(酸)类似物停药和随访。记录症状、生化指标(谷草转氨酶、谷丙转氨酶、总胆红素、尿素氮、肌酐)、病毒学标记物(乙肝表面抗原、乙肝e抗原、乙肝e抗体、乙肝DNA水平)、彩超检查结果和复发情况。结果:停药后,19例乙肝表面抗原阴性患者在96周随访中无复发。55例乙肝表面抗原阳性的患者可以观察到4种临床结局:12例无复发(A型,占21.8%);7例虽出现病毒学复发但自行转为无病毒学复发状态(B型,占12.7%);10例保持病毒学复发状态(C型,占18.2%);26例出现临床复发,再次应用核苷酸类似物抗病毒治疗,并于12个月内丙氨酸氨基转移酶恢复正常且乙肝病毒DNA转阴(D型,占47.3%)。2年累计病毒学复发率和临床复发率分别为58.1%和24.3%。病毒学复发的独立危险因素为停药前乙肝病毒DNA转阴的持续时间、停药时乙肝表面抗原的滴度以及抗病毒治疗前乙肝e抗原的状态。临床复发的独立危险因素为停药时乙肝表面抗原的滴度。结论:慢性乙型肝炎患者核苷(酸)类似物停药后有4种临床结局,需要进一步研究不同临床结局发生的机制。停药时乙肝表面抗原的滴度是病毒学复发和临床复发的独立危险因素。

关 键 词：chronic hepatitis B nucleos(t)ide analogs CESSATION RELAPSE hepatitis B virus 

分 类 号：R512.62[医药卫生—内科学]