HBsAg定量对慢性乙型肝炎服用核苷类似物抗病毒达治疗终点后远期疗效的评估价值

Value of HBsAg quantification in evaluation of long-term efficacy of nucleoside analogues for patients with chronic hepatitis B after antiviral therapy

目的 通过对慢性乙型肝炎患者服用核苷（酸）类抗病毒药物达停药终点后停药者,行乙型肝炎表面抗原定量（HBsAg）定期监测,观察其数值与远期复发率的关系,以指导临床医生合理选择停药时机.方法 选取2007年恩替卡韦从我国上市以来符合抗病毒治疗标准的慢性乙型肝炎患者进行随访观察,将符合2010版《慢性乙型肝炎防治指南》停药标准,并在2014年7月至2015年7月间停药的患者62例纳入观察对象;停药后第1、2、3、6、12月进行指标的监测,包括血清丙氨酸氨基转移酶（ALT）、乙型肝炎病毒DNA定量（HBVDNA）、HBsAg定量、超声等;收集资料时间截止到2016年7月.结果 单因素分析显示停药时HBsAg定量数值高、治疗达停药标准时间长、基线HBeAg阴性人群、停药时HBcAb定量水平数值高、基线ALT水平高,更容易发生停药后的复发（P值分别为0.004、0.028、0.009、0.003、0.013）.多因素回归分析显示停药时HBsAg定量水平（OR=6.31,P=0.032）、治疗达停药标准时间（OR=7.66,P=0.000）、停药时HBcAb定量水平（OR=7.91,P=0.027）、基线ALT水平（OR=4.33,P=0.008）是停药复发的独立危险因素.全部患者停药至随访结束时复发24例（38.71％）,停药后1月、2月、3月、6月、12月复发率分别为0、0、1.61％、17.74％、39.70％,复发最早发生在停药后3月,复发病例增多自停药后随访6月时开始.结论 停药时HBsAg定量水平、治疗达停药标准时间、停药时HBcAb定量水平、基线ALT水平为核苷（酸）类似物抗病毒治疗达停药终点后随访复发独立危险因素;抗病毒治疗达停药终点后继续治疗巩固时间越长,停药后复发概率越小.

Objective To observe the relationship between the quantity of hepatitis B surface antigen （HBsAg） and the long-term recurrence rate detecting the HBsAg at the termination of drug administration in patients treated by nucleoside analogues,and to guide the clinical doctors rationally choose the drug termination time.Methods The patients with chronic hepatitis B who were in accordance with the antiviral treatment standards since entecavir came into the market in China in 2007 were followed up and observed.And 62 patients stopped treatment according to the drug termination standards of Prevention and Treatment Guidelines of Chronic Hepatitis B （2010 Edition） from July,2014 to July,2015 were included as observation objects.1,2,3,6,and 12 months after drug termination,the serum alanine aminotransferase （ALT）,hepatitis B virus DNA quantitative （HBV DNA）,and HBsAg quantity were detected and the patients were examined by ultrasound.The data were collected before July,2016.Results Univariate analysis suggested that the high HBsAg quantity,long treatment time to drug withdrawal standard,big population with negative baseline HBeAg,high HBcAb quantity at drug termination,and the high baseline ALT level might cause recurrence after drug withdrawal（P=0.004,0.028,0.009,0.003,0.013）.And multivariate regression analysis showed that the HBsAg quantity at drug termination （OR=6.31,P=0.032）,the treatment time to drug withdrawal standard （OR=7.66,P=0.000）,the HBcAb quantity at drug termination （OR=7.91,P=0.027）,and the baseline ALT （OR=4.33,P=0.008） were independent risk factors for the relapse after drug withdrawal.24 cases （38.71%） relapsed at the end of the follow-up.The recurrence rates 1,2,3,6,and 12 months after drug termination were 0,0,1.61%,17.74%,and 39.70%,respectively.The recurrence first occurred 3 months after drug termination and occurred more 6 months after.Conclusions HBsAg quantity at drug termination,treatment time to drug withdrawal standard,HBcAb quantity at drug termination,and the baseline ALT are independent risk factors of chronic hepatitis B recurrence after the termination of treatment by nucleoside analogues.The recurrence rate decreases,as the continuous treatment after the termination of antiviral treatment prolongs.