慢性乙型肝炎患者乙型肝炎病毒DNA自发清除相关因素分析

摘要

目的 观察CHB患者HBV DNA自发清除的发生率以及研究影响HBV DNA自发清除的相关因素,探讨启动抗病毒的时机.方法 研究对象来源于2008年1月至2017年8月广西医科大学第一附属医院感染性疾病科慢性HBV感染者随访队列,选择符合入组条件的患者进行观察,分别在观察基线、第1个月、第3个月、第6个月检测其肝功能ALT、HBV DNA及HBV血清标志物指标,评价指标包括HBV DNA累积转阴率、HBeAg累积转阴率.多因素分析影响HBV DNA自发清除的相关因素.结果 本研究共入组患者116例,随访首次出现A L T升高,在未服用抗病毒药的情况下,观察6个月出现HBV DNA累积转阴率为12.9％,HBeAg累积转阴率22.5％;多因素分析结果表明,无HBV感染家族史、基线ALT水平>3×正常值上限(upper limit of normal,ULN)、HBV DNA水平<6 lg拷贝/mL的患者,其HBV DNA自发清除累积发生率更高,同时符合3个条件者转阴率达75％.结论 CHB患者首次出现ALT升高,在未服用抗病毒药物的情况下,部分患者可获得HBV DNA自发清除,而无乙型肝炎家族史者、基线ALT水平>3×ULN、HBV DNA水平<6 lg拷贝/mL,其HBV DNA自发清除累积发生率更高.%Objective To observe the incidence of spontaneous clearance of hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB) patients ,and to investigate the related factors of the spontaneous clearance of HBV DNA and to determine the time to start antiviral therapy .Methods Patients who met the inclusion criteria were recruited from the follow-up cohort of chronic HBV infection from January 2008 to August 2017 for observation .The liver function including alanine aminotransferase (ALT) levels ,HBV DNA load and serum markers of HBV were measured at baseline ,month 1 ,month 3 and month 6 of follow-up . Evaluation index included cumulative HBV DNA negative conversion rate and cumulative HBeAg negative conversion rate .Multivariable analysis was used to analyze the factors associated with the spontaneous clearance of HBV DNA .Results A total of 116 patients were recruited in this study .All the patients showed ALT level elevation at baseline .Without antiviral treatment ,the cumulative HBV DNA negative conversion rate was 12 .9％ after 6-month observation .HBeAg negative conversion rate was 22 .5％ .Multivariable analysis showed that patients without a family history of HBV infection ,baseline ALT level >3 times the upper limit of normal (ULN) and HBV DNA level <6 lg copies/mL had higher cumulative HBV DNA spontaneous clearance rate .HBV DNA negative conversion rate in patients whomet all the above three conditions was up to 75％ .Conclusions In CHB patients and ALT level elevation for the first time , some patients could achieve spontaneous clearance of HBV DNA without antiviral therapy .Patients without a family history of HBV infection ,baseline ALT level >3 ULN and HBV DNA level <6 lg copies/mL have higher rate of cumulative HBV DNA spontaneous clearance .