核苷(酸)类似物治疗慢性乙型肝炎患者HBeAg持续阳性的临床特征分析

Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues

目的探讨核苷(酸)类似物治疗慢性乙型肝炎患者HBeAg持续阳性的临床特征。方法采用回顾性分析,按照数据类型的不同,使用独立样本t检验,Mann-Whitney U检验、χ^(2)检验或Fisher精确概率法。收集2009年1月至2018年12月中山三院感染科随访病例库中慢性乙型肝炎患者资料,随访4年,按照HBeAg转阴的时间,将患者HBsAg≤3年转阴(A组)及>3年转阴或持续阳性(B组)分为两组,分别为87、145例。对两组患者的年龄、性别、家族史及基线与复诊过程中的肝生物化学指标等资料进行统计学分析。结果两组患者的性别、年龄、肝硬化家族史、肝癌家族史、治疗前肝硬化情况、治疗前合并脂肪肝情况及基线HBsAg、抗-HBc、丙氨酸转氨酶、白蛋白、总胆红素差异均无统计学意义(P值均>0.05)。基线时B组HBV DNA和HBeAg显著高于A组,P值均≤0.001。基线时A组天冬氨酸转氨酶和γ-谷氨酰转移酶显著高于B组。两组患者乙型肝炎家族史比例B组(69.0%)明显高于A组(50.6%),差异有统计意义(P=0.005);B组母亲患乙型肝炎比例(25.5%)显著高于A组(11.5%),P=0.010。治疗过程中B组HBV DNA定量在0.5年和1年时显著高于A组(P≤0.002);HBV DNA<100 IU/ml的比例在6个月及1年时差异有统计学意义(χ^(2)=30.327,P<0.001和χ^(2)=11.779,P=0.001)。在第2年和第4年时,B组HBsAg水平显著高于A组,P<0.05。在治疗全程,B组HBeAg水平显著高于A组(P<0.001)。共有7例患者在随访中发生了肝硬化或肝癌,其中A组3例,B组4例(P>0.05)。结论HBeAg阳性的慢性乙型肝炎患者长期核苷(酸)类似物治疗时有部分患者HBeAg呈持续阳性,这部分患者有乙型肝炎家族史及母亲患有乙型肝炎的比例显著较高,HBV DNA早期(1年及以内)复常率低等特点。

Objective To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues.Methods A retrospective analysis was performed according to different data types.An independent sample t-test,Mann-Whitney U test,chi-square test,or Fisher's exact probability method were used.Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups,A and B,with 87 and 145 cases respectively,according to the duration of HBeAg-negativity≤3 and persistent positivity>3 years.Statistical analysis was conducted on the age,gender,family history,baseline,follow-up visit duration,liver function,and other data among the two patient groups.Results There were no statistically significant differences in gender,age,family history of liver cirrhosis,family history of liver cancer,liver cirrhosis condition before treatment,fatty liver disease combined condition before treatment,baseline HBsAg,anti-HBc,alanine aminotransferase,albumin,or total bilirubin between the two groups of patients(P>0.05).HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline,with P≤0.001.Aspartate aminotransferase andγ-glutamyl transferase were significantly higher in group A than those in group B at baseline.The proportion of family history of hepatitis B was significantly higher in group B(69.0%)than that in group A(50.6%)among the two groups of patients,and the difference was statistically significant(P=0.005).The proportion of mothers with hepatitis B was significantly higher in group B(25.5%)than in group A(11.5%),P=0.010.During the treatment process,the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years(P≤0.002).The proportion of HBV DNA<100IU/ml was also significantly different at six months and one year(χ^(2)=30.327,P<0.001 and χ^(2)=11.779,P=0.001).The HBsAg level was higher in group B than that of group A in the second and fourth years,P<0.05.During the entire treatment process,the HBeAg level was significantly higher in group B than that in group A(P<0.001).A total of seven cases developed liver cirrhosis or cancer during follow-up,including three cases in group A and four cases in group B(P>0.05).Conclusion HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues.Accordingly,a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages(within a year or less).