Abstract:

Objective　To explore the value of serum hepatitis B virus RNA (HBV RNA) level in predicting the relapse of chronic hepatitis B (CHB) after withdrawal of nucleoside (acid) drugs (NAs) antiviral treatment. Methods　A total of 160 patients with CHB who were treated in Yantai Qishan Hospital from January 2017 to January 2021 were selected, including 105 males and 55 females, with an age of (43.32±8.81) years old, all of whom received NAs antiviral treatment and met the drug withdrawal criteria. The patients' relapse after drug withdrawal was followed up, and the differences in the clinical data and HBV RNA between the patients with and without relapse after drug withdrawal were analyzed. t test and χ² test were used to analyze the differences in indicators between groups. Logistic regression analysis was used for multivariate analysis of risk factors of relapse after drug withdrawal, and the predictive value was analyzed by the receiver operating characteristic curve (ROC). Results　Followed up until February 2023, 46 patients had relapse after drug withdrawal, with a relapse rate of 28.75% (46/160). The age, rate of diabetes, baseline HBV DNA, baseline HBV RNA, and HBV RNA at the time of drug withdrawal in the relapse patients after drug withdrawal were (45.58±9.23) years old, 45.65% (21/46), (7.10±1.10) log copies/ml, (6.30±1.02) log copies/ml, and (2.40±0.87) log copies/ml, respectively, which were significantly higher than those in the patients without relapse after drug withdrawal [(40.12±9.11) years old, 19.30% (22/114), (6.15±1.03) log copies/ml, (5.17±1.00) log copies/ml, and (1.93±0.81) log copies/ml], with statistically significant differences (all P<0.05). Logistic regression analysis showed that age, diabetes, and HBV RNA at the time of drug withdrawal were the influencing factors for relapse in CHB patients after drug withdrawal (OR=1.939, 2.667, and 3.102; all P<0.05). The area under the curve of HBV RNA at the time of drug withdrawal predicting relapse in CHB patients after drug withdrawal was 0.777 (95%CI 0.706-0.849, P<0.05), the cutoff value was 1.61 log copies/ml, and the sensitivity and specificity were 88.50% and 54.80%, respectively. There were no statistically significant differences in the hepatitis B virus e antigen (HBeAg) negative, HBV DNA negative, and HBV RNA negative rates in the HBeAg positive relapsed and non-relapsed patients after treatment for 24 weeks, 48 weeks, and 72 weeks (all P>0.05). HBV DNA conversion was faster, while HBeAg and HBV RNA conversion was slower and more synchronous. Conclusion　The level of HBV RNA at the time of drug withdrawal is related to the relapse of CHB patients after NAs drug withdrawal, which has certain application value in predicting the relapse after drug withdrawal.

Key words:

Chronic hepatitis B, Hepatitis B virus RNA, Nucleoside (acid) drugs, Antiviral treatment, Relapse after drug withdrawal

摘要：

目的　探讨血清乙型肝炎病毒核糖核酸（hepatitis B virus RNA，HBV RNA）水平在预测核苷（酸）药物［nucleoside （acid） drugs，NAs］抗病毒治疗慢性乙型肝炎（chronic hepatitis B，CHB）停药复发中的价值。方法　回顾性选取2017年1月至2021年1月在烟台市奇山医院治疗的CHB患者160例，其中男105例、女55例，年龄（43.32±8.81）岁，均接受NAs抗病毒治疗，且达到停药标准。随访患者停药复发情况，分析停药复发和未复发患者临床资料、HBV RNA的差异。采用t检验、χ²检验分析组间指标差异，停药复发危险因素的多因素分析采用logistic回归分析，预测价值采用受试者工作特征曲线（ROC）分析。结果　截止2023年2月，停药复发患者46例，停药复发率28.75%（46/160）。停药复发患者年龄、合并糖尿病比例、基线乙型肝炎病毒脱氧核糖核酸（hepatitis B virus DNA，HBV DNA）、基线HBV RNA和停药时HBV RNA分别为（45.58±9.23）岁、45.65%（21/46）、（7.10±1.10）log copies/ml、（6.30±1.02）log copies/ml、（2.40±0.87）log copies/ml，均明显高于停药未复发患者的（40.12±9.11）岁、19.30%（22/114）、（6.15±1.03）log copies/ml、（5.17±1.00）log copies/ml、（1.93±0.81）log copies/ml，差异均有统计学意义（均P<0.05）。logistic回归分析显示，年龄、糖尿病、停药时HBV RNA是CHB患者停药复发的影响因素（OR=1.939、2.667、3.102，均P<0.05）。停药时HBV RNA预测CHB患者停药复发的曲线下面积为0.777（95%CI 0.706～0.849，P<0.05），截断值为1.61 log copies/ml，灵敏度和特异度分别为88.50%、54.80%。乙型肝炎病毒e抗原（hepatitis B virus e antigen，HBeAg）阳性停药复发和未复发患者治疗24周、48周、72周HBeAg转阴、HBV DNA转阴、HBV RNA转阴率比较，差异均无统计学意义（均P>0.05）；HBV DNA转归较快，而HBeAg和HBV RNA转归较慢，且较同步。结论　停药时HBV RNA水平与CHB患者NAs停药复发有关，在预测停药复发方面有一定应用价值。

关键词:

慢性乙型肝炎, 乙型肝炎病毒核糖核酸, 核苷（酸）药物, 抗病毒治疗, 停药复发