恩替卡韦经治的慢性乙型肝炎患者发生低病毒血症危险因素及转换TAF治疗疗效研究

Risk factors of low-level viremia and rescue switch treatment to tenofovir alafenamide fumarate in entecavir-treated patients with chronic hepatitis B

目的分析恩替卡韦(ETV)经治慢性乙型肝炎(CHB)患者发生低病毒血症(LLV)的危险因素及转换富马酸丙酚替诺福韦(TAF)治疗的疗效。方法2020年1月~2022年12月我院收治的ETV经治的CHB患者158例,对获得完全病毒学应答(CVR)者继续口服ETV,对发生LLV者则转换为TAF治疗,两组均观察48 w。使用超敏PCR检测系统检测血清HBV DNA,使用全自动化学发光免疫分析仪检测血清HBeAg和HBsAg定量。应用Logistic回归分析影响ETV经治CHB患者发生LLV的危险因素。结果在纳入的经ETV治疗至少48 w的158例CHB患者中,发现LLV者55例(34.8%)和CVR者103例(65.2%);单因素分析发现体质指数、乙型肝炎家族史、合并代偿期肝硬化、基线HBV DNA载量、血清HBeAg阳性和血清HBsAg水平与ETV治疗发生LLV相关(P<0.05),多因素Logistic回归分析显示,基线血清HBV DNA高载量(OR:2.793,95%CI:1.579~4.940)、HBeAg阳性(OR:2.337,95%CI:1.455~3.756)和血清HBsAg高水平(OR:1.931,95%CI:1.338~2.786)是ETV治疗CHB患者发生LLV的独立危险因素(P<0.05);在TAF转换治疗48 w末,55例LLV患者获得CVR者36例(65.5%);LLV组血清ALT水平、HBV DNA载量和HBsAg定量仍显著高于CVR组【分别为37.2(19.1,57.0)U/L、(0.9±0.4)lg IU/ml和(3.9±0.6)lg IU/ml对33.5(17.6,39.2)U/L、(0.7±0.3)lg IU/ml和(3.1±0.5)lg IU/ml,P<0.05】。结论恩替卡韦治疗CHB患者基线血清HBV DNA高载量、HBeAg阳性和血清HBsAg定量水平高是发生LLV的危险因素,而大部分LLV患者转换TAF治疗可获得较好的病毒学应答率,值得进一步研究。

Objective The aim of this study was to investigate the risk factors of low-level viremia(LLV)and rescue switch treatment to tenofovir alafenamide fumarate(TAF)in entecavir(ETV)-treated patients with chronic hepatitis B(CHB).Methods A total of 158 patients with CHB were enrolled in our hospital between January 2020 and December 2022,and all were already had treated with ETV for at least 48 weeks.The patients who obtained complete virological response(CVR)continued the ETV treatment,and those with LLV were switched to TAF treatment.The patients in the two groups were observed for 48 weeks.Serum HBV DNA loads were detected by hypersensitive PCR detection system,serum HBeAg and HBsAg quantification were detected by full-automatic chemiluminescence immunoanalyzer.The risk factors of LLV in CHB patients undergoing ETV treatment were analyzed by multivariate Logistic regression analysis.Results Out of the 158 patients with CHB enrolled in this study,the LLV was found in 55 cases(34.8%)and the CVR in 103 cases(65.2%);the body mass index,family hepatitis B history,concomitant liver cirrhosis,baseline serum HBV DNA loads,serum HBeAg positive and serum HBsAg levels were correlated to the occurrence of LLV(P<0.05),and the multivariate Logistic regression analysis showed that the baseline serum HBV DNA loads(OR:2.793,95%CI:1.579-4.940),serum HBeAg positive(OR:2.337,95%CI:1.455-3.756)and serum HBsAg high levels(OR:1.931,95%CI:1.338-2.786)were the independent risk factors for LLV occurrence in ETV-treated patients with CHB(P<0.05);at the end of 48-week of TAF treatment,the CVR was obtained in 36 cases(65.5%)in 55 patients with LLV,and serum ALT level,HBV DNA load and HBsAg level in 55 patients with LLV were still significantly higher than those with CVR[37.2(19.1,57.0)U/L,(0.9±0.4)lg IU/ml and(3.9±0.6)lg IU/ml vs.33.5(17.6,39.2)U/L,(0.7±0.3)lg IU/ml and(3.1±0.5)lg IU/ml,respectively,P<0.05].Conclusion The high baseline serum HBV DNA loads, HBeAg positive and high HBsAg quantification might be the risk factors for LLV occurrence in ETV-treated patients with CHB and the rescue TAF treatment could get CVR in most of them, which warrants further clinical investigation.