恩替卡韦治疗的慢性乙型肝炎患者低病毒血症的影响因素

Influencing factors of low-level viremia in patients with chronic hepatitis B treated with Entecavir

目的了解恩替卡韦(ETV)治疗的慢性乙型肝炎(CHB)患者低病毒血症(LLV)的现况,探讨低病毒血症的影响因素。方法选取2021年4月—2021年12月于汕头大学医学院第一附属医院门诊口服恩替卡韦治疗1年以上,且HBV DNA定量检测<100 IU/mL的肝CHB患者,行高敏HBV DNA定量复测(检测下限10 IU/mL),根据检测结果将患者分为病毒学应答(VR)组及低病毒血症(LLV)组。收集患者的人口学资料和实验室检查资料。通过单因素分析和多因素logistic回归分析ETV治疗的CHB患者出现LLV的影响因素。结果共纳入CHB患者260例,VR组220例,LLV组40例。LLV的发生率中,男性为12.8%(25/195),低于女性的23.1%(15/65)(χ^(2)=3.939,P=0.047);服药依从性良好者为12.6%(30/239),低于依从性不佳者的47.6%(10/21)(χ^(2)=15.640,P<0.001);肝硬化者为8.8%(8/91),低于非肝硬化者的18.9%(32/169)(χ^(2)=4.675,P=0.031);HBeAg阳性者为30.0%(27/90),高于HBeAg阴性者的7.6%(13/170)(χ^(2)=22.587,P<0.001),LLV组基线病毒量为7.0 log 10 IU/mL,高于VR组的5.6 log 10 IU/mL(Z=-4.458,P<0.001)。多因素logistic回归分析表明,服药依从性不佳(OR=2.927,95%CI:1.078~7.949,P=0.035)、基线HBeAg阳性(OR=2.473,95%CI:1.064~5.747,P=0.035)、基线高HBV DNA载量(OR=1.441,95%CI:1.068~1.943,P=0.017)是恩替卡韦治疗的CHB患者出现LLV的独立危险因素(P<0.05)。结论在临床诊疗中,即使经过长时间ETV治疗,HBV DNA<100 IU/mL的CHB患者中仍有15.4%(40/260)存在LLV,依从性不佳、基线HBeAg阳性、病毒载量高是LLV的危险因素。

Objective To investigate the current status of low-level viremia(LLV)in Entecavir(ETV)-treated chronic hepatitis B(CHB)patients and explore the related factors of LLV.Methods The study was conducted from April 2021 to December 2021.CHB patients who were treated with ETV over one year in The First Affiliated Hospital of Shantou University Medical College and experienced LLV(HBV DNA<100 IU/mL)were enrolled for high-sensitivity HBV DNA detection(the lower limit of detection:10 IU/mL).According to the test results,they were divided into virological response(VR)group and LLV group.The demographic data and laboratory findings of patients were collected.Univariate analysis and multivariate logistic regression were used to analyze the related factors of LLV in CHB patients treated with long-term ETV.Results A total of 260 CHB patients were included,40 in the LLV group and 220 in the VR group.The incidence of LLV was 12.8%(25/195)in males,lower than 23.1%(15/65)in females(χ^(2)=3.939,P=0.047);was 12.6%(30/239)in patients with good compliance,lower than 47.6%(10/21)in patients with poor compliance(χ^(2)=15.640,P<0.001);was 8.8%(8/91)in cirrhotic patients,lower than 18.9%(32/169)in non-cirrhotic patients(χ^(2)=4.675,P=0.031);was 30.0%(27/90)in HBeAg-positive patients,higher than 7.6%(13/170)in HBeAg-negative patients(χ^(2)=22.587,P<0.001).The baseline virus load of the LLV group was higher when compared with the VR group(7.0 log10IU/mL vs.5.6 log10IU/mL,Z=-4.458,P<0.001).Multivariate logistic regression analysis showed that poor medication compliance(OR=2.927,95%CI:1.078~7.949,P=0.035),positive HBeAg(OR=2.473,95%CI:1.064-5.747,P=0.035)and high HBV DNA load(OR=1.441,95%CI:1.068-1.943,P=0.017)before treatment were independent risk factors for LLV in CHB patients treated with ETV.Conclusion Even after long-term entecavir treatment,15.4%(40/260)of CHB patients with HBV DNA<100 IU/mL still had LLV.In clinical practice,poor compliance,positive HBeAg and high viral load are risk factors for LLV.