核苷(酸)类似物经治的慢性乙型肝炎患者发生低病毒血症影响因素分析  

Influencing factors of low level viremia in patients with chronic hepatitis B during nucleos(t)ide analogue treatment

作　　者：钱花 杨忠祥 石荔[1] Qian Hua;Yang Zhongxiang;Shi Li(Department of Infectious Diseases,Provincial People's Hospital,Xizang Autonomous Region,Lhasa 850000,China)

机构地区：[1]西藏自治区人民医院感染性疾病科,拉萨市850000

出　　处：《实用肝脏病杂志》2025年第2期186-189,共4页Journal of Practical Hepatology

基　　金：西藏自治区科技厅“中央引导地方”科研项目(编号:XZ202201YD0036C)。

摘　　要：目的探讨接受长期核苷(酸)类似物(NAs)治疗的慢性乙型肝炎(CHB)患者低病毒血症(LLV)发生率及其危险因素。方法2022年5月~2024年5月我院门诊诊治的CHB患者212例,均经规律NAs治疗超过48周。采用ELISA法检测血清HBV标记物,采用PCR法检测血清HBV DNA载量,常规检测血生化指标和血常规,计算天冬氨酸氨基转移酶/血小板比值指数(APRI)和基于4因子的肝纤维化指数(FIB-4),使用流式细胞仪检测外周血T、B、NK细胞百分比,使用Fibrotouch行肝脏硬度检测(LSM),采用多因素Logistic回归分析。结果在212例CHB患者中,LLV发生率为33.5%,完全病毒学应答(CVR)率为66.5%;LLV组基线患者年龄为(42.4±10.2)岁,显著小于CVR组【(46.4±12.0)岁,P<0.05】,有乙型肝炎家族史、合并脂肪肝、应用恩替卡韦(ETV)治疗、血清HBV DNA高载量、HBeAg阳性和血清AST低水平发生率分别为80.3%、53.5%、63.4%、83.1%、93.0%和66.2%,均显著高于CVR组(分别为41.1%、42.6%、48.9%、36.2%、44.0%和34.8%,均P<0.05);LLV组FIB-4和LSM分别为1.21(0.87,1.78)和7.2(6.4,8.1)kPa,显著大于CVR组【分别为1.76(1.23,2.44)和6.5(5.9,7.1)kPa,P<0.05】;多因素Logistic回归分析结果显示,乙肝家族史(OR=0.181,P=0.002)、HBeAg阳性(OR=3.892,P<0.001)和血清AST低水平(OR=0.269,P==0.001)均是LLV发生的危险因素;LLV组与CVR组外周血CD4^(+)和CD8^(+)细胞百分比及CD4^(+)/CD8^(+)比值无统计学差异【分别为(35.9±6.9)%、(30.8±8.6)%和(1.3±0.5)对(36.0±7.7)%、(29.1±8.1)%和(1.4±0.6),均P>0.05】。结论有乙型肝炎家族史、血清HBeAg阳性、ALT低水平和HBV DNA高载量的慢性乙型肝炎患者在NAs抗病毒治疗过程中可能发生LLV,深入研究LLV发生的原因并予以处置,对于改善预后可能有积极的意义。Objective The aim of this study was to investigate influencing factors of low level viremia(LLV)in patients with chronic hepatitis B(CHB)during nucleos(t)ide analogues(NAs)antiviral treatment.Methods A retrospective study was conducted on 212 patients with CHB between May 2022 and May 2024,and all enrolled patients had received regular NAs treatment for more than 48 weeks in our hospital.Serum HBeAg and HBV DNA loads were routinely detected.AST/platelet count ratio index(APRI)and based on four fibrosis factors(FIB-4)score were calculated.LLV was defined as serum HBV DNA loads were at range of 20 to 2000 IU/ml.Peripheral blood T cells,B cells,NK lymphocyte subsets were determined by FCA.Liver stiffness measurement(LSM)was detected by Fibrotouch.Multivariate Logistic regression analysis was applied to reveal impacting factors for LLV occurrence.Results Of 212 patients with CHB in our series,prevalence of LLV was 33.5%,with complete virological response(CVR)of 66.5%;mean age at baseline in patients with LLV was(42.4±10.2)yr,much younger than[(46.4±12.0)yr,P<0.05]in patients with CVR,percentages of hepatitis B family history,concomitant fatty liver,entevavir(ETV)antiviral treatment,high loads of serum HBV DNA,serum HBeAg positive and low serum AST level in patients with LLV were 80.3%,53.5%,63.4%,83.1%,93.0% and 66.2%,all significantly higher than 41.1%,42.6%,48.9%,36.2%,44.0% and 34.8%,respectively(all P<0.05)in patients with CVR;FIB-4 score and LSM in patients with LLV were 1.21(0.87,1.78)and 7.2(6.4,8.1)kPa,both significantly greater than[1.76(1.23,2.44)and 6.5(5.9,7.1)kPa,respectively,P<0.05]in those with CVR;multivariate Logistic regression analysis showed that hepatitis B family history(OR=0.181,P=0.002),serum HBeAg positive(OR=3.892,P<0.001)and low serum AST level(OR=0.269,P==0.001)were all the independent risk factors impacting occurrence of LLV;there were no significant differences as respect to percentages of peripheral blood CD4^(+)and CDO8^(+)cells as well as CD4^(+)/CD8^(+)cell ratio between patients w

关 键 词：慢性乙型肝炎 核苷(酸)类似物 低病毒血症 影响因素 治疗 

分 类 号：R512.62[医药卫生—内科学]