长期恩替卡韦经治慢性乙型肝炎患者低病毒血症的相关影响因素
DOI: 10.3969/j.issn.1001-5256.2021.03.011
Influencing factors for low-level viremia in chronic hepatitis B patients treated with long-term entecavir antiviral therapy
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摘要:
目的 探讨长期接受恩替卡韦治疗的慢性乙型肝炎(CHB)患者仍维持低水平病毒复制的相关影响因素。 方法 选取2018年11月—2020年6月于徐州医科大学附属医院门诊接受恩替卡韦抗病毒治疗至少1年的CHB患者,根据至观察期结束患者HBV DNA载量分为低病毒血症(LLV)组和持续病毒学应答(SVR)组。观察患者人口学特征参数和实验室检测指标。计量资料两组间比较采用独立样本t检验或Mann-Whitney U检验;计数资料两组间比较采用χ2检验。采用多因素logistic回归分析长期恩替卡韦经治患者出现LLV的影响因素。 结果 共纳入560例CHB患者,其中LLV组204例,SVR组356例。两组患者比较,年龄(Z=-3.530,P<0.001)、性别(χ2=4.270,P=0.039)、是否存在肝硬化(χ2=53.879,P<0.001)、服药依从性(χ2=5.326,P=0.021)、HBeAg阳性率(χ2 =90.681,P<0.001)、治疗前基线HBV DNA载量(Z=-8.337,P<0.001)、基线HBsAg定量(Z=-10.472,P<0.001)以及用药类型(χ2=7.558,P=0.006)差异均有统计学意义。多因素logistic回归分析显示,治疗前基线HBeAg状态(OR=3.381,95%CI:1.985~5.756,P<0.001)、HBV DNA载量(OR=1.223,95%CI:1.050~1.424,P=0.010)和HBsAg定量(OR=2.448,95%CI:1.743~3.438,P<0.001)是长期恩替卡韦抗病毒治疗出现LLV的危险因素。 结论 在临床实践中,基线高载量HBV DNA水平、高HBsAg定量和HBeAg阳性的CHB患者即使长期坚持服用恩替卡韦抗病毒治疗,也存在较高的LLV风险。因此,对于此类人群应予以重视,需动态监测HBsAg定量、HBV DNA载量、HBeAg状态。 Abstract:Objective To investigate the influencing factors for persistent low-level viremia (LLV) in chronic hepatitis B(CHB) patients receiving long-term entecavir antiviral therapy. Methods The CHB patients who received entecavir antiviral therapy for at least one year in The Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were enrolled as subjects, and according to HBV DNA load at the end of the observation period, the patients were divided into LLV group and sustained virological response (SVR) group. Demographic features and laboratory markers were observed for all patients. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to investigate the influencing factors for LLV in patients receiving long-term entecavir treatment. Results A total of 560 CHB patients were enrolled, with 204 in the LLV group and 356 in the SVR group. There were significant differences between the two groups in age (Z=-3.530, P < 0.001), sex (χ2=4.270, P=0.039), presence or absence of liver cirrhosis (χ2=53.879, P < 0.001), medication compliance (χ2=5.326, P=0.021), HBeAg positive rate (χ2=90.681, P < 0.001), baseline HBV DNA load before treatment (Z=-8.337, P < 0.001), baseline HBsAg quantification (Z=-10.472, P < 0.001), and medication type (χ2=7.558, P=0.006). The multivariate logistic regression analysis showed that baseline HBeAg status before treatment (odds ratio [OR]=3.381, 95% confidence interval [CI]: 1.985-5.756, P < 0.001), HBV DNA load before treatment (OR=1.223, 95%CI: 1.050-1.424, P=0.010), and HBsAg quantification before treatment (OR=2.448, 95%CI: 1.743-3.438, P < 0.001) were risk factors for LLV in long-term entecavir antiviral therapy. Conclusion In clinical practice, CHB patients with high HBV DNA load, high HBsAg quantification, and positive HBeAg tend to have a high risk of LLV even after long-term entecavir antiviral therapy. Therefore, such population should be taken seriously with the dynamic monitoring of HBsAg quantification, HBV DNA load, and HBeAg status. -
Key words:
- Hepatitis B, Chronic /
- Low-Level Viremia /
- Entecavir /
- Risk Factors
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表 1 纳入CHB患者基线资料
指标 所有患者 (n=560) SVR组 (n=356) LLV组 (n=204) 统计值 P值 年龄(岁) 45(36~52) 47(37~53) 42(33~48) Z=-3.530 <0.001 男性[例(%)] 399(71.3) 243(68.3) 156(76.5) χ2=4.270 0.039 BMI(kg/m2) 23.95±3.37 23.87±3.39 24.10±3.35 t=-0.797 0.426 肝硬化[例(%)] 231(41.3) 188(52.8) 43(21.1) χ2=53.879 <0.001 家族史[例(%)] 213(38.0) 128(36.0) 85(41.7) χ2=1.795 0.180 良好服药依从性[例(%)] 507(90.5) 330(92.7) 177(86.8) χ2=5.326 0.021 糖尿病[例(%)] 28(5.0) 18(5.1) 10(4.9) χ2=0.006 0.936 HBeAg阳性[例(%)] 350(62.5) 170(47.8) 180(88.2) χ2=90.681 <0.001 HBV DNA(log10 IU/ml) 6.17(5.01~7.41) 5.75(4.39~6.97) 7.08(6.00~7.87) Z=-8.337 <0.001 HBsAg(log10 IU/ml) 3.47(2.99~3.92) 3.21(2.76~3.69) 3.90(3.37~4.44) Z=-10.472 <0.001 AST(U/L) 56.00(36.00~89.75) 56.00(35.00~92.50) 56.00(38.25~88.75) Z=-0.274 0.784 ALT(U/L) 73.00(45.00~123.75) 68.50(43.00~128.85) 78.00(48.25~117.50) Z=-0.691 0.489 用药类型[例(%)] χ2=7.558 0.006 恩替卡韦初治 517(92.3) 337(94.7) 180(88.2) 转换至恩替卡韦 43(7.7) 19(5.3) 24(11.8) 表 2 恩替卡韦经治CHB患者低病毒血症的多因素logistic回归分析
变量 B值 SE Wald OR 95%CI P值 年龄 -0.001 0.010 0.003 0.999 0.981~1.019 0.957 男性 0.376 0.236 2.527 1.456 0.916~2.314 0.112 肝硬化 -0.469 0.250 3.503 0.626 0.383~1.022 0.061 良好的依从性 -0.504 0.352 2.048 0.604 0.303~1.205 0.152 HBeAg阳性 1.218 0.272 20.122 3.381 1.985~5.756 <0.001 HBV DNA 0.201 0.078 6.719 1.223 1.050~1.424 0.010 HBsAg 0.895 0.173 26.695 2.448 1.743~3.438 <0.001 用药类型 0.390 0.379 1.061 1.478 0.703~3.107 0.303 -
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