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HBV感染免疫耐受期肝组织炎症和纤维化的影响因素分析
DOI: 10.3969/j.issn.1001-5256.2022.09.012
伦理学声明：本研究方案于2015年1月1日经由昆明市第三人民医院伦理委员会审批，批号：昆三医伦2018030709，患者及家属均签署知情同意书。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：刘春云负责资料收集、分析，撰写论文；常丽仙、李俊义、祁燕伟、李卫昆、李惠敏、张映媛负责资料收集; 刘立、高建鹏负责资料分析，指导写作思路并最后定稿。
Influencing factors for liver inflammation and fibrosis in the immune-tolerant phase of HBV infection
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摘要:
目的 对慢性HBV感染免疫耐受期患者进行肝脏损伤程度及肝纤维化的评价，为免疫耐受期患者的病情判断提供依据。 方法 随机选取昆明市第三人民医院2015年1月—2019年12月HBV DNA水平≥107 IU/mL、ALT≤40 U/L且临床资料完整者300例，收集其年龄、性别、感染HBV时间、血生化、HBsAg、HBV DNA等资料，并对患者的肝组织行病理检查，根据炎症分级分为两组(G＜2组和G≥2组)，根据纤维化程度分为两组(S＜2组和S≥2组)。计量资料2组间比较采用t检验，使用单因素和多因素非条件logistic回归分析肝组织病理炎症活动≥G2和纤维化程度≥S2的影响因素。 结果 300例患者中，G≥2组213例(71%)，S≥2组120例(40%)，基线年龄(26.06±9.01)岁，男性占48%，感染时间(5.62±5.09)年。单因素分析显示，G＜2组和G≥2组ALT、ALP、Alb、PLT、门静脉内径和脾脏厚度比较，差异均有统计学意义(t值分别为-26.677、-11.612、2.149、5.410、-6.092、-2.911，P值均＜0.05)；S＜2组与S≥2组比较，感染时间、ALT、ALP、Alb、HBV DNA、PLT、门静脉内径和脾脏厚度比较，差异均有统计学意义(t值分别为-6.320、-6.694、-7.880、2.349、4.552、19.160、-5.782、-5.622，P值均＜0.05)。多因素分析显示，ALT(OR=10.270，95%CI：2.212~47.672，P=0.003)、ALP(OR=1.097，95%CI：1.013~1.188，P=0.023)是免疫耐受期患者肝组织炎症≥G2的独立危险因子；ALP(OR=1.034，95%CI：1.015~1.054，P＜0.001)、PLT(OR=0.913，95%CI：0.886~0.938，P＜0.001)、HBV DNA(OR=0.198，95%CI：0.062~0.636，P=0.007)和感染时间(OR=1.176，95%CI：1.033~1.340，P=0.015)是免疫耐受期患者肝组织纤维化≥S2的独立影响因子。 结论 大多数免疫耐受期患者都有显著的肝组织学病变。ALT、ALP是免疫耐受期患者肝组织显著炎症的影响因素，ALP、HBV DNA、PLT和感染时间是免疫耐受期患者肝组织显著纤维化的影响因素。 Abstract:Objective To evaluate the degree of liver injury and liver fibrosis in patients in the immune-tolerant phase of chronic HBV infection, and to provide a basis for judging the condition of patients in the immune-tolerant phase. Methods A total of 300 patients with HBV DNA ≥107 IU/mL, alanine aminotransferase (ALT) ≤40 U/L, and complete data who were treated in The Third People's Hospital of Kunming from January 2015 to December 2019 were enrolled as subjects, and related data were collected, including age, sex, duration of HBV infection, blood biochemistry, hepatitis B surface antigen (HBsAg) level, and HBV DNA. Liver pathological examination was performed for all patients, and the patients were divided into G < 2 and G ≥2 groups according to inflammation grade and S < 2 and S ≥2 groups according to the degree of fibrosis. The t-test was used for comparison of continuous data between two groups, and univariate and multivariate unconditional logistic regression analyses were used to investigate the influencing factors for G ≥2 liver inflammation and S ≥2 liver fibrosis. Results Among the 300 patients, 213 (71%) had G ≥2 liver inflammation and 120 (40%) had S ≥2 liver fibrosis, with a baseline age of 26.06±9.01 years; male patients accounted for 48%, and the duration of infection was 5.62±5.09 years. The univariate analysis showed that there were significant differences between the G < 2 and G ≥2 groups in ALT, alkaline phosphatase (ALP), albumin (Alb), platelet count (PLT), diameter of the portal vein, and spleen thickness (t=-26.677, -11.612, 2.149, 5.410, -6.092, and -2.911, all P < 0.05), and there were significant differences between the S < 2 and S ≥2 groups in duration of infection, ALT, ALP, Alb, HBV DNA, PLT, diameter of the portal vein, and spleen thickness (t=-6.320, -6.694, -7.880, 2.349, 4.552, 19.160, -5.782, and -5.622, all P < 0.05). The multivariate analysis showed that ALT (odds ratio [OR]=10.270, 95% confidence interval [CI]: 2.212-47.672, P=0.003) and ALP (OR=1.097, 95%CI: 1.013-1.188, P=0.023) were independent risk factors for G ≥2 liver inflammation in patients in the immune-tolerant phase, and ALP (OR=1.034, 95%CI: 1.015-1.054, P < 0.001), PLT (OR=0.913, 95%CI: 0.886-0.938, P < 0.001), HBV DNA (OR=0.198, 95%CI: 0.062-0.636, P=0.007), and duration of infection (OR=1.176, 95%CI: 1.033-1.340, P=0.015) were independent influencing factors for S ≥2 liver fibrosis in patients in the immune-tolerant phase. Conclusion Most patients in the immune-tolerant phase have significant liver histological changes. ALT and ALP are the influencing factors for significant liver inflammation, and ALP, HBV-DNA, PLT, and infection time are the influencing factors for significant liver fibrosis in patients in the immune-tolerant phase. -
Key words:
- Hepatitis B virus /
- Immune Tolerance /
- Risk Factors
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表 1 300例HBV感染免疫耐受期患者一般资料
Table 1. General information of 300 patients with hepatitis B (immune-tolerant phase)
指标 数值 男/女(例) 144/156 年龄(岁) 26.06±9.01 基因型(B/C/B和C/不详) 62/221/16/1 感染时间(年) 5.62±5.09 TBil(μmol/L) 15.79±8.09 GGT(U/L) 19.51±14.80 AST(U/L) 24.19±5.90 ALT(U/L) 31.81±7.09 ALP(U/L) 134.98±58.08 Alb(g/L) 44.05±4.22 Glo(g/L) 25.69±4.10 HBsAg(lgIU/mL) 3.96±1.15 HBV DNA(lgIU/mL) 8.03±0.54 WBC(×109/L) 5.50±1.38 PLT(×109/L) 174.14±63.16 门静脉内径(mm) 11.39±1.88 脾静脉内径(mm) 5.04±0.25 脾脏厚度(mm) 30.35±4.62 肝硬度(kPa) 5.67±2.07 
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表 2 300例HBV感染免疫耐受期患者肝组织炎症分级的分布及临床特征
Table 2. Distribution and clinical characteristics of liver tissue inflammation grades in 300 patients with hepatitis B (immune-tolerant phase)
指标 G＜2组(n=87) G≥2组(n=213) t值 P值 年龄(岁) 24.92±8.41 26.53±9.22 -1.403 0.162 感染时间(年) 4.82±4.33 5.95±5.34 -1.759 0.080 TBil(μmol/L) 15.08±6.28 16.08±8.72 -0.973 0.332 GGT(U/L) 19.26±10.40 19.61±16.28 -0.183 0.855 AST(U/L) 24.23±5.59 24.17±6.03 0.075 0.941 ALT(U/L) 22.51±5.75 35.61±2.74 -26.677 ＜0.001 ALP(U/L) 84.34±37.44 155.67±52.02 -11.612 ＜0.001 Alb(g/L) 44.87±3.51 43.72±4.44 2.149 0.032 Glo(g/L) 25.97±3.81 25.57±4.21 0.780 0.436 HBV DNA(lgIU/mL) 8.08±0.56 8.01±0.53 1.091 0.276 WBC(×109/L) 5.45±1.24 5.51±1.43 -0.330 0.741 PLT(×109/L) 203.64±54.20 162.09±62.69 5.410 ＜0.001 门静脉内径(mm) 10.41±1.00 11.79±2.01 -6.092 ＜0.001 脾静脉内径(mm) 5.06±0.33 5.03±0.21 0.736 0.462 脾脏厚度(mm) 29.15±4.55 30.84±4.56 -2.911 0.004 肝硬度(kPa) 5.69±2.25 5.66±2.14 0.083 0.934
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表 3 300例HBV感染免疫耐受期患者肝组织纤维化分级的分布及临床特征
Table 3. Distribution and clinical characteristics of liver fibrosis grades in 300 patients with hepatitis B (immune-tolerant phase)
指标 S＜2组(n=180) S≥2组(n=120) t值 P值 年龄(岁) 25.64±8.96 26.68±9.07 -0.978 0.329 感染时间(年) 4.20±3.84 7.76±5.93 -6.320 ＜0.001 TBil(μmol/L) 15.60±7.00 16.08±9.51 -0.502 0.616 GGT(U/L) 20.06±17.26 18.69±10.06 0.781 0.435 AST(U/L) 23.99±5.09 24.48±6.95 -0.702 0.483 ALT(U/L) 29.72±7.78 34.94±4.34 -6.694 ＜0.001 ALP(U/L) 115.32±57.92 164.48±44.33 -7.880 ＜0.001 Alb(g/L) 44.51±3.60 43.36±4.94 2.349 0.019 Glo(g/L) 25.90±4.13 25.36±4.04 1.123 0.263 HBV DNA(lgIU/mL) 8.14±0.51 7.86±0.53 4.552 ＜0.001 WBC(×109/L) 5.51±1.34 5.48±1.43 0.151 0.880 PLT(×109/L) 212.39±53.38 116.77±14.31 19.160 ＜0.001 门静脉内径(mm) 10.91±1.41 12.13±2.24 -5.782 ＜0.001 脾静脉内径(mm) 5.03±0.23 5.05±0.27 -0.727 0.468 脾脏厚度(mm) 29.18±4.80 32.10±3.71 -5.622 ＜0.001 肝硬度(kPa) 5.80±2.25 5.48±2.04 1.221 0.223
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