HBV感染免疫耐受期肝组织炎症和纤维化的影响因素分析

Influencing factors for liver inflammation and fibrosis in the immune-tolerant phase of HBV infection

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。

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.