HBV DNA低水平患者肝组织炎症活动度和纤维化程度的影响因素分析

Influencing factors for liver inflammation grade and fibrosis degree in patients with low-level HBV DNA

目的分析HBV DNA低水平患者肝组织病理特征及相关因素,为HBV DNA低水平患者的病情判断提供依据。方法选取2014年1月-2017年12月于云南省昆明市第三人民医院就诊的HBV DNA> 20 IU/ml且<2000 IU/ml者137例,对患者肝组织行病理检查,炎症分级:G1 44例,G2 84例,G3 9例;纤维化分期:S0 2例,S1 67例,S2 56例,S3 9例,S4 3例。分析患者肝组织炎症和纤维化程度与年龄、性别、感染HBV时间、血生化、HBsAg水平、HBV DNA等的关系。计量资料多组间比较采用Kruskal Wallis H检验,计数资料组间比较采用χ~2检验,使用单因素和多因素单向非条件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 G1、G2、G3 3组间HBsAg、PLT、脾静脉内径和脾脏厚度比较,差异均有统计学意义(H值分别为7. 135、7.458、7. 588、10. 150,P值均<0. 05); S0、S1、S2、S3、S4 5组间HBsAg、PLT、门静脉内径、脾静脉内径和脾脏厚度比较,差异均有统计学意义(H值分别为20. 564、12. 065、26. 171、14. 720、13. 725,P值均<0. 05)。137例患者无或轻度炎症坏死44例(<G2组),中重度炎症坏死93例(≥G2组),将单因素logistic回归分析有意义的年龄、ALT、ALP、WBC、脾静脉内径和脾脏厚度(检验水平调为0.15)纳入多因素分析显示年龄[比值比(OR)=1. 045)]、ALP(OR=1. 019)和脾脏厚度(OR=1. 150)是低水平HBV DNA者肝组织炎症≥G2的独立危险因素(P值均<0. 05)。137例患者无或轻度肝纤维化69例(<S2组),中重度肝纤维化68(≥S2组),将单因素logistic回归分析有意义的TBil、HBsAg、PLT和门静脉内径(检验水平调为0. 15)纳入多因素分析显示HBsAg(OR=2. 065)、PLT(OR=0. 988)和门静脉宽度(OR=2. 464)是低水平HBV DNA者肝组织纤维化≥S2的独立影响因素。结论绝大多数HBV DNA低水平患者均有抗病毒治疗指征,年龄、ALP和脾脏厚度与低水平HBV DNA者肝组织炎症程度密切相关; HBsAg、PLT和门静脉宽度与低水平HBV DNA者肝组织纤维化程度密切相关。

Objective To investigate liver pathological features and related factors in patients with low-level HBV DNA,and to provide a basis for evaluating the conditions of such patients. Methods A total of 137 patients with an HBV DNA level of <2000 IU/ml and >20 IU/ml who attended The Third People′s Hospital of Kunming from January 2014 to December 2017 were enrolled. Liver pathological examination was performed for all patients. Of all patients,44 had grade 1 (G1) liver inflammation,84 had grade 2 (G2) liver inflammation,and 9 had grade 3 (G3) liver inflammation;as for fibrosis stage,2 had S0 fibrosis,67 had S1 fibrosis,56 had S2 fibrosis,9 had S3 fibrosis,and 3 had S4 fibrosis. The correlation of liver inflammation grade and fibrosis stage with age,sex,duration of HBV infection,blood biochemistry,HBsAg level,and HBV DNA was analyzed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups,the chi-square test was used for comparison of categorical data between groups,and univariate and multivariate one-way non-conditional logistic regression analyses were used to investigate the influencing factors for ≥G2 liver inflammation and ≥S2 fibrosis. Results There were significant differences in HBsAg,platelet count (PLT),diameter of the splenic vein,and spleen thickness between the G1,G2,and G3 groups (H =7.135,7.458,7.588,and 10.150,all P <0.05),and there were also significant differences in HBsAg,PLT,diameter of the portal vein,diameter of the splenic vein,and spleen thickness between the S0,S1,S2,S3,and S4 groups (H =20.564, 12.065,26.171,14.720,and 13.725,all P <0.05). Of all 137 patients,44 had no or mild inflammation and necrosis (<G2 group) and 93 had moderate or severe inflammation and necrosis (≥G2 group);age,alanine aminotransferase,alkaline phosphatase (ALP),white blood cell count,diameter of the splenic vein,and spleen thickness,with statistical significance determined by the univariate logistic regression analysis,were included in the multivariate analysis (α=0.15),and the results showed that age (odds ratio [OR]=1.045, P <0.05),ALP(OR=1.019, P <0.05),and spleen thickness (OR=1.150, P <0.05) were independent risk factors for ≥G2 liver inflammation in the patients with low-level HBV DNA. Of all 137 patients,69 had no or mild liver fibrosis (<S2 group) and 68 had moderate or severe liver fibrosis (≥S2 group);total bilirubin,HBsAg,PLT,and diameter of the portal vein,with statistical significance determined by the univariate logistic regression analysis,were included in the multivariate analysis (α=0.15),and the results showed that HBsAg (OR=2.065), PLT(OR=0.988),and diameter of the portal vein (OR=2.464) were independent risk factors for ≥S2 liver fibrosis in the patients with low-level HBV DNA. Conclusion The majority of patients with low-level HBV DNA have the indication of antiviral therapy. Age,ALP,and spleen thickness are closely associated with liver inflammation grade in patients with low-level HBV DNA,and HBsAg,PLT,and diameter of the portal vein are closely associated with liver fibrosis.