HBV前C、C、BCP区位点变异与中医证型的相关性分析

目的探讨慢性乙型肝炎(CHB)患者HBV的前C区、C区、基本核心启动子(BCP)区位点变异与中医证型的相关性。方法回顾性分析2014年11月—2018年6月于河南中医药大学第一附属医院脾胃肝胆科门诊及病房诊治的CHB患者临床资料。收集并记录患者的基本情况、HBV血清学指标、HBV各位点变异情况及中医四诊信息,参照病毒性肝炎的中医辨证标准,对各病例进行辨证分型,继而分析HBV前C、C、BCP区位点变异与中医证型的相关性。计数资料组间比较采用χ²检验;计量资料多组之间及两两比较采用Kruskal-Wallis H检验。结果纳入235例CHB患者中,湿热内结证101例,肝郁脾虚证88例,瘀血阻络证17例,肝肾阴虚证19例,脾肾阳虚证10例。性别、年龄、病程在不同中医证型中存在显著差异(χ²=17.389、H=173.280、H=86.520,P值均<0.01)。CHB患者年龄在HBV前C、C、BCP区位点变异间差异有统计学意义(H=30.150,P<0.001)。HBV前C、C、BCP区变异的CHB患者其中医证型分布存在显著差异(χ²=58.117,P<0.001),主要证型为湿热内结证和肝郁脾虚证,两证型所占比例为80.43%。湿热内结证易出现A1762T、G1764A位点变异,肝郁脾虚证易出现G1896A、A1762T、G1764A位点变异,瘀血阻络证和肝肾阴虚证均易出现G1764A位点变异,脾肾阳虚证易出现I97L位点变异。结论CHB患者HBV前C、C、BCP区位点变异与中医证型存在一定的关联性,湿热内结证及肝郁脾虚证最常见,脾肾阳虚证易发生I97L位点变异。

Association of gene mutations in the pre-C,C,and basic core promoter regions of hepatitis B virus with traditional Chinese medicine syndrome types

Objective To investigate the association of gene mutations in the pre-C,C,and basic core promoter(BCP)regions of hepatitis B virus(HBV)with traditional Chinese medicine(TCM)syndrome types in patients with chronic hepatitis B(CHB).Methods A retrospective analysis was performed for the clinical data of CHB patients who were diagnosed and treated at the outpatient service and ward of Spleen,Stomach,and Hepatobiliary Department,The First Affiliated Hospital of Henan University of Chinese Medicine,from November 2014 to June 2018.Related clinical data were collected and recorded,including general information,HBV serological markers,HBV gene mutations,and information obtained by four TCM diagnostic methods.Syndrome differentiation and typing were performed for each patient with reference to the criteria for TCM syndrome differentiation of viral hepatitis,and the association of gene mutation in the pre-C,C,and BCP regions of HBV with TCM syndrome types was analyzed.The chi-square test was used for comparison of categorical data between groups,and the Kruskal-Wallis H test was used for comparison of continuous data between multiple or two groups.Results A total of 235 patients with CHB were enrolled,among whom 101 had internal retention of damp-heat,88 had stagnation of liver Qi and spleen deficiency,17 had blood stasis obstructing the collaterals,19 had liver-kidney Yin deficiency,and 10 had spleen-kidney Yang deficiency.There were significant differences in sex,age,and course of disease between the patients with different TCM syndrome types(χ²=17.389,H=173.280,H=86.520,all P<0.01),and there was a significant difference in age between the CHB patients with gene mutations in the pre-C,C and BCP regions of HBV(H=30.150,P<0.001).There was a significant difference in the distribution of TCM syndrome types between the CHB patients with gene mutations in the pre-C,C and BCP regions of HBV(χ²=58.117,P<0.001),and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency were major TCM syndrome types accounting for 80.43%.The patients with internal retention of damp-heat tended to have A1762T and G1764A mutations,and those with stagnation of liver Qi and spleen deficiency tended to have G1896A,A1762T,and G1764A mutations;G1764A mutation was often observed in the patients with blood stasis obstructing the collaterals or liver-kidney Yin deficiency,and I97L mutation was often observed in the patients with spleen-kidney Yang deficiency.Conclusion Gene mutations in the pre-C,C,and BCP regions of HBV are associated with TCM syndrome types in CHB patients,and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency are the most common TCM syndrome types.I97L mutation is often observed in patients with spleen-kidney Yang deficiency.