外周血HLA-DRB1基因多态性对慢性乙型肝炎进展至肝细胞癌的影响

Influence of HLA-DRB1 gene polymorphism on hepatitis B virus-related hepatocellular carcinoma

目的比较慢性乙型肝炎与慢性乙型肝炎进展至肝细胞癌患者外周血HLA-DRB1等位基因表达变化,探讨HLA-DRB1基因多态性对慢性乙型肝炎进展为肝细胞癌的影响。方法2020年11月—2022年10月山西医科大学第一医院诊治慢性乙型肝炎进展至肝细胞癌患者126例为肝细胞癌组,同期诊治慢性乙型肝炎患者108例为乙型肝炎组。采用序列特异性引物PCR法检测2组外周血HLA-DRB1基因多态性,共检出26个HLA-DRB1等位基因片段,其中14个等位基因阳性比率>2.0%。比较2组男性、年龄>65岁、合并高血压及糖尿病、乙型肝炎病毒(HBV)感染>10年、HBV-DNA载量>10^(4)、未行抗HBV治疗、乙型肝炎表面抗原阳性及HLA-DRB1等位基因阳性率;多因素logistic回归分析慢性乙型肝炎进展至肝细胞癌的HLA-DRB1等位基因。结果肝细胞癌组年龄>65岁(38.1%)、HBV感染>10年(52.4%)、未行抗HBV治疗(57.1%)比率均高于乙型肝炎组(25.9%、38.9%、43.5%)(χ^(2)=3.927,P=0.048;χ^(2)=4.260,P=0.039;χ^(2)=4.319,P=0.038),男性、合并高血压及糖尿病、HBV-DNA载量>104、乙型肝炎表面抗原阳性比率与乙型肝炎组比较差异均无统计学意义(P>0.05)。肝细胞癌组HLA-DRB1等位基因DRB1*0401阳性率(4.0%)低于乙型肝炎组(11.1%)(χ^(2)=3.792,P=0.052),DRB1*0803(17.5%)、DRB1*1501(29.4%)阳性率高于乙型肝炎组(5.6%、11.1%)(χ^(2)=6.220,P=0.013;χ^(2)=7.786,P=0.005),DRB1*0405、DRB1*0701、DRB1*0901、DRB1*1001、DRB1*1101、DRB1*1104、DRB1*1201、DRB1*1202、DRB1*1405、DRB1*1454、DRB1*1502阳性率与乙型肝炎组比较差异均无统计学意义(P>0.05)。HLA-DRB1等位基因DRB1*0803(OR=4.661,95%CI:1.749~12.424,P=0.002)、DRB1*1501(OR=3.565,95%CI:1.723~7.374,P=0.001)是慢性乙型肝炎进展为肝细胞癌的HLA-DRB1等位基因。结论年龄>65岁、HBV感染>10年,未行抗HBV治疗的慢性乙型肝炎患者易进展为肝细胞癌,DRB1*0803、DRB1*1501是慢性乙型肝炎进展为肝细胞癌的HLA-DRB1等位基因。

Objective To observe the changes of HLA-DRB1 alleles in patients with chronic hepatitis B and hepatitis B virus-related hepatocellular carcinoma(HBV-related HCC),and to explore the influence of HLA-DRB1 gene polymorphism on HCC in patients with hepatitis B.Methods From November 2020 to October 2022,126 patients with HBV-related HCC(HCC group)were diagnosed and treated in the First Hospital of Shanxi Medical University,and another 108 patients with chronic hepatitis B(CHB)were as CHB group.The HLA-DRB1 gene polymorphisms in peripheral blood were detected by sequence-specific primers PCR in two groups,and 26 HLA-DRB1 alleles were detected,of which 14 positive alleles accounted for more than 2.0%,The percentages of male patients and patients with age>65 years,hypertension,diabetes,HBV infection>10 years,HBV-DNA load >10^(4),receiving no anti-HBV therapy,hepatitis B surface antigen-positive and HLA-DRB1 allele-positive were compared between two groups.Multivariate logistic regression analysis was performed to evaluate the HLA-DRB1 alleles of HBV-related HCC.Results The percentages of patients with age>65 years,HBV infection10 years and receiving no anti-HBV therapy were higher in HCC group(38.1%,52.4%,57.1%)than those in CHB group(25.9%,38.9%,43.5%)(χ^(2)=3.927,P=0.048;χ^(2)=4.260,P=0.039;χ^(2)=4.319,P=0.038),and there were no significant differences in the percentages of male patients and patients with hypertension,diabetes,HBV-DNA load10~4 and hepatitis B surface antigen positive between two groups(P>0.05),The positive rate of HLA-DRB1*0401 allele was lower in HCC group(4.0%)than that in CHB group(11.1%)(χ^(2)=3.792,P=0.052),the positive rates of DRB1*0803 and DRB1*1501were higher in HCC group(17.5%,29.4%)than those in CHB group(5.6%,11.1%)(χ^(2)=6.220,P=0.013;χ^(2)=7.786,P=0.005),and there were no significant differences in the positive rates of DRB1*0405,DRB1*0701,DRB1*0901,DRB1*1001,DRB1*1101,DRB1*1104,DRB1*1201,DRB1*1202,DRB1*1405,DRB1*1454,and DRB1*1502 between two groups(P>0.05),DRB1*0803(OR=4.661,95%CI:1.749-12.424,P=0.002)and DRB1*1501(OR=3.565,95%CI:1.723-7.374,P=0.001)were the HLA-DRB1 alleles of HVB-related HCC.Conclusion The patients with age>65 years,HBV infection>10 years,and receiving no anti-HBV therapy are prone to develop HCC,and HLA-DRB1*0803 and HLA-DRB1*1501 are the HLA-DRB1 alleles of HVB-related HCC.