Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.
目的： 探讨白细胞介素-6（IL-6）单核苷酸多态性（SNP）与乙型肝炎病毒（HBV）相关性慢加急性肝衰竭（ACLF）发生与预后的关系。 方法： 纳入2012年7月—2018年3月就诊于福建医科大学附属第一医院肝病中心诊断为HBV感染慢性肝病患者，分成HBV-ACLF组及非ACLF组。应用imLDR(TM)多重SNP分型试剂盒检测IL-6基因rs1524107、rs1800795、rs1800797、rs2069827、rs2069830、rs2069837、rs2069840及rs2069845共8个位点的SNP分型。同时回顾病例资料，随访ACLF组3个月生存情况。正态分布计量资料用x±s表示，采用t检验；非正态分布的计量资料用M（QR）表示，采用非参数检验；基因多态性与HBV-ACLF发生的相对风险度采用多元logistic回归分析,以分析IL-6 SNP与HBV-ACLF的发生与预后的关系。 结果： 共400例患者纳入研究，其中HBV-ACLF组122例（30.5%），非ACLF组278例（69.5%）。两组间总胆红素、白蛋白、白细胞计数、中性粒细胞百分比、血小板计数、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、凝血酶原时间及其国际标准化比值、肌酐、终末期肝病模型评分比差异均有统计学意义（P < 0.001）。所有研究对象的IL-6基因rs1800795、rs1800797、rs2069827、rs2069830位点的基因型未见突变或突变频率低于1%。IL-6的rs1524107、rs2069837、rs2069840、rs2069845位点基因型分布在两组间差异无统计学意义（P > 0.05），多元logistic回归模型分析显示，IL-6基因上述4个位点的SNP与HBV-ACLF发病风险无关，与HBV-ACLF 3个月预后也无显著相关性。 结论： IL-6 rs1524107、rs1800795、rs1800797、rs2069827、rs2069830、rs2069837、rs2069840、rs2069845共8个位点的SNP与HBV-ACLF发生及短期预后无关。.
Keywords: Acute-on-chronic liver failure; Hepatitis B virus; Interleukin-6; Single nucleotide polymorphism.