IL-6基因多态性对HBV相关ACLF患者短期预后的影响

doi:10.3969/j.issn.1672-5069.2021.04.016

摘要/Abstract

摘要： 目的研究白细胞介素6(IL-6)单核苷酸多态性(SNP)对慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者短期预后的影响。方法 2017年4月～2020年4月我院收治的HBV-ACLF患者134例,采用imLDR^TM多重SNP分型试剂盒检测血清IL-6基因rs1524107、rs2069837、rs2069840和rs2069845共4个位点的SNP分型,应用Gene Mapper 4.1软件进行原始数据的分析。结果在本组134例ACLF患者中,90 d生存99例(73.9%),死亡35例;死亡组血清总胆红素水平为(399.3±168.8)μmol/L,显著高于生存组【(285.9±121.5)μmol/L,P＜0.05】,凝血酶原时间国际标准化比值为(2.3±0.8),显著高于生存组【(1.7±0.4),P＜0.05】,而两组血清白蛋白、肌酐、降钙素原、白细胞计数和血小板计数比较差异无统计学意义(P＞0.05);IL-6基因rs1524107、rs2069837、rs2069840和rs2069845位点分布情况均符合Hardy-Weinberg遗传平衡定律(P＞0.05),具有群体代表性;两组IL-6基因rs1524107、rs2069837、rs2069840和rs2069845位点基因型频数分布比较差异无统计学意义(P＞0.05),两组IL-6基因rs1524107、rs2069837、rs2069840和rs2069845位点等位基因频数分布比较差异也无统计学意义(P＞0.05)。结论在HBV-ACLF生存与死亡患者,血清IL-6基因位点SNP分布无显著性差异,因此该检测不能预测患者预后,可根据其他常用的指标预测。

关键词: 慢加急性肝衰竭, 乙型肝炎, 白细胞介素6, 单核苷酸多态性, 预后

Abstract: Objective The aim of this study was to investigate the implication of interleukin-6 (IL-6) gene polymorphism in short-term prognosis of patients with hepatitis B-inducedacute-on-chronic liver failure (HBV-ACLF). Methods 134 patients with HBV-ACLF were admitted to our hospital between April 2017 and April 2020. The single nucleotide polymorphisms (SNPs) of rs1524107, rs2069837, rs2069840 and rs2069845 of IL-6 gene were detected by imLDRTM multiple SNP typing kit. Results Out of the 134 patients with HBV-ACLF, the 90 day survivalrate was 73.9% with 35 dead; the peak total serum bilirubin level and prothrombin time international standardized ratio in dead patients were(399.3±168.8)μmol/L and (2.3±0.8), both significantly higher than[(285.9±121.5)μmol/L and (1.7±0.4), respectively, P＜0.05] in survived patients, while there were no significant differences as respect toserum albumin, creatinine, procalcitonin, white blood cell counts and platelet counts (P＞0.05); the distributions of rs1524107, rs2069837, rs2069840 and rs2069845 conform to Hardy-Weinberg genetic equilibrium law (P>0.05), and possess population representative; the genotype frequency distribution of rs1524107, rs2069837, rs2069840 and rs2069845 in the two groups showed no statistically significant difference (P>0.05), and the allele frequency distribution of rs1524107, rs2069837, rs2069840 and rs2069845 in the two groups also showed no statistical significance (P>0.05). Conclusion The SNPs of IL-6 rs1524107, RS2069837, rs2069840 and RS2069845 in survived and dead patients with HBV-ACLF have no significant differences, so the detection could not predict the prognosis of patients in this setting and might deal with them routinely.

Key words: Acute-on-chronic liver failure, Hepatitis B, Interleukin6, Single nucleotide polymorphism, Prognosis

鲁小龙, 解春宝. IL-6基因多态性对HBV相关ACLF患者短期预后的影响[J]. 实用肝脏病杂志, 2021, 24(4): 516-519.

Lu Xiaolong, Xie Chunbao. Implication of IL-6 gene polymorphism in short-term prognosis of patients with hepatitis B-induced acute-on-chronic liver failure[J]. Journal of Practical Hepatology, 2021, 24(4): 516-519.

参考文献

[1] Chen T, Yang Z, Choudhury AK, et al. Complications constitute a major risk factor for mortality in hepatitis B virus-related acute-on-chronic liver failure patients: a multi-national study from the Asia-Pacific region. Hepatol Int, 2019, 13(6):695-705.
[2] Lei Q, Zhang Y, Ke C, et al. Value of the albuminbilirubin score in the evaluation of hepatitis B virusrelated acuteonchronic liver failure, liver cirrhosis, and hepatocellular carcinoma. Exp Ther Med, 2018, 15(3):3074-3079.
[3] Wu D, Sun Z, Liu X, et al. HINT: a novel prognostic model for patients with hepatitis B virus-related acute-on-chronic liver failure. Aliment Pharmacol Ther, 2018, 48(7):750-760.
[4] Fischer J, Silva TE, Soares ESPE, et al. From stable disease to acute-on-chronic liver failure: circulating cytokines are related to prognosis in different stages of cirrhosis. Cytokine, 2017, 91(1):162-169.
[5] Kim HY, Jhun JY, Cho ML, et al. Interleukin-6 upregulates Th17 response via mTOR/STAT3 pathway in acute-on-chronic hepatitis B liver failure. J Gastroenterol, 2014, 49(8):1264-1273.
[6] 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2012年版). 实用肝脏病杂志, 2013, 16(3):210-216.
[7] 李海. CATCH-LIFE中国多中心研究对慢加急性肝衰竭前期概念验证和新思路. 中华肝脏病杂志, 2020, 28(4):307-309.
[8] 李子月, 杨士田, 吴玲玲, 等. 乙型肝炎病毒相关慢加急性肝衰竭患者预后危险因素分析及预后模型建立. 中华传染病杂志, 2019, 37(12):737-741.
[9] 林苏, 周卿, 林烨鸿, 等. 白细胞介素-22基因多态性与乙型肝炎病毒相关性慢加急性(亚急性)肝功能衰竭的预后分析. 中华传染病杂志, 2018, 36(12):730-735.
[10] Wu T, Li J, Shao L, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut, 2018, 67(12):2181-2191.
[11] Chen W, You J, Chen J, et al. Modified model for end-stage liver disease improves short-term prognosis of hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol, 2017, 23(40):7303-7309.
[12] Jiang QQ, Han MF, Ma K, et al. Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis. World J Gastroenterol, 2018, 24(21):2300-2310.
[13] Xiang X, Feng D, Hwang S, et al. Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming of impaired regeneration pathways in mice. J Hepatol, 2020, 72(4):736-745.
[14] Ariza X, Graupera I, Coll M, et al. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. J Hepatol, 2016, 65(1):57-65.
[15] Karatayli E, Hall RA, Weber SN, et al. Effect of alcohol on the interleukin 6-mediated inflammatory response in a new mouse model of acute-on-chronic liver injury. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(2):298-307.
[16] Alcaraz-Quiles J, Titos E, Casulleras M, et al. Polymorphisms in the IL-1 gene cluster influence systemic inflammation in patients at risk for acute-on-chronic liver failure. Hepatology, 2017, 65(1):202-216.
[17] El-Maadawy EA, Talaat RM, Ahmed MM, et al. Interleukin-6 promotor gene polymorphisms and susceptibility to chronic hepatitis B virus in egyptians. HumImmunol, 2019, 80(3):208-214.
[18] Attar M, Azar SS, Shahbazi M. Interleukin-6-174 promoter polymorphism and susceptibility to hepatitis B virus infection as a risk factor for hepatocellular carcinoma in Iran. Asian Pac J Cancer Prev, 2016, 17(5):2395-2399.
[19] 朱秀云, 汪文斐, 吴伟刚, 等. IL-6基因单核苷酸多态性与中国汉族人群乙型肝炎易感性的相关性研究. 中华实验和临床病毒学杂志, 2017, 31(5):397-400.