HBV突变与HBV相关慢加急性肝衰竭相关性研究

Association between HBV mutations and HBV-related acute-on-chronic liver failure

目的探讨HBV突变与慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)之间的相关性。方法以87例HBV相关ACLF患者为研究对象,另选取52例慢性乙型肝炎(chronic hepatitis B,CHB)患者和51例HBV肝硬化(liver cirrhosis,LC)患者为对照,应用聚合酶链反应及基因测序对患者血清标本进行HBV基本核心启动子区、前C区和C区13个位点的突变检测,分析HBV突变与ACLF发生的相关性。结果 CHB、LC、ACLF组人均核苷酸变异检出位点分别为2.31、3.55和3.86个。nt1762、nt1846、nt1899和nt1913 4个突变位点的核苷酸突变率比较,ACLF组高于CHB组;nt1764位点突变率组间比较LC组高于ACLF组,而nt1846和nt1913位点突变率比较LC组低于ACLF组;nt1753、nt1762、nt1764和nt1899 4个突变位点的核苷酸突变率比较,LC组高于CHB组。多因素分析提示A1846T和C1913(A/G)核苷酸突变是预测ACLF的有效指标。结论 CHB或LC患者HBV基因序列的A1846T和C1913(A/G)核苷酸突变可能与其发生ACLF密切相关。

Objective To investigate the association between HBV mutations and the development of acute-on-chronic liver failure （ACLF） in patients with chronic HBV infection. Methods A total of 87 HBV-related ACLF （HBV-ACLF） patients were enrolled in the study, and 52 age-and sex-matched patients with chronic hepatitis B （CHB） and 51 patients with liver cirrhosis （LC） were selected as controls. The mutations at HBV basic core promoter, pre-core, and partial C regions were determined by nest-ed PCR and direct sequencing methods. The association between HBV mutations and the development of ACLF was analyzed. Results The average numbers of mutations in CHB, LC and ACLF groups were 2.31, 3.55 and 3.86, respectively. As compared with CHB group, ACLF group had more mutations at nt1762, nt1846, nt1899 and nt1913; as compared with LC group, ACLF had fewer mutations at nt1764, and more mutations at nt1846 and nt1913; as compared with CHB group, LC group had more mutations at nt1753, nt1762, nt1764 and nt1899. Multivariable analysis indicated that A1846T and C1913（A/G） mutations were independent fac-tors for ACLF. Conclusion HBV nucleotide mutations of A1846T and C1913（A/G） may be closely associated with the development of ACLF.