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目的:了解HBV相关慢加急性肝衰竭（HBV-ACLF）患者的病毒S基因准种变异特征，探讨HBV-ACLF可能的发生机制。方法:将2016年1月至2018年10月高州市人民医院收治的HBV-ACLF患者和慢性乙型肝炎（CHB）患者纳入研究，收集患者基本资料以及治疗前血清样本。提取HBV DNA，巢式PCR法扩增HBV S基因，参照相应基因型标准序列，分析两组患者的HBV S基因的准种异质性差异，包括信息熵(Sn)、平均遗传距离(d*)、同义替换率（dS）、非同义替换率（dN）指标。结果:成功扩增HBV S基因的患者共99例，其中HBV-ACLF患者56例，CHB患者43例。HBV S基因准种异质性分析显示，HBV-ACLF组的Sn(核苷酸、氨基酸)、dS、dN分别为(0.716±0.181) nt、(0.598±0.218) AA、8.259±2.607和7.103±3.081，均高于CHB组，差异均有统计学意义(n t=2.579、2.546、8.232和5.297, n P均<0.05)。S基因MHR区准种变异性分析结果显示，HBV-ACLF组的Sn(核苷酸、氨基酸)、d*(核苷酸、氨基酸)、dS、dN分别为(0.756±0.184) nt、(0.613±0.229) AA、(7.137±3.074) nt、(8.280±3.194) AA、9.091±2.720和7.429±2.860，明显高于CHB组，差异均有统计学意义(n t=5.332,、5.020、3.599、5.772、4.093和3.857，n P均<0.01)。n 结论:HBV-ACLF患者更易发生S基因变异，尤其是MHR区变异，可能与HBV-ACLF产生相关。“,”Objective:To understand the quasispecies variation of S gene in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) , so as to explore the possible mechanism of HBV-ACLF.Methods:Patients with HBV infection in Gaozhou People's Hospital from January 2016 to October 2018 were enrolled and divided into HBV-ACLF group and chronic hepatitis B (CHB) group. The clinical data and blood samples before treatment were collected. HBV DNA in serum was extracted, and HBV S region was amplified by nest-PCR. According to the genotypic standard sequence, the quasispecies heterogeneity of HBV S gene including Shannon entropy (Sn) , average genetic distance (d*) , synonymous substitution rate (dS) and non-synonymous substitution rate (dN) was analyzed between the two groups.Results:HBV S region was successfully amplified from 99 patients, including 56 cases in HBV-ACLF group and 43 cases in CHB group. The quasispecies heterogeneity of S gene showed that the Sn (nucleotide and amino acid) , dS and dN in HBV-ACLF group were (0.716±0.181) nt, (0.598±0.218) AA, 8.259±2.607 and 7.103±3.081, which were all significantly higher than those in CHB group (n t=2.579, 2.546, 8.232 and 5.297, n P all <0.05) . The quasispecies heterogeneity of major hydrophilic region (MHR) in S gene showed that the Sn (nucleotide and amino acid) , d* (nucleotide and amino acid) , dS and dN in HBV-ACLF group were (0.756±0.184) nt, (0.613±0.229) AA, (7.137±3.074) nt, (8.280±3.194) AA, 9.091±2.720 and 7.429±2.860, which were all significantly higher than those in CHB group ( n t=5.332n , 5.020n , 3.599n , 5.772n , 4.093 and 3.857, n P all <0.01) .n Conclusions:The S gene variation occurs more frequently in patients with HBV-ACLF, especially the MHRvariation which may be related to HBV-ACLF.