Association of N-glycosylation mutation of HBV envelope protein with the development and prognosis of acute-on-chronic liver failure in patients with chronic hepatitis B
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摘要: 目的探索HBV包膜蛋白N-糖基化修饰变异与慢性乙型肝炎患者发生慢加急性肝衰竭(ACLF)的关系。方法入选HBV-ACLF患者90例,同期60例慢性乙型肝炎作对照。套式PCR扩增患者的HBV S区序列并测序,分析HBV包膜蛋白N-糖基化情况与ACLF发生的关系,并分析ACLF疾病严重程度、90 d生存率与HBV包膜蛋白N-糖基化的关系。结果慢性乙型肝炎患者纳入分析51例(85.0%),HBV-ACLF患者纳入分析79例(87.8%)。慢性乙型肝炎患者Asn59 N-糖基化样本33例(64.7%),Asn4 N-糖基化样本21例(41.2%),高于HBV-ACLF患者的Asn59 N-糖基化样本16例(20.3%)(P<0.001)和Asn4 N-糖基化样本14例(17.7%)(P=0.003)。ACLF患者中Asn59、Asn4 N-糖基化与非糖基化患者肝功能水平、HBV DNA、MELD评分及90 d生存率差异均无统计学意义(P值均>0.05)。结论 HBV包膜蛋白变异导致的Asn59、Asn4 N-糖基化水平降低与ACLF发生可能相关。Abstract: Objective To investigate the association of N-glycosylation mutation of HBV envelope protein with the development of acute-on-chronic liver failure ( ACLF) in patients with chronic hepatitis B ( CHB) . Methods A total of 90 patients with HBV-ACLF were enrolled, and 60 patients with CHB were enrolled as control group. Nested PCR was used for the multiplication and sequencing of HBV S region, and the association of N-glycosylation of HBV envelope protein with the development ACLF was analyzed, as well as the association of N-glycosylation of HBV envelope protein with the severity and 90-day survival rate of ACLF. Results A total of 51 CHB patients ( 85. 0%) and 79 HBV-ACLF patients ( 87. 8%) were included in analysis. Among the CHB patients, 33 ( 64. 7%) had Asn-59 N-glycosylation and 21 ( 41. 2%) had Asn-4 N-glycosylation, while among the HBV-ACLF patients, 16 ( 20. 3%) had Asn-59 N-glycosylation and 14 ( 17. 7%) had Asn-4 N-glycosylation; there were significant differences in the numbers of cases of Asn-59 and Asn-4 N-glycosylation between the two groups ( P < 0. 001, and P = 0. 003) . There were no significant differences in liver function, HBV DNA, Model for End-Stage Liver Disease score, and 90-day survival rate between the ACLF patients with Asn-59 and Asn-4 N-glycosylation and those without such glycosylation ( P > 0. 05) . Conclusion The reduction in Asn-59 and Asn-4 N-glycosylation induced by HBV envelope protein variation may be associated with the development of ACLF.
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Key words:
- hepatitis B virus /
- liver failure /
- viral envelope proteins /
- glycosylation
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[1] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association;Severe Liver Diseases and Artificialliver Group, Chinese Society of Hepatology, Chinese Medical Association.Diagnostic and treatment guidelines for liver failure (2012 version) [J].Chin J Hepatol, 2013, 21 (3) :177-183. (in Chinese) 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) [J].中华肝脏病杂志, 2013, 21 (3) :177-183. [2]Chinese Society of Hepatology, Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B (2010 version) [J].J Clin Hepatol, 2011, 27 (1) :Ⅰ-ⅩⅥ. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2010版) [J].临床肝胆病杂志, 2011, 27 (1) :Ⅰ-ⅩⅥ. [3]WISSKIRCHEN K, METZGER K, SCHREIBER S, et al.Isolation and functional characterization of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use[J].PLo S One, 2017, 12 (8) :e0182936. [4]LIU M, ZHANG XQ, MAO Q.Features of acute-on-chronic pre-liver failure and establishment of a predictive model for risk of acute-on-chronic liver failure[J].J Clin Hepatol, 2012, 28 (10) :732-734. (in Chinese) 刘明, 张绪清, 毛青.慢加急性肝衰竭前期的概念及预警模型[J].临床肝胆病杂志, 2012, 28 (10) :732-734. [5]SARIN SK, KUMAR A, ALMEIDA JA, et al.Acute-on-chronic liver failure:Consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) [J].Hepatol Int, 2009, 3 (1) :269-282. [6]CHEN J, ZHANG J, HE QS.Role of Toll-like receptors in development and progression of nonalcoholic fatty liver disease[J].J Clin Hepatol, 2015, 31 (7) :1153-1155. (in Chinese) 陈杰, 张晶, 何秋水.Toll样受体在非酒精性脂肪性肝病发生发展中的作用[J].临床肝胆病杂志, 2015, 31 (7) :1153-1155. [7]HSU HY, CHANG MH, NI YH, et al.Long-term follow-up of children with postnatal immunoprophylaxis failure who were infected with hepatitis B virus surface antigen gene mutant[J].J Infect Dis, 2013, 207 (7) :1047-1057. [8]KOBAYASHI Y, SUZUKI Y.Evidence for N-glycan shielding of antigenic sites during evolution of human influenza A virus hemagglutinin[J].J Virol, 2012, 86 (7) :3446-3451. [9]CRISPIN M, BOWDEN TA.Antibodies expose multiple weaknesses in the glycan shield of HIV[J].Nat Struct Mol Biol, 2013, 20 (7) :771-772. [10]APPELMAN MD, CHAKRABORTY A, PROTZER U, et al.NGlycosylation of the Na+-taurocholate cotransporting polypeptide (NTCP) determines its trafficking and stability and is required for hepatitis B virus infection[J].PLo S One, 2017, 12 (1) :e0170419. [11]PRANGE R, WERR M, BIRKNER M, et al.Properties of modified hepatitis B virus surface antigen particles carrying pre S epitopes[J].J Gen Virol, 1995, 76 (Pt 9) :2131-2140. [12]YU DM, LI XH, MOM V, et al.N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contributemostly to immune escape[J].J Hepatol, 2014, 60 (3) :515-522. [13]YAO MQ, CHEN J, ZHANG J.Association between hepatitis B virus pre-S/S gene variants and HBV-related liver diseases[J].J Clin Hepatol, 2016, 32 (7) :1406-1408. (in Chinese) 姚明琦, 陈杰, 张晶.HBV前S/S区变异与HBV相关肝病的关系[J].临床肝胆病杂志, 2016, 32 (7) :1406-1408. [14]HAN Z, LV M, SHI Y, et al.Mutation of glycosylation sites in BST-2 leads to its accumulation at intracellular CD63-positive vesicles without affecting its antiviral activity against multivesicular body-targeted HIV-1 and hepatitis B Virus[J].Viruses, 2016, 8 (3) :62. [15]CHEN YL, MO YQ, ZHENG DH, et al.Patients with coexistence of circulating hepatitis B surface antigen and its antibody may have a strong predisposition to virus reactivation during immunosuppressive therapy:A hypothesis[J].Med Sci Monit, 2017, 23:5980-5985. [16]QIAO Y, LU S, XU Z, et al.Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBs Ag/anti-HBs[J].Oncotarget, 2017, 8 (37) :61719-61730.
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