目的比较人免疫缺陷病毒(human immunodeficiency virus,HIV)/乙型肝炎病毒(hepatitis B virus,HBV)合并感染者与HBV单一感染者外周血HBV核心(core,C)蛋白和多聚合酶(polymerase,P)蛋白的特异性细胞毒性T细胞(cytotoxic T lymphocyte,C...目的比较人免疫缺陷病毒(human immunodeficiency virus,HIV)/乙型肝炎病毒(hepatitis B virus,HBV)合并感染者与HBV单一感染者外周血HBV核心(core,C)蛋白和多聚合酶(polymerase,P)蛋白的特异性细胞毒性T细胞(cytotoxic T lymphocyte,CTL)表位变异的差异,探讨HIV/HBV合并感染者肝病进程加快的可能致病机制。方法收集慢性HBV感染者的基本检查结果和血标本,并依据抗病毒前HIV抗体检测结果,分为HIV/HBV合并感染组和HBV单一感染组。提取HBV DNA,巢式PCR法扩增HBV C基因与P基因并送PCR产物测序,ContigExpress软件进行序列拼接,Vector NTI软件进行序列比对,参照相应基因型标准序列,分析2组患者的HBV CTL表位变异差异。结果成功扩增的HBV C基因与P基因的患者共151例,其中HIV/HBV合并感染者83例,HBV单一感染者68例。HIV/HBV合并感染组较HBV单一感染组CTL表位变异发生率均偏高,其中C18-27、C88-96、C139-148表位变异发生率差异比较有统计学意义(χ^2=7.509,P=0.006;χ^2=3.902,P=0.048;χ^2=4.238,P=0.040)。HIV/HBV合并感染组的C18-27表位主要变异氨基酸的类型增多,出现新的S26N(4.8%)、S26T(4.8%)变异类型,而C88-96、C139-148表位主要变异氨基酸相同(L95I、T147A)。结论HIV/HBV合并感染可增加HBV C蛋白和P蛋白的CTL表位变异,尤其是C18-27、C88-96、C139-148表位变异。C蛋白CTL表位变异增多可能与HIV/HBV合并感染肝病进程加快的致病机制相关。展开更多
HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients expe...HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients experiencing higher liver-related morbidity,hospitalization rates,and mortality than those with HBV monoinfection.Surprisingly,an increasing number of studies have shown that hepatitis B surface antigen(HBsAg)clearance rates in HIV/HBV coinfection can reach over 10%,which is significantly higher than in HBV monoinfection.In this review,we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection,including baseline HBsAg levels,baseline HBV DNA levels,baseline CD4+T cell-counts,and immune reconstitution inflammatory syndrome-related hepatic flare.Based on current evidence,we further discuss a potential mechanism for HBsAg clearance:HIV-induced immunodeficiency,particularly the depletion of CD4+T cells,may unexpectedly disrupt preexisting HBV-specific tolerance.After antiretroviral therapy(ART)in HIV/HBV coinfected individuals,partial immune system reconstitution occurs,and the reconstituted immune system,no longer tolerized by HBV,effectively clears HBV-infected hepatocytes,triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance.Additionally,emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve:PD-1/PD-L1 pathway inhibition,cytokine induction promoting immune cell recruitment and an inflammatory environment,and natural killer(NK)cell functional remodeling.These collective observations highlight the important role of immune modulation in HBV clearance,providing insights that can facilitate the development of a functional HBV cure.Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2304800)the Guangzhou Science and Technology Plan Project(2025 Basic and Applied Basic Research Project,No.2025A04J4146).
文摘HIV(human immunodeficiency virus)/HBV(hepatitis B virus)coinfection remains a significant public health challenge.HIV infection affects the natural course of chronic HBV infection,with HIV/HBV coinfected patients experiencing higher liver-related morbidity,hospitalization rates,and mortality than those with HBV monoinfection.Surprisingly,an increasing number of studies have shown that hepatitis B surface antigen(HBsAg)clearance rates in HIV/HBV coinfection can reach over 10%,which is significantly higher than in HBV monoinfection.In this review,we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection,including baseline HBsAg levels,baseline HBV DNA levels,baseline CD4+T cell-counts,and immune reconstitution inflammatory syndrome-related hepatic flare.Based on current evidence,we further discuss a potential mechanism for HBsAg clearance:HIV-induced immunodeficiency,particularly the depletion of CD4+T cells,may unexpectedly disrupt preexisting HBV-specific tolerance.After antiretroviral therapy(ART)in HIV/HBV coinfected individuals,partial immune system reconstitution occurs,and the reconstituted immune system,no longer tolerized by HBV,effectively clears HBV-infected hepatocytes,triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance.Additionally,emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve:PD-1/PD-L1 pathway inhibition,cytokine induction promoting immune cell recruitment and an inflammatory environment,and natural killer(NK)cell functional remodeling.These collective observations highlight the important role of immune modulation in HBV clearance,providing insights that can facilitate the development of a functional HBV cure.Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.
