HBV前C区基因变异与中医证候的相关性研究

研究慢性乙型肝炎患者HBV前C区基因变异的变化规律与中医证候的相关机制。基因芯片检测慢性乙型肝炎不同证候的HBV前C区基因变异。不同位点变异率(%)与证候相关,肝肾阴虚1764(38%),1896(68%),1899(38%);瘀血阻络1762(93%),1764(90%),1899(50%)。不同证候变异株信号强度差异显著,1762、1764;瘀血阻络>肝肾阴虚>肝郁脾虚;1862:肝肾阴虚>肝郁脾虚;>1896:肝肾阴虚>瘀血阻络>湿热中阻>肝郁脾虚;1899:瘀血阻络>肝肾阴虚>湿热中阻>肝郁脾虚。慢性乙型肝炎HBV前C区基因变异与中医证候相关,为分子证候辨证提供了一定实验依据和研究基础。     

慢性乙型肝炎患者HBV前C区G1896A、核心启动子1762/1764变异与乙型肝炎自然史、血清HBsAg定量及疾病程度的相关性

目的研究HBV前C区G1896A、核心启动子1762/1764变异与HBV自然史、血清HBsAg水平间的相关性及对疾病严重程度的影响。方法分别各选取40例HBV野生株、前C区G1896A或核心启动子1762/1764变异以及两者联合变异的慢性乙型肝炎感染者为研究对象。采用PCR反向点杂交技术检测HBV前C区G1896A位点、核心启动子1762/1764变异及HBV基因分型。同时检测HBsAg定量、HBeAg、HBV DNA定量、肝脏生化指标等。结果(1)HBV前C区G1896A、核心启动子1762/1764变异患者的年龄、ALT高于野生株感染者(P0.001),Alb低于野生株感染者(P0.001)。(2)HBV自然史免疫耐受期以野生株感染为主(P0.001),免疫清除期、低(非)复制期野生株及PC G1896A或/和BCP1762/1764变异株差异无统计学意义(P0.05),再活动期以PC G1896A或/和BCP1762/1764变异株为主(P0.001)。(3)PC G1896A或/和BCP1762/1764变异株的HBsAg水平(lgIu/mL)、HBeAg阳性率较野生株组降低(P0.001),基因C型、HBV DNA水平(≥6 lg拷贝/mL)较野生株组差异无统计学意义(P0.05)。(4)HBV PC G1896A或/和BCP1762/1764变异中肝硬化患者多于野生株(P0.05)。结论慢性HBV感染者前C区G1896A、核心启动子1762/1764变异与乙型肝炎自然史、HBsAg水平、HBeAg的状态及疾病严重程度相关。     

黎族HBV感染者其病毒基因型及C基因启动子/前C区基因突变与肝硬化和肝癌的关系

HBV感染是一个严重的公共卫生问题.在中国,慢性乙型肝炎是导致肝硬化和原发性肝癌的主要危险因素之一[1].目前,根据HBV核苷酸变异＞8％,将HBV分为A～H8种基因型[2].有研究结果显示,HBV基因型、HBV基因组前C区(PreC)第1896位核苷酸G→A(G1896A)以及其启动子(BCP) 1762位核苷酸A→T和1764位核苷酸G→A的突变(BCP A1762T/G1764A)与病毒的复制、转录、抗原表达水平以及疾病的临床过程密切相关[3-4].黎族是海南岛的原住居民,目前关于海南岛黎族肝硬化及肝癌患者HBV基因型、PreC G1896A基因突变和BCP A1762T/G1764A基因突变流行病学分布的研究鲜见报道.本研究旨在了解HBV基因型、PreC G1896A基因突变和BCP A1762T/G1764A基因突变与海南岛黎族肝硬化及肝癌患者发病机制的关系.     

慢性乙型肝炎患者HBV C基因启动子变异的临床意义

目的:探讨慢性乙型肝炎中C基因启动子(BCP)变异的临床意义。方法:采用错配PCR与限制性长度片段多态性分析(RFLP)相结合,检测35例慢性乙型肝炎患者BCP区核苷酸(nt)1762碱基A→T和1764G→A联合突变及前C区nt1896G→A终止变异。结果:在35例慢性乙型肝炎中检出BCP区T1762A1764变异8例(23％),其中6例血清HBeAg( ),2例抗HBe( ),而7例前C区A1896变异中HBeAg( )2例,抗HBe( )5例,未见T1762A1764变异和A1896变异同时出现者。结论:提示HBV毒株BCP区T1762A1764变异可能与前C区A1896变异不同,它的出现不足以导致HBeAg(—)型的慢性肝炎。     

慢性乙型肝炎中医证型与客观检测指标的相关性研究

目的:探讨慢性乙型肝炎(CHB)中医证型与患者肝功能、HBV血清标志物(HBV-M)、病毒前C区变异株等指标的关系。方法:将183例CHB患者按中医辨证分为5型(湿热中阻型、肝郁脾虚型、瘀血阻络型、肝肾阴虚型、脾肾阳虚型),分别进行肝功能、HBV-M、HBVDNA及HBV前C区变异株的检测,同时行B超测患者脾脏大小,分析证型与各项指标的相关性。结果:①湿热中阻和肝郁脾虚型患者的ALT、AST、TBA、Alb、A/G等结果明显高于其他3型,P<0.05。②TBil、DBil值异常主要见于湿热中阻型,明显高于其他4型,P<0.05。③湿热中阻和瘀血阻络型患者HBeAg阳性率、HBVDNA值明显低于其他3型,P<0.05,而前C区变异株在该两型较高,与其他3型比较,P<0.05。④脾肿大由低到高依次为湿热中阻、肝郁脾虚、脾肾阴虚、肝肾阳虚、瘀血阻络型,瘀血阻络型最高与其他4型比较,P<0.05。结论:①湿热中阻和肝郁脾虚型患者肝脏炎症反应较重,湿热中阻型是黄疸的主要证型,多出现在疾病的早期,预后较好;②瘀血阻络、肝肾阴虚、脾肾阳虚型患者肝功能相对低下,以瘀血阻络型尤为明显,多出现在疾病的后期,预后欠佳;③HBVDNA、HBeAg阳性率在实证中偏低,在虚证中偏高,与此相反HBV前C区变异率在实证中偏高,虚证中较低,提示实证者免疫功能较强,虚证者免疫功能较弱,而脾肿大的检测结果提示了CHB病势演变及预后的特点。     

乙型肝炎病毒C基因启动子双变异患者中医证型特点研究

目的：探讨HBVC基因启动子（BCP）双变异慢性乙型肝炎患者的中医证型特点。方法：选择HBsAg阳性慢性乙型肝炎患者168例进行观察。中医证型分为湿热中阻、肝郁脾虚、肝肾阴虚、瘀血阻络、脾肾阳虚5型；BCP双变异检测，采用微板核酸杂交法。结果：BCP双变异的总检出率为36．31％（61／168），其中，湿热中阻型BCP双变异检出率最高（54．24％），与其他各型比较差异均有显著性意义（P〈0．052）；肝郁脾虚型BCP双变异检出率（36．36％）虽低于湿热中阻型（P〈0．025），但却明显高于肝肾阴虚型（13．04％）及瘀血阻络型（10．53％），且差异有显著性意义（P〈0．05）；肝肾阴虚与瘀血阻络两型BCP双变异检出率均较低，两者比较差异有显著性意义（P〉0．05）。结论：HBV BCP双变异的慢性乙型肝炎患者中医证型特点以湿热中阻为主，肝郁脾虚居次，临床治疗要重视清热利湿，舒肝健脾治法或方药的选用。     

HBV BCP区1762/1764位点变异对肝脏疾病进展及预后的影响

目的:探讨乙型肝炎病毒BCP区A1762T/G1764A变异与肝脏疾病进展的关系。方法:收集78例慢性乙型肝炎患者(CHB)和125例慢性重型乙型肝炎患者(CSHB)的血清及临床资料,并对所有入组患者进行随访,采用聚合酶链反应扩增HBV BCP区基因片段,产物纯化后直接测序,检测BCP区T1762/A1764位点变异。结果:CSHB组患者A1762T、G1764A及A1762T+G1764A的变异频率分别为64.0%(80/125)、60.0%(75/125)、60.0%(75/125),CHB患者3种变异的变异频率分别为30.8%(24/78)、28.2%(22/78)、25.6%(20/78),CSHB组3种变异的变异频率均明显高于CHB组,差异有统计学意义(P0.001)。125例CSHB患者随访48周,死亡组A1762T/G1764A位点变异频率明显高于存活组,差异有统计学意义(x~2=12.42,P0.001);A1762T/G1764A位点变异组的患者累积存活率明显低于未变异组(x~2=9.742,P0.01)。结论:HBV BCP区1762/1764位点变异可能会加重HBV感染后肝脏疾病病情,并且对慢性重型乙型肝炎的发病及预后可能起重要的作用。     

慢性乙型肝炎病毒前C区基因突变与中医证型的关系

目的 :探讨乙型肝炎病毒 ( HBV)前 C区基因突变与慢性乙型肝炎中医证型的关系。方法 :将 162例慢性乙型肝炎患者按中医辨证分为 5种证型 ,应用聚合酶链反应 -单链构象多态分析 ( PCR- SSCP)银染技术检测 HBV前 C区基因变异。结果 :慢性乙型肝炎湿热中阻型患者 HBV前 C区突变率为 61.1% ( 3 3 / 5 4 ) ;瘀血阻络型为5 7.6% ( 19/ 3 3 ) ;肝郁脾虚型为 2 9.8% ( 14 / 4 7) ;肝肾阴虚型为 3 8.1% ( 8/ 2 1) ;脾肾阳虚型为 14 .3 % ( 1/ 7)。结论 :HBV前 C区突变与慢性乙型肝炎中医证型密切相关。湿热中阻型和瘀血阻络型突变率明显高于肝郁脾虚型和脾肾阳虚型。     

乙型肝炎病毒前C区和核心启动子区突变与慢性乙型肝炎病情的关系

乙型肝炎病毒（HBV）感染能导致急、慢性肝病，其中全球慢性乙型肝炎感染者近4亿。每年由于HBV慢性感染引起的肝硬化，肝细胞癌死亡患者超过47万人。而由于HBV病毒复制过程缺乏校对机制，在慢性感染的过程中发生基因突变的概率很高，相关研究最多的HBV突变株主要有：发生在翻译水平的前C区突变（G1896A）；发生在核心启动子（BCP）区，即A1762T和G1764A的联合突变；发生在HBV DNA聚合酶区的变异包括P区528、552位点的突变。研究表明，HBV前C区1896位突变以及BCP区突变普遍存在于CHB患者中，     

乙型肝炎病毒X区基因变异与原发性肝癌的关系研究

目的初步研究乙型肝炎病毒(HBV)X区基因变异与原发性肝癌的关系。方法收集39例HBV感染患者的肝(癌)石蜡组织标本,其中慢性乙型肝炎(CHB)14例、肝细胞癌(HCC)25例。采用聚合酶链式反应(PCR)方法扩增组织中HBV X区基因,并对PCR产物进行DNA测序,分析常见变异位点的变异情况。结果 1.HCC组与CHB组相比,在X区发生插入/缺失变异,联合变异的位点及例数增多,并且A1762T与G1764A常发生双突变。2.HBV X区变异频率较高位点依次是C1655T/G、A1605C/G、A1762T、G1764A、A1772B、A1645C、C1687A、G1776T。结论 HBV X区存在点突变、插入/缺失变异及联合变异,可能在HCC的发生和发展过程中起重要作用。     

应用蛋白芯片技术研究乙肝病毒所致慢性肝病中医证型与细胞因子的相关性

目的：应用蛋白芯片技术探究HBV导致的慢性肝病患者血清IL-2、IFN-γ、IL-4、TNF—α、sICAM-1、TGF-β1、TIMP-1等细胞因子与中医证型的相关性。方法：构建细胞因子蛋白芯片，对健康人群、不同中医证型的慢性乙型肝炎和乙型肝炎肝硬化患者血清中7种细胞因子进行检测。结果：①慢性乙型肝炎患者各证型IL-2水平较正常组不同程度降低；湿热中阻型患者IL4浓度为（86．43±19．24）pg／ml，与正常组比较差异无显著性意义，其余证型患者IL-4水平均显著升高；各证型组患者的TNF-α、TGF-β1、sICAM-1、TIMP-1均较正常组显著升高（P〈0．01），以湿热中阻型患者的TNF—α上升幅度最大，TGF-β1、sICAM-1及TIMP-1则以瘀血阻络型患者的升高最明显；肝郁脾虚及湿热中阻型患者血清IFN-1与正常组比较，差异无显著性意义，而另外3种证型患者血清IFN-1水平均显著低于正常组。②肝硬化除湿热内蕴型患者血清IFN-1与正常组比较差异无显著性意义外，其余各证型患者血清7种细胞因子与正常组比较，差异均有显著性意义；脾虚湿盛、脾肾阳虚、血瘀证3型患者的IL-2水平显著低于肝气郁结型，而IL4、TNF—α水平较肝气郁结型不同程度升高；TGF-β1、sICAM-1在湿热内蕴型水平最低；肝气郁结型患者的TIMP-1浓度为（167．88±14．21）ng／ml，与其他证型比较，差异均有显著性意义；湿热内蕴型患者IFN-1浓度与肝气郁结型比较，差异无显著性意义，而其余证型均低于肝气郁结型。结论：慢性乙型肝炎、乙型肝炎肝硬化患者不同中医证型与血清细胞因子有一定相关性，将细胞因子纳入HBV所致慢性肝病患者中医辨证论治体系，有利于提高中医辨证的精确性和规范性。     

慢性乙型肝炎中医证型与拉米夫定抗病毒疗效及耐药发生率的关系研究

目的：观察慢性乙型肝炎中医证型与拉米夫定抗病毒疗效及耐药发生情况的关系。方法：选择符合抗病毒治疗的慢性乙型肝炎患者150例,按中医辨证分湿热中阻型、肝郁脾虚型、肝肾阴虚型、脾肾阳虚型、瘀血阻络型。各型患者分别服用拉米夫定抗病毒治疗3年,观察拉米夫定对不同中医证型患者的HBV DNA的转阴率以及耐药发生情况与中医证型之间的关系。结果：湿热中阻型患者HBV DNA的转阴率最高,而耐药发生率最低,与其他证型比较差异有统计学意义。结论：慢性乙型肝炎患者拉米夫定抗病毒的疗效及耐药发生率与中医证型相关。     

不同中医证型慢性乙型肝炎轻度患者肝组织病理研究

目的：研究不同中医证型的慢性乙型肝炎（CHB）轻度患者肝组织病理特点,并探讨其临床意义。方法：将310例CHB轻度患者进行中医辨证分型,采用Menshini法1秒钟经皮肝穿取肝组织进行炎症和纤维化程度判断,并与车祸死亡正常人作对照,同时荧光定量PCR法检测患者血清HBVDNA水平。结果：①肝组织炎症≥G2、肝纤维化≥S2等级的患者年龄明显高于肝组织炎症〈G2、肝纤维化〈S2等级的年龄;②各中医证型患者肝组织炎症级别≥G2的比率明显高于正常组,但证型间比较差异均无显著性意义;③各中医证型患者肝组织纤维化程度≥S2的比率明显高于正常组,但证型间比较仅肝肾阴虚和脾肾阳虚两型明显高于肝郁脾虚和湿热中阻型;④各中医证型间HBVDNA水平比较,肝肾阴虚和脾肾阳虚两证型明显低于肝郁脾虚型,其他证型之间差异无显著性意义。结论：CHB轻度患者至少有1／3的患者需要抗病毒治疗,而且年龄越大越有必要;在控制肝脏炎症方面,辨证治疗应多加倡导,在抗纤维化治疗方面应重视补肾法研究。     

58例肝癌患者手术前后中医复合证证候特点初步研究

目的:通过观察原发性肝癌患者手术前后中医复合证证候分布与转变情况,初步揭示肝癌患者手术前后的中医复合证证候变化特点,为手术后肝癌的辨证论治提供科学依据.方法:参照《中药新药临床研究指导原则》建立肝癌中医复合证证候定性和量化诊断标准,采用自身前后对照的方法,对58例肝癌手术患者手术前后中医复合证证候特点进行初步研究.结果:中医复合证证候分布及变化情况:肝癌患者手术前肝血瘀阻证、湿热内蕴证所占比例较高,分别为22.1％、20.9％;肝癌患者手术后以湿热内蕴证、脾气虚弱证所占比例较高,分别为21.8％、21.0％;手术后肝血瘀阻证减少,脾气虚弱证增多,两者手术前后差异有统计学意义(P＜0.05);其余各证手术前后差异无统计学意义(P＞0.05).中医复合证证候量化评分结果:肝癌患者手术前量化评分最高的两个证候是:湿热内蕴证22.66分、脾气虚弱证17.75分;手术后量化评分最高的两个证候是:脾气虚弱证24.98分、湿热内蕴证23.31分:手术后肝血瘀阻证减少,脾气虚弱证增多,两者手术前后差异有统计学意义(P＜0.05);其余各证手术前后差异无统计学意义(P＞0.05).结论:肝癌患者手术前后均呈现肝血瘀阻证和脾气虚弱证的症状,因此需重视活血化瘀、健脾益气,但术后肝血瘀阻证有所减少,脾气虚弱证增多,应该对活血化瘀和健脾益气力度有所调整,肝癌术后中医辨证论治应更重视健脾益气.肝癌患者手术前后湿热内蕴证均较多,手术前后变化无差异,故肝癌患者手术前后均应重视清热利湿.     

慢性病毒性肝炎279例病理诊断与中医证型的关系

目的:探讨慢性病毒性肝炎病理组织学诊断与中医辨证分型之间的关系,为中医辨证提供客观依据。方法:279例均为住院患者,男227例,女52例。全部病例经肝活检证实,其中轻度142例,中度91例,重度46例。慢性乙型肝炎274例,慢性丙型肝炎5例。中医辨证:湿热中阻53例,肝郁脾虚64例,肝肾阴虚29例,脾肾阳虚7例,血瘀血热101例,气阴两虚25例。临床治疗以辨证施治为主。结果:(1)279例慢性肝炎在病理诊断分型中,轻度占50.9%、中度占32.6％、重度占16.4％。(2)在轻度慢性肝炎中,湿热中阻、肝郁脾虚及肝肾阴虚证明显高于血瘀血热证.P=0.01、P<0.05。(3)湿热中阻、肝郁脾虚证的病理诊断分布情况依次为轻度>中度>重度,P<0.01、P<0.05;血瘀血热证轻度与中度分别>重度,P<0.05。但该证在重度中的发生率高于其他证型。(4)脾肾阳虚与气阴两虚证在各病理分型中的分布均无显著差异,P>0.05。结论:(1)慢性肝炎患者以轻度居多,占半数以上。(2)慢性肝病的病变早期以湿热中阻、肝郁脾虚为主证特点,病变部位多在气分;随着肝脏病理损害加重,病变部位及主导证型渐由气分至血分,以血瘀血热为主证特点。(3)治疗上主张早期宜注重清解湿热,疏肝健脾;中、晚期宜重视活血化瘀,凉血解毒。     

肝硬化中医证型与Child—Pugh分类相关性的研究

目的:从中医角度探讨肝硬化证型与Child-Pugh分类之间的关系,以便正确评估不同证型肝硬化患者肝贮备功能,建立肝硬化辨证分型的客观指标。方法:将110例确诊为肝硬化病人按中医辨证分6个证型组,同步检测Child-Pugh分类要求检测的项目。结果:肝硬化中医证型不同,Child分类不同。肝郁脾虚型以Child A级为多(占80％);气滞血瘀型以Child B级为多(占46.67％);脾肾阳虚和肝肾阴虚型以Child C级为多(分别占56.25％和54.54％)。研究还发现随着中医病理发展,中医证型也由肝郁脾虚迢渐向湿热蕴结以至脾肾阳虚和肝肾阴虚发展,而Child分级也由A级向C级变化。结论:可将Child分级评分作为肝硬化辨证分型诊断的客观依据之一。     

慢性乙型肝炎病毒基因分型与中医辨证规律初探

目的研究慢性HBV基因型与慢性乙型肝炎（chronichepatitisB,CHB）中医辨证的相关性。方法在中医辨证基础上,测定300例CHB患者的外周血HBV基因型。结果①HBV基因型分布特点：B型和C型占大多数,分别为48例（16．0％）和233例（77．7％）。②中医证型分布特点：肝郁脾虚型和瘀血阻络型比例较大,分别为149例（49．7％）和110例（36．7％）,HBV基因型在各中医证型间的分布差异无统计学意义。③瘀血阻络型患者中21．8％（24／110）诊断为重度,高于肝郁脾虚型的12．1％（18／149）。结论中国人感染HBV,基因c型明显高于其他型;瘀血阻络型肝损害较重;HBV基因型与中医证型无明显相关性,临床治疗CHB应以辨证论治为主,不必拘泥于基因分型。     

Hepatitis B virus genotype and basal core promoter/precore mutations are associated with hepatitis B‐related acute‐on‐chronic liver failure without pre‐existing liver cirrhosis

Summary. The study was undertaken to investigate the features and clinical implications of hepatitis B virus (HBV) genotypes, basal core promoter (BCP) and precore (PC) mutations in hepatitis B‐related acute‐on‐chronic liver failure (HB‐ACLF). Samples from 75 patients with HB‐ACLF and without pre‐existing liver cirrhosis and 328 age‐matched patients with chronic hepatitis B (CHB) were analyzed. HBV genotype and BCP/PC mutations were determined by direct sequencing. Mutations at 8 sites of the BCP/PC region were compared between the two groups of patients. A significantly higher ratio of genotype B to C was found in patients with HB‐ACLF than in patients with CHB (30.7–69.3%vs16.5–82.6%, P < 0.01). Single mutations including T1753V (C/A/G), A1762T, G1764A, G1896A and G1899A and triple mutations T1753V/A1762T/G1764A and A1762T/G1764A/C1766T (or T1768A) were more frequently detected in patients with HB‐ACLF than in patients with CHB. Correspondingly, BCP/PC wild‐type sequences were absent in patients with HB‐ACLF in contrast to 27.1% in patients with CHB. The BCP/PC mutations were found to be associated with increased HBeAg negativity, higher alanine aminotransferase level and lower viral load. Patients with HB‐ACLF infected with the PC mutant virus had a higher mortality. The findings suggest that patients with CHB infected with genotype B with BCP/PC mutations were more likely to develop HB‐ACLF than those with genotype C with wild‐type BCP/PC regions, and patients with HB‐ACLF with the PC mutation had increased risk of a fatal outcome.     

Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients

The aim of the study was to investigate the prevalence of mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and their association with hepatocellular carcinoma. A total of 341 untreated older HBV patients were divided into three groups: chronic hepatitis B (CHB, 185), cirrhotic hepatocellular carcinoma (LC-HCC, 113) and non-cirrhotic hepatocellular carcinoma (non-LC-HCC, 43). HBV BCP and PreC mutations and genotypes were determined by direct sequencing. Using univariate analysis, age (≥ 45 years), single mutations including A1896 and A1899 and multiple mutations T1762/A1764 + A1896, T1762/A1764 + A1899 and T1762/A1764 + A1896 + A1899 were more frequently detected in LC-HCC and non-LC-HCC patients than in CHB patients. BCP T1762/A1764 mutations were highly detected in LC-HCC patients than in CHB patients. Multivariate logistic regression analysis (adjusted for age and gender) revealed that among HBeAg-positive patients, BCP T1762/A1764 mutations (OR, 5.975; P = 0.05), PreC A1899 mutation (OR, 4.180; P = 0.013) and multiple mutations T1762/A1764 + A1899 (OR, 6.408; P = 0.006) were independently associated with the development of LC-HCC; PreC A1899 mutation (OR, 7.347; P = 0.034) was also independently associated with the development of non-LC-HCC. On the other hand, among HBeAg-negative patients, PreC A1896 mutation (OR, 5.176; P = 0.002) and multiple mutations T1762/A1764 + A1896 (OR, 4.149; P = 0.007) were independently associated with the development of non-LC-HCC. These results indicated that older age (≥ 45 years) was associated with LC-HCC and non-LC-HCC development. BCP T1762/A1764 mutations and PreC A1899 mutation were associated with the LC-HCC development in HBeAg-positive patients. PreC A1896 mutation was associated with the non-LC-HCC development in HBeAg-negative patients.     

Hepatitis B virus genotype B and mutations in basal core promoter and pre-core/core genes associated with acute-on-chronic liver failure: a multicenter cross-sectional study in China

Background and aim

In China, acute-on-chronic liver failure (ACLF) is mostly caused by hepatitis B virus (HBV). However, the mechanism remains unclear. This study aims to investigate the association between both HBV genotype and mutations in basal core promoter (BCP) and pre-core/core (pre-C/C) regions with the development of HB-ACLF.

Methods

A multicenter cross-sectional study was performed in China. Serum samples from 522 patients were analyzed, including 231 patients with mild-chronic hepatitis B (CHB-M), 84 with severe-chronic hepatitis B (CHB-S) and 207 with HB-ACLF. HBV genotype and related mutations in the BCP and pre-C/C regions were determined by direct sequencing.

Results

A significantly higher ratio of HBV genotype B to C was detected in HB-ACLF patients than in CHB-M or CHB-S patients. The A1762T/G1764A, A1846T and G1896A mutations were significantly more common in HB-ACLF patients infected with either genotype B or C as compared with CHB-M, whereas the C1913A/G and A2159G mutations were more associated with HB-ACLF in genotype C patients. Comparing with CHB-S, the A1762T/G1764A mutation in genotype B and the A2159G mutation in genotype C were significantly more common in HB-ACLF patients. A multivariate analysis showed that factors such as HBV genotype B, age ≥40 years and A1762T/G1764A, A1846T and G1896A mutations were independently associated with the development of HB-ACLF.

Conclusion

Chronic HBV infection with genotype B, A1762T/G1764A, A1846T and G1896A mutations has a higher possibility to develop HB-ACLF. These virological factors could serve as possible molecular markers for prediction of the clinical outcomes of chronic HBV infection.