慢性乙型肝炎患者HBV前C区及BCP区变异与血清细胞因子的关系

目的探讨乙型肝炎e抗原(HBeAg)阴性和阳性慢性乙型肝炎(CHB)患者乙型肝炎病毒(HBV)前C区、基本核心启动子(BCP)区变异特点以及与血清细胞因子干扰素(IFN)-γ、白细胞介素(IL)-10水平的关系。方法将120例HBV DNA阳性CHB患者(HBeAg阴性和阳性各60例)与60例健康体检者(对照组)纳入研究。荧光定量聚合酶链反应(PCR)法检测HBeAg阴性和阳性组患者HBV DNA水平,直接测序法检测两组前C区G1896A变异及BCP区A1762T和G1764A变异,双抗夹心酶联免疫吸附试验检测血清细胞因子IFN-γ/、IL-10的水平。结果 120例HBV DNA阳性CHB患者HBV前C区和BCP区变异总检出率为60.00%(72/120),其中HBeAg阴性组变异检出率为80.00%(48/60),HBeAg阳性组变异检出率为40.00%(24/60),两组比较,差异有显著性(x~2=20.00,P=0.000)。HBeAg阴性组G1896A变异(38.33%)和联合变异(G1896A、A1762T和G1764A同时变异,25.00%)的检出率明显高于HBeAg阳性组(16.67%、0.00%)(分别x~2=7.06,P=0.008;x~2=17.14,P=0.000)。变异组血清IFN-7水平为(102.33±27.20)pg/mL,明显高于无变异组(79.18±16.43)pg/mL及对照组(35.77±4.23)pg/mL(分别t=5.72,t=19.33,均P=0.000);变异组血清IL-10水平为(28.13±7.00)pg/mL,明显高于无变异组(13.91±5.42)pg/mL及对照组(13.68±2.27)pg/mL(分别t=12.50,t=15.65,均P=0.000)。结论 G1896A变异和联合变异更常见于HBeAg阴性CHB;G1896A和A1762T/G1764A变异与血清细胞因子IFN-γ和IL-10水平升高有关。     

乙型肝炎病毒核心基因启动子变异与患者血清病毒载量和标志物及肝功能的关系

目的探讨乙型肝炎病毒核心基因启动子(HBV BCP)变异与患者血清病毒载量(HBV DNA)和标志物及肝功能的关系。方法采用PCR微板核酸杂交结合ELISA检测显示技术,对176例HBV慢性感染者血清进行检测BCP区核苷酸(nt)1762A→T和1764G→A联合突变。结果BCP变异在HBeAg阴性病例的阳性率为49.4%,显著高于HBeAg阳性病例的阳性率33.3%(P<0.05);BCP变异阳性组的HBV DNA含量显著高于阴性组的含量(P<0.01);BCP变异阳性组HBV DNA含量在HBeAg阳性病例及HBeAg阴性病例中均较BCP变异阴性组高(P<0.01);BCP变异阳性组对肝功能的损害明显高于阴性组(P<0.01)。结论BCP变异可引起HBeAg阴转,病毒复制水平提高;HBV血清标志物联合HBV DNA同步检测,具有重要的临床应用价值;对HBsAg阳性、HBeAg阴性患者需要进一步检测HBV DNA,以免由于基因变异导致将HBeAg阴性者误认为病毒的免疫清除或静息而延误抗病毒治疗时机;BCP变异可使病情加重。     

HBV genotypes prevalence, precore and basal core mutants in Morocco

The study of hepatitis B virus (HBV) genomic heterogeneity has become a major issue in investigations aimed at understanding the relationship between HBV mutants and the wide spectrum of clinical and pathological conditions associated with HBV infection. The objective of the current study was to find out the pattern of HBV genotypes circulating in Morocco and to investigate the precore (PC) and basal core promoter (BCP) mutants' status in Moroccan chronic hepatitis B patients. Viral genotypes were determined in 221 chronic carriers using INNO-LiPA HBV assay and hemi-nested PCR. Phylogenetic analysis was performed in 70 samples, and multiplex PCR method was used to confirm some genotyping results. PC and CP mutants were determined using Inno-Lipa. All isolates were successfully genotyped. The genotype distribution was D in 90.45% of cases, A (5.9%), E (1 case), and mixed genotypes (5 A/D and 2 D/F) in 3.17% patients. HBV carried in the HBV/D samples could be assigned to D7 (63.3%), D1 (32.7%) and 2% of strains to each D4 and D5, all HBV/A belonged to A2 subgenotype and HBV/E strain could not be sub-genotyped. In 70 studied strains, HBV mutants were detected in 88.6% of cases; PC mutants were detected in (40%) of patients and 21.5% present a mixture of wild type and G1896A mutation. BCP mutants were observed in 65.7% of cases, 22.9% were found to have the T1762/1764A double mutation, 18.6% had A1762/1764T mutation and 22.9% of patients showed the A1762T/G1764A double mutation with either A1762T/G1764T mutation. Co-infection by PC and BCP mutants was detected in 52.9% of cases. Movement from place to place most likely shapes the observed genotype distribution and consequent prevalence of genotypes other than A2 or D7 in this population. High circulation of PC and BCP mutants is common in chronic hepatitis B infection in Morocco.     

Subgenotype D5, BCP and MHR mutations in hepatic complications among hepatitis B virus infected patients from Orissa,India

The study was undertaken to investigate the clinical implications of hepatitis B virus (HBV) genotypes, basal core promoter (BCP), precore (PC) and surface gene mutations in HBV infected patients from Orissa, southeastern India. HBV infections were identified by serology testing and HBV DNA amplification by polymerase chain reaction among the 152 patients. After sequencing, surface gene mutation were studied by sequence analysis as well as by using BLOSUM scores and BCP mutations were studied only by sequence analysis. A high proportion of HBV/D5 (66.0%) was found among the study samples having significant relation with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients (p < 0.05). The BCP mutation, TA (81.4%) and C1753/TA (75.0%) was found in significant proportion (p < 0.05) among HCC cases and in fact a gradual increase in these mutations were noted between inactive carriers (IC) to HCC group and also showed higher viral load. An increasing trend of major hydrophilic region (MHR) mutations in S gene was also observed from IC (56.0%) to chronic liver disease (CLD) (60.4%) to LC (72.4%) to HCC (95.0%) patients. In conclusion, our study suggests that the predominant HBV subgenotype HBV/D5 with high viral load and BCP mutations (double and triple) and high mutations in MHR region was significantly associated with advanced liver disease (LC and HCC) and might act as predictor of severe hepatic complications.     

132例乙型肝炎病毒感染者基本核心启动子变异分析

目的研究乙型肝炎病毒（HBV）感染者基本核心启动子（BCP）变异情况。方法收集HBV感染者血清标本132份(HBV DNA均阳性),用半巢式聚合酶链反应扩增HBV C基因部分片段,产物纯化后直接测序,检测BCP T1762/A1764变异。用S基因错配聚合酶链反应（PCR RFLP）法确定HBV基因型。结果51例乙型肝炎e抗原(HBeAg)阳性患者BCP T1762/A1764双变异检出率为27.45%,81例HBeAg阴性患者BCP T1762/A1764双变异检出率为62.96%,两组比较,差异有高度显著性（χ2=15.79,P＝0.00）。 BCP T1762/A1764双变异的HBV感染者B基因型检出率为33.85%,明显低于C基因型的检出率66.15%（χ2=24.25,P＝0.00）。结论HBV感染者普遍存在BCP T1762/A1764双变异,以C基因型感染者多见。     

贵州省乙型肝炎病毒前C区及基本核心启动子变异分布

目的调查贵州省乙型肝炎病毒(HBV)前C区A1896、基本核心启动子区(BCP) T1762/A1764变异分布。方法收集贵阳、遵义、凯里、都匀4地区不同民族无症状携带者(ASC)、慢性肝炎(CH)、肝炎肝硬化(LC)、肝细胞肝癌(HCC)患者血清482份,用测序及限制性片段长度多态性检测A1896、T1762/A1764变异,用S基因PCR-RFLP确定基因型。结果A1896、T1762/A1764变异检出率分别为23.03%和29.67%。汉族感染者A1896、T1762/A1764变异检出率为27.64%和36.04%,高于侗、苗、布依族感染者合并后的7.96%、8.85%(P<0.01)。A1896变异在B、C基因型中的分布为20.34%和27.13%(P>0.05),T1762/A1764变异为18.97%和46.28%(P<0.01)。A1896、T1762/A1764变异在HBeAg阴、阳性组间的分布差异有统计学意义(P值均<0.01)。从ASC到HCC组,A1896、T1762/A1764变异分布逐渐增高,LC、HCC组的检出率明显高于CH和ASC组(P值均<0.01)。A1896、T1762/A1764变异的分布:贵阳(分别为31.79%和41.06%)高于遵义(10.94%和14.06%)、都匀(8.64%和11.1I%)及凯里(2.86%和2.86%),但多因素logistic回归分析在控制了HBeAg、HBV基因型及临床类型影响后,在地区间分布差异无统计学意义。结论A1896、T1762/A1764变异在贵州省不同民族间分布有一定差异。C型感染者易发生T1762/A1764变异,两种变异均与疾病进展有关。     

乙型肝炎病毒C基因启动子变异检测方法的建立

目的 建立乙型肝炎病毒（HBV）C基因启动子（BCP）变异的限制性片断长度多态性（RFLP）检测方法,更好地了解BCP变异的发生与乙型病毒性肝炎（乙肝）的病情、预后以及治疗的影响。方法 结合引物设计软件Primer Premier5.0,选定保守区域,设计了2对最佳引物,建立了HBV BCP变异检测PCR-RFLP的实验方法。结果 对34例不同乙肝患者进行BCP变异检测发现：肝硬化（LC）组和慢性乙型肝炎（CHB）组中发生变异的例数明显高于无症状感染者（Asl）（χ2值分别为6.39和3.98,P〈0.05）。并且HBeAg（-）组发生变异的例数明显高于HBeAg（＋）组（χ2=4.60,P〈0.05）,结论该方法操作简便、敏感度与特异性高、结果 可靠,并可用于较大范围调查该变异株的流行情况,为临床进一步诊断和治疗提供了科学的依据,同时对人们进一步了解HBVBCP变异的发病机制具有重要意义。     

乙型肝炎肝硬化患者与乙型肝炎病毒携带者乙型肝炎病毒X基因序列比较研究

目的研究乙型肝炎肝硬化患者与乙型肝炎病毒（HBV）携带者HBV X基因序列的差异。方法对20例标本的PCR产物进行直接测序;并对3例乙型肝炎肝硬化患者和3例无症状HBV携带者HBV DNA的扩增片段进行克隆测序,并分析比较。结果肝硬化患者中X基因核心启动子双突变T1762/A1764、G1719T、T1727G/A、G1730C、T1753C等变异高于HBV携带者;前者X启动子区变异率明显高于后者;乙型肝炎肝硬化同一患者X区不同克隆之间的碱基序列同源性为91.3%-99.7%,而HBV携带者为96.0%-100.0%。结论乙型肝炎肝硬化患者,HBV DNA X区的CP启动子区以及X启动子区变异程度明显高于HBV携带者,同时乙型肝炎肝硬化患者体内存在变异程度更大的HBV准种群。     

HBsAg无症状携带者乙型肝炎病毒核心基因启动子突变的研究

目的了解HBsAg无症状携带者乙型肝炎病毒(HBV)核心基因启动子双突变(nt1762 A→T,nt1764 G→A)发生情况及其与基因型、病毒量和HBeAg的关系。方法 HBsAg无症状携带者从隆安研究队列中选择,用套式聚合酶链反应(nested PCR)对研究对象血清HBV核心基因启动子、S基因扩增、序列分析及基因分型,用HBV引物和双标记的TaqMan探针扩增和定量病毒DNA。结果观察开始时核心基因启动子为野毒株的109例观察对象,3年后双突变平均年发生率为2.8%;观察开始时已发生nt1762或nt1764点突变的59例对象,3年后另一个位点也发生突变的平均年发生率为6.8%,两率差异有统计学意义(χ2=5.109 0,P<0.05)。nt1762 A→T突变组HBeAg阳性率(45.5%,10/22)与nt1764 G→A突变组HBeAg阳性率(10.8%,4/37)差异有统计学意义(χ2=9.149,P<0.05)。20例基因型B未发生双突变,重组基因型年双突变率为4.8%(2/14),基因型C年突变率为3.1%(7/75),各基因型间突变率差异无统计学意义(P>0.05)。5例双突变发生后HBeAg仍然阳性者病毒量有下降趋势,而另5例突变发生后HBeAg阴性者其病毒量有升有降。结论 HBV核心基因启动子双突变年发生率较高,这两个位点中的任何一个发生突变是双突变的过渡形式,双突变与基因型无关,nt1764 G→A突变与HBeAg阴性有关。     

海南岛乙型肝炎病毒BCP/PreC基因突变及临床意义的研究

目的探讨乙型肝炎病毒(HBV)前C区G1896A、基本核心启动子(BCP)A1762T/G1764A与HBV复制水平和肝功能之间的关系。方法提取患者血清DNA,采用聚合酶链反应(PCR)方法扩增包含HBV C基因启动子和前C区的核苷酸链(nt1643-nt2112)对PCR产物进行DNA测序。结果在83例CHB患者中,共检出BCP A1762T/G1764A突变株25例(30.12%)。BCP突变组ALT(211.56±81.58)U/L和TBIL(55.17±28.50)μmol/L显著地高于BCP区未突变组(P﹤0.05)。前C区G1896A突变组HBV DNA的水平(4.86±1.30)显著地低于前C区未突变组(5.42±1.15)(P﹤0.05)。结论 BCP突变A1762T/G1764A双突变可能导致HBV致病力增强,更易引起严重的肝脏损害;前C区G1896A突变可能会降低HBV的复制能力。     

乙型肝炎病毒前C区/BCP区突变对血清HBV DNA含量的影响

目的利用基因芯片技术检测乙型肝炎病毒(HBV)前C区/BCP区基因突变,探讨前C区/BCP区基因突变后血清HBV DNA水平的变化。方法应用基因芯片技术检测95例慢性乙肝的HBV前C区1896、1814及HBV C基因启动子(BCP)1762、1764四位点突变,同时用荧光定量PCR检测血清HBV DNA含量。结果95份血清标本中,有91份分别检测到了HBV前C区/BCP区基因突变,阳性率95.8%,其中G1896A突变33例(36.3%),A1762T G1764A联合突变64例(70.3%),G1896A A1762T G1764A联合突变22例(24.2%),未检测到A1814C突变毒株。G1896A A1762T G1764A联合突变后,血清HBV DNA水平较未变异组降低(P<0.05),其它各组则无显著变化。结论应用基因芯片法可同时检测HBV多个突变位点。乙型肝炎病毒前C区/BCP区突变对血清HBV DNA含量有一定的影响。     

乙型肝炎病毒基因型和前C及基本核心启动子突变与乙型肝炎疫苗阻断母婴传播的关系

目的探讨乙型肝炎（乙肝）病毒（HBV）基因型和前C及基本核心启动子（BCP）突变与乙肝疫苗阻断母婴传播的关系。方法采集江苏省16对乙肝疫苗阻断失败的母婴血清样本32份,以及88对阻断成功的母婴血清样本176份。以型特异性引物PCR法检测16对乙肝疫苗阻断失败的母婴和88例阻断成功的母亲血清样本中HBV基因型,用PCR产物直接测序法检测HBV前C/ BCP突变,采用Clustal W 1．8软件进行序列分析。结果在16例阻断失败的母亲中,15例（93．8%）为HBeAg阳性,且均为C型（15/15,100%）;88例阻断成功的母亲中,51例（58．0%）为HBeAg阳性,其中C基因型占45．1%（23／51）。在HBeAg阳性母亲中,阻断失败组的C基因型检出率明显高于阻断成功组（X~2=14．3,P=0．003）。但在C基因型HBeAg阳性母亲中,阻断成功组与失败组的T1762/ A1764突变率差异无统计学意义（分别为13．3%和33．3%,P=0．4）,且均无A1896突变。结论感染HBV基因C型的母亲可能更易导致乙肝疫苗阻断失败,而前C/BCP基因突变与阻断母婴传播无关。     

广西壮族自治区肝癌高发区HBV基因型、BCP/前C区突变与肝癌相关性的研究

目的 研究广西壮族自治区(广西)扶绥县肝癌高发区HBV基因型、基本核心启动子(BCP)/前C区突变与肝癌的关系。方法 采用病例对照方法收集53例肝癌患者和70例HBV健康携带者的血清,提取HBV DNA,用巢式PCR扩增 HBV S区、BCP/前C区,扩增产物纯化后测序,分析基因型、基因突变与肝癌发生的关系。结果 BCP区A1762T/G1764A及前C区T1858C在病例组中的突变率高于对照组,分别为94.3% vs. 75.7%(P=0.006)和50.9% vs. 31.4%(P=0.029);A1775G在对照组中的突变率高于病例组28.6% vs.13.2%(P=0.041)。多因素logistic回归分析显示,HBV A1762T/G1764A和T1858C突变是肝癌发生的危险因素,OR值分别为5.459(95%CI:1.397~21.332,P=0.015)和3.881(95%CI:1.462~10.305,P=0.006);A1775G突变是肝癌发生的保护因素,OR=0.192(95%CI:0.059~0.622,P=0.006)。结论 HBV C基因型是广西肝癌高发区的主要流行株,HBV BCP区A1762T/G1764A、A1775G、前C区T1858C 突变与HBV相关肝癌的发生有密切关系。     

HIV-1/HBV共感染患者HBV病毒基因组前S区、BCP区和前C区的变异

目的探讨乙型肝炎病毒(HBV)合并人类免疫缺陷病毒1型(HIV-1)感染者和HBV单独感染者HBV基因组三个重点区域的变异。方法收集湖南省HIV-1/HBV合并感染患者(试验组)和HBV单独感染患者(对照组)血清各40份,进行HBV全基因组扩增及测序,并对突变位点进行分析。结果有59份血清HBV成功分型和测序,其中试验组21份,对照组38份,试验组与对照组HBV载量值和不同基因型比较,差异均有统计学意义(均P0. 05)。试验组4例患者血清标本HBV在前S区22个氨基酸发生变异,12例在前C区和BCP区45个核苷酸发生突变,试验组和对照组前S区氨基酸总体缺失突变率分别为0. 60%、0. 64%,差异无统计学意义(χ~2=0. 042,P 0. 05)。试验组与对照组前C区和BCP区各个主要突变位点变异发生率比较,差异无统计学意义(均P 0.05),试验组和对照组前C区和BCP区总体变异发生率分别为1. 36%、1. 73%,差异无统计学意义(χ~2=1. 920,P 0. 05)。结论共感染患者的HBV变异水平与单感染患者基本一致,短时间内HIV-1暂未对HBV的进化突变造成显著影响。     

乙型肝炎病毒前S缺失突变与肝癌关系的巢式匹配病例对照研究

目的了解乙型肝炎病毒(HBV)前S基因缺失突变是否是肝癌的危险因素以及它的作用是否受HBV核心基因启动子双突变的混淆影响。方法按巢式匹配病例对照研究的方法,从隆安研究队列中选择33对病例(肝癌患者)和对照(HBsAg无症状携带者),配对的条件之一是病例和对照HBV核心基因启动子序列相同,用套式聚合酶链反应(nested PCR)对研究对象血清HBV前S基因扩增和序列分析。结果肝癌患者组前S基因缺失突变率(45.5%,15/33)显著高于对照组(6/33,18.2%)(χ2=7.364,P0.01);男女间突变率无显著性差异(28%与43.8%,χ2=1.386,P0.05)。多因素条件logistic回归分析结果显示,前S缺失突变是肝癌的危险因素(危险比为7,95%可信区:0.861-56.894),而HBeAg,抗-HBe及肝功能则与肝癌无关。核心基因启动子双突变组与核心基因启动子野毒株组之间的前S缺失突变率无显著性差异(χ2=0.597,P0.05)。结论HBV前S缺失突变是肝癌的独立的危险因素,它的发生及作用与核心基因启动子双突变无关。     

广西地区乙型肝炎病毒无症状携带者乙型肝炎病毒前C区突变分析

目的 调查广西地区乙型肝炎病毒（HBV）无症状携带者HBV前C区基因突变株的流行情况。方法 用套式聚合酶链反应（PCR)对77例广西南部，北部地区人群HBV无症状携带者血清HBV前C区进行扩增，阳性者用直接测序法进行序列分析。结果 39例HBsAg无症状携带者血清HBVDNA阳性，阳性率为50.7%(39/77)，突变株出现率为22.1%(17/77)。南部地区阳性率为55.6%(20/36)，其中6份标本出现突变株，占30%，常见的突变类型是nt1858位发生点突变（T→C),只有一份标本在nt1896发生点突变（G→A），导致终止密码产生，该标本同时伴有nt1837点突变（A→G）；北部地区阳性率为46.3%(19/41)，其中有11份标本出现突变株，占57.9%,常见的突变类型是ny1896位发生点突变（G→A），这些标本中有4份同时在nt1846发生点突变（A→T），2份同时在nt1862发生点突变（G→T)；标本734分别在nt1856,1858发生点突变（C→T，T→C）。结论 广西地区HBV无症状携带者HBV前C区突变株的流行率居全国中等水平，广西南部，北部是否存在主要突变类型不同值得进一步研究。     

Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya

Hepatitis B virus (HBV) genotypes are important in both the clinical manifestation of disease and treatment response. Although Kenya belongs to the African Region (AFR-E) characterized by high mortality and hyperendemicity of HBV, there is a paucity of HBV genotyping data. The aim of this study was to molecularly characterize the basic core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads were determined. HBV DNA was amplified and sequenced from 58/61 patients. In addition to the complete genome of two isolates, the BCP/PC and the complete S regions of 43 and 38 isolates, respectively were sequenced. Following phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1, whereas two isolates clustered with genotype D, one with subgenotype D1 and another as an outlier of the clade containing subgenotype D6 and the D/E recombinant. When the complete genome of the latter isolate was sequenced it clustered with D6. The majority of isolates belonged to serological subtype adw2 and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by different amino acid motifs, circulate in Kenya: two in the African cluster and a monophyletic clade in the “Asian” cluster. HBeAg-negativity was a result of G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity was a result of mutations in the Kozak region (1809–1812) or precore start codon (1814–1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC patients (p < 0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver disease patients in Kenya, with A1 predominating.     

High circulation of hepatitis B virus (HBV) precore mutants in Tunisia, North Africa

Hepatitis B Virus (HBV) e antigen (HBeAg), HBV DNA and precore mutations affecting HBeAg expression during active replication were studied in 72 Tunisian hepatitis B surface antigen (HBsAg) positive individuals: 30 asymptomatic carriers of the virus, 37 with chronic hepatitis and 5 with acute hepatitis. HBV DNA was detected in 44 patients, but only 20% of them expressed HBeAg. Precore mutant strains, with mutations at position 1896 or at positions 1896 and 1899, were detected by PCR-hybridization in 86 and 36% of patients, respectively. Wild-type strains were detected in 54% of patients. Precore mutants were found in chronically and in acutely infected individuals, in patients with severe and asymptomatic infections, in HBeAg positive as well as HBeAg negative individuals.These results show the high frequency of HBV precore mutants in Tunisia.     

Nosocomial transmission of hepatitis B virus infection through multiple-dose vials.

The source of acute hepatitis B virus (HBV) infection in two women (55 and 72 years old) was investigated. They displayed no risk factors for acquiring HBV infection, other than treatment with local anaesthetic injections some months previously. The HBV strains were sequenced and showed distinct homology to strains seen in Swedish intravenous drug users (IVDU). Prior to these patients' acute infection, an outbreak of HBV had occurred among IVDU in the same county. Analysis of the HBV strains from six of these IVDUs showed their core promoter, precore and pre-S sequences (679 nucleotides) to be identical to those from the two patients. Cross-contamination between samples was excluded and the most likely source of infection was thought to be multiple-dose vials of local anaesthetic that had been contaminated with the HBV strain circulating among the IVDU population in the community. We believe that multiple-dose vials have no place in modern healthcare and recommend sequence homology analysis as an alternative or additional way to trace a source of HBV infection.     

Hepatitis delta virus infection in Bombay.

From June 1985 to June 1989, sera from 425 cases of acute viral hepatitis were gathered from 2 hospitals in Bombay; 331 sera were positive for hepatitis B surface antigen and immunoglobulin M anti-hepatitis B core antigen, and the donors' disease was diagnosed as hepatitis B. Anti-hepatitis D virus was found in 124 of these sera, and hepatitis D antigen was present in 24 more, conclusively proving the presence of hepatitis delta infection in association with hepatitis B in Bombay. Among the 425 cases of hepatitis, 39 cases of fulminant hepatitis developed, of whom 31 died. Hepatitis B virus (HBV) was the apparent viral infection in 32 of the fulminant cases, and 20 (63%) of them also showed evidence of hepatitis D virus (HDV) infection, suggesting an aggravation of their clinical course due to concurrent HBV and HDV infections.