Posttransfusion hepatitis type A

Hepatitis A virus (HAV) transmission through blood is a rare but potential cause of posttransfusion hepatitis. We can now document such a case supported by laboratory evidence of HAV in the donor blood. A 10-year-old girl manifested icteric hepatitis A 31 days after receiving a single unit of packed RBCs from a donor who subsequently experienced hepatitis A and died in hepatic failure. Hepatitis A virus antigen was detected in the donor's hepatocytes and in plasma obtained from the original donor unit. The density in cesium chloride of the HAV antigenic activity from the liver and plasma ranged from 1.33 to 1.37 g/cu cm, which is similar to that reported for infectious HAV particles. The implicated donor plasma had normal aminotransferase levels and was negative for antibody to HAV. Inoculation of this plasma into a chimpanzee resulted in the development of hepatitis A 23 days later based on the appearance of fecal HAV antigen, hepatitis, and IgM anti-HAV seroconversion. These data clearly document the presence of HAV in the donor sample that produced posttransfusion hepatitis A.     

甲型肝炎早期实验诊断的研究

以人胚肺二倍体细胞分离出的甲型肝炎病毒作抗原,以马抗人IgM经纯化后的抗体为捕捉抗体,以纯化甲型肝炎恢复血清为特异性抗体,过碘酸钠法标记酶,以OPD为底物制成抗-HAV IgM诊断试剂盒,建立了ELISA捕捉法检测抗-HAV IgM,结果:甲型肝炎暴发点84例均为阳性,流行性出血热及健康成人各30例均为阴性。322例急性黄疸型肝炎住院患者中192例阳性(占59.6%)。12例第一病日患者11例阳性(占91.6%),证明该方法对甲型肝炎早期诊断有重要价值。     

HAV，HBV与HCV感染相互关系的研究

目的　探讨甲乙丙三型肝炎病毒感染的相互关系。方法　应用国产试剂盒 ,采用EIA法对 515例肝炎患者的血清标本同时测定了甲乙丙三型肝炎病毒感染的血清学标志。结果　在抗 -HAVIgM阳性和阴性者之间 ,HBsAg、HBeAg阳性率无显著差异 ;HBsAg阳性者的抗 -HAVIgM阳性率和抗 -HCV阳性率显著低于HBsAg阴性者 (分别为 4 .0 %对 2 3.5%和 3.4 %对 2 4 .2 % ,P <0 .0 0 0 1) ;HBeAg阳性者的抗 -HCV阳性率明显低于阴性者 ( 1.3%对 14.0 % ,P <0 .0 0 0 1) ;抗 -HCV阳性者的HBeAg阳性率明显低于抗 -HCV阴性者 ( 9.6%对 32 .8% ,P <0 .0 1)。结论　HBV复制与HCV感染之间可能存在一定的交互抑制作用     

ETIOLOGY OF TYPE A HEPATITIS

Particles closely resembling hepatitis A virus (HAV) are isolated from 6 0f 10 patients studied and high titered anti-HAV serum is produced which is interesting and may be of practical importance for diagnosis purposes. Further studies for more definite identification of the particles is being persued.     

重型病毒性肝炎的血清病原学研究

为了解重型病毒性肝炎（重肝）的病原分型及其与预后的关系，应用酶联免疫法对120例重肝患者进行了甲型肝炎病毒抗体（抗-HAV）IgM、HBV标志（HBVM）、丙型肝炎病毒抗体（抗-HCV）的检测。结果显示：抗HAV－IgM阳性19例（15．8％）；HBVM阳性90例（75．0％）；抗-HCV阳性29例（24．2％），其中19例合并HBV感染，单纯抗-HCV阳性6例；三型病毒标志阴性者16例（13．3％）。乙型重肝较甲型重肝、丙型重肝病死率高。慢性重肝、急性重肝较亚急性重肝预后差。HBV复制标志阳性患者预后较差。提示HBV是本地区重肝的主要病原，且预后较差。     

甲/戊型肝炎重组抗原的表达、纯化及与传统甲肝疫苗免疫原性的比较

目的比较基因工程重组抗原与传统疫苗的免疫原性;探讨同一载体表达不同抗原的能力和抗原间的相互作用。方法将编码甲型肝炎病毒Vp1aa24-171和戊型肝炎病毒ORF2aa431-615的重组表达质粒pBV220-EAAg342及pBV220-AEAg342转化入大肠杆菌BL-21,筛选出高效表达的菌种进行目的蛋白的表达。用DEAE-sepharose FF和CM-sepharoseFF离子层析交换柱纯化表达重组蛋白,采用SDS-PAGE、Western blotting方法进行分析鉴定。用纯化的重组蛋白及传统甲肝疫苗灭活疫苗与减毒活疫苗免疫小鼠,比较特异性抗体的产生水平。结果表达的重组蛋白相对分子质量约为36000,表达量约占菌体总量的25%;且重组嵌合抗原EAAg342可以形成直径10～20nm的类病毒(virus-like particles,VLP)颗粒。Western blotting证实2种重组蛋白均能分别与甲型肝炎和戊型肝炎患者阳性血清发生特异性反应。免疫小鼠后可诱导产生高滴度的抗戊肝特异性抗体;而抗甲肝特异性抗体水平与传统甲肝疫苗相比较低。结论使用原核系统表达的甲/戊肝重组抗原能够高效表达,2种不同的融合蛋白均分别具有良好的抗原性和免疫原性,具有开发双价疫苗及同时诊断甲型戊型肝炎试剂盒的前景。     

TIM-1 和TIM-4 mRNA 在HAV 患者中的表达及其临床意义

目的 观察典型病程甲型病毒性肝炎（HAV）患者外周血中T 细胞免疫球蛋白域蛋白-1 （TIM-1）和T 细胞免疫球蛋白域蛋白-4（TIM-4）mRNA 的表达水平,探讨HAV 患者病情进展的不同时 期TIM-1 和TIM-4 mRNA 水平与HAV RNA 含量,HAV 免疫球蛋白M（IgM）、免疫球蛋白G（IgG）浓度 及肝功能指标的关系。方法 选取HAV 典型病程的30 例患者作为HAV 组,分别于潜伏期或黄疸前期、黄 疸期及恢复期留取血液标本,以同期30 例健康体检者作为对照组,收集血液标本。采用实时荧光定量聚合 酶链反应检测TIM-1 和TIM-4 mRNA 表达水平,同时检测HAV 患者外周血HAV RNA 含量,酶联免疫 吸附法检测HAV 患者外周血HAV 抗体IgM、IgG 滴度水平,全自动生化分析仪检测肝功能指标谷丙转氨 酶、谷草转氨酶及总胆红素。结果 HAV 组患者外周血TIM-1 和TIM-4 mRNA 表达水平高于对照组患者 （P <0.05）。随着疾病进程的继续,TIM-1 及TIM-4 mRNA 表达水平于黄疸期达峰值,恢复期下降。TIM- 1 mRNA 表达水平与HAV 患者IgM 滴度、AST 及TBIL 呈正相关（P <0.05）,与IgG 滴度无关（P >0.05）。 结论 HAV 患者外周血中TIM-1 和TIM-4 mRNA 的表达水平与HAV 的疾病进展有较好的拟合性,TIM-1 和TIM-4 mRNA 可能在HAV 的发生、发展中发挥作用。     

以RFIL消除慢性乙型肝炎血清RF致的抗HAV-IgM假阳性反应

为了解HAV/HBV双重感染的发生情况,作者检测了121例慢性乙型肝炎患者血清抗HAV-IgM,其中经类风湿因子免疫胶乳(RFIL)处理后抗HAV-IgM仍阳性的7例,未经处理的12例阳性,有5例为假阳性,占41.7％(5/12)。用RFIL能消除因血清中RF所致的抗HAV-IgM假阳性反应,不出现假阴性结果。认为RFIL中和反应是一种简单,经济而有效的排除RF干扰的方法。本组慢性乙型肝炎患者重叠感染甲肝病毒7例,占5.8％,均为慢性活动性肝炎。     

甲型肝炎减毒活疫苗病毒的水平传播

目的 探讨甲型肝炎（甲肝）减毒活疫功接种后的病毒水平传播。方法 在昆明市安宁县2个观察点筛选出丙氨酸转氨酶（ALT）正常、甲肝（HAV）抗体（抗－HAV）阴性的4－7岁儿童199人,按1：1.4比例分接种组（82人）和接触组（117人）进行H2株甲肝减毒活疫苗病毒的水平传播观察;另外,取接种者和接触者HAV检测阳性的粪便悬液上清,分别静脉接种于8普通狨猴（Callithrix jacchus）体内,观察粪便HAV毒力水平。结果 接种组接种后6周抗体阳转率为97.6％（80／82）,接触组9周时抗体阳转率为13.7％（16／117）,两组儿童肝功能均未见异常 种组和接触组的粪便HAV检出率分别为89.5%(34/38)和70.7%(53/75）;以2株接种者粪便HAV和2株接触者粪便HAV感染的8只狨猴,均未检出血清酶升高和肝脏组织病理学改变,抗－HAV和2株接触者粪便HAV感染的8只狨猴,均未检出血清酶升高和肝脏组织病理学改变,抗－HAV阳转时间延迟且效价低。结论 H2株甲肝减毒活安全性及免疫原笥良好,疫苗病毒在人体内增殖活跃,且保持减毒性能稳定,能在人群中造成水平传播,但不会引发甲肝。     

189例急性病毒性肝炎患者的血清学调查

目的研究我国部分地区189例急性病毒性肝炎患者5种病毒性肝炎的分型构成。方法用酶免疫法(EIA)检测2007-2008年吉林(59例)、河北(54例)、山东(28例)、江苏(28例)、新疆(20例)等地急性病毒性肝炎门诊及住院的189例患者抗-HAV IgM、抗-HBc IgM、抗-HCV IgM、抗-HDV IgM和抗-HEV IgM。结果 189例急性病毒性肝炎患者甲型肝炎(HA)7例(3.70%),乙型肝炎(HB)65例(34.39%),丙型肝炎(HC)17例(8.99%),戊型肝炎(HE)71例(37.57%),未分型肝炎11例(5.82%),重叠感染18例(9.53%)。重叠感染以HBV/HEV常见。甲、乙、丙、戊及未分型肝炎患者的平均发病年龄分别为39.43、36.42、45.23、50.24及32.91岁。各型肝炎男女性发病比为1.83∶1~6.00∶1。结论在本研究群体中HBV和HEV是急性散发性病毒性肝炎最主要的病原体。各型急性病毒性肝炎男女性发病性别比均为男性多于女性,平均发病年龄与以往相比有后移现象,其中HE最为明显,集中在中老年人群。     

Safety observation of attenuated live hepatitis B vaccine (H2 strain) in humans

3089 healthy persons, aged 4 to 27 years, have been inoculated in 3 batches with attenuated live hepatitis A vaccine (H2 strain) since May, 1987. Each subject received 10(8.5) TCID dosage subcutaneously in the upper arm. None of the recipients developed any local or systemic reaction during a 42-day followup after vaccination. The serum enzyme activities, including SGPT/ALT and LDH5, were within normal range during the 4th to 16th weeks of serial tests after inoculation. The study of hepatitis A virus (HAV) shedding in feces of 4 subjects showed that no hepatitis A antigen (HAAg) was detected with antigen capture ELISA, but infectious HAV was recovered from stool-cell cultures in three of four recipients. No patient with hepatitis A was found within 6 months after vaccination in the institution where the HAV vaccine was used. In addition, no immunological evidence was seen that the HAV vaccine recipients can transmit HAV after the investigation of serological epidemiology at a class in which the HAV vaccine was tested. It is suggested that the potential of hepatitis A related to HAV vaccine among the non-vaccinated persons is rare. Seroconversion occurred at a mean time of 2 to 5 weeks after inoculation, and the positive rate of specific antibody was 95.6%.     

Revisiting the Holy Cross football team hepatitis outbreak (1969) by serological analysis

Clinical and biochemical data collected during the Holy Cross College football team hepatitis A outbreak in 1969 suggested that 32 team members had icteric hepatitis, 58 had anicteric illness, and only seven were not infected. Using a currently available radioimmunoassay, we tested stored serum samples obtained during the outbreak for IgM antibody to hepatitis A virus (IgM anti-HAV). Only individuals with icteric hepatitis were found to have IgM anti-HAV in serum; those with presumed anicteric illness were shown not to be infected with hepatitis A virus. The attack rate was thus only 34%, not 93% as originally reported, and the incidence of icteric illness in those infected was 100%, not 33%. This serological analysis of a classic outbreak of hepatitis A illustrates the utility and importance of IgM anti-HAV testing in seroepidemiologic investigations of hepatitis outbreaks.     

Pancreatitis following hepatitis A vaccination

We describe a 23-year-old male patient who presented with epigastric abdominal pain, 8 days following vaccination with inactivated hepatitis A virus (Haverix(R)). Clinical and laboratory data confirmed the diagnosis of pancreatitis. Repeat polymerase chain reaction (PCR) for hepatitis A replication was negative. A comprehensive evaluation ruled out other etiologies for pancreatitis. IgM Hepatitis A antibodies did not develop even after 3 months. Pancreatitis following Hepatitis A is a well-known complication of the viremia, but the exact mechanism is controversial. We suggest that the pancreatitis may have been a cellular immunlogical reaction to one of the antigens of hepatitis A virus vaccine, or it might have been caused by the release of mediators of anaphylaxis such as histamine and leucotriens, induced by HAV antigens, resulting in pancreatitis without development of humoral immunization.     

肿瘤坏死因子（TNF）对流行性出血热,甲型肝炎病毒的作用研究

流行性出血热和甲型肝炎严重危害人民健康。目前对流行性出血热病毒和甲肝病毒还暂无特效药物,近年报道肿瘤坏死因子具有抗病毒活性,本文报告用在国内分离、克隆并表达的人重组肿瘤坏死因子(rhTNF-2)在体外对流行性出血热病毒及甲型肝炎病毒的抗感染作用进行了研究,现将结果报告如下。材料与方法     

病毒性肝炎抗平滑肌抗体的初步研究

本文报告用间接免疫荧光试验(IFL)测定200例病毒性肝炎患者血清抗平滑肌自身抗体(SMA)的结果。分析表明:甲型肝炎病毒(HAV)无论是单纯感染或是与乙型肝炎病毒(HBV)合并感染、患者血清SMA的阳性率均较HBV感染时高(P<0.005),而且与HBV复制受抑制相关。HAV感染后可抑制HBV的复制,可能因患者血清中曾存在循环干扰素(IFN),鉴于这种HAV与HBV之间的病毒干扰现象,作者提出,定期多次应用甲肝疫苗或其它药物不断诱生IFN,有可能为乙型肝炎的治疗开辟新的途径。     

急性病毒性肝炎中肝炎病毒的多重感染

在243例急性黄疸型肝炎患者中发现肝炎病毒多重感染者77例(31.69％),包括HAV+HBV双重感染65例,HBV+HDV协同感染4例,HAV+HBV+HDV三重感染7例,HBV+CMV重叠感染1例。多重或单一病毒感染组其SB和SGPT升高的水平差异无显著性,但肝炎病毒多重感染与甲或乙型急性肝炎相比,其黄疸消退和SGPT恢复时间均明显延长。     

毛蚶传播甲型肝炎的病原学证据——核酸分子杂交和免疫电镜初步结果

本文应用cDNA-RNA分子杂交技术和免疫电镜法,检测上海市1988年初甲型肝炎(甲肝)流行期前的市售毛蚶。将毛蚶鳃和消化腺研碎,经酚-氯仿提取和乙醇沉淀法提取RNA,用~(32)P标记的pHAV(LB) 228甲肝病毒cDNA探针进行杂交。从7份毛蚶样品中检出一份甲肝病毒RNA阳性。另外将毛蚶鳃和消化腺的粗制悬液与甲肝病人恢复期血清孵育后电镜观察,看到形态大小一致的成堆病毒样颗粒,直径约为27mm,与甲肝病人粪便样品中所见病毒样颗粒相似。在7份毛蚶样品中还见到几种不同形态颗粒,大的病毒样颗粒直径可达45mm。     

ELISA检测血清戊型肝炎病毒IgM型抗体

用ＥＬＩＳＡ检测血清抗ＨＥＶ－ＩｇＭ。３０份抗ＨＥＶ－ＩｇＧ阳性急性肝炎患者血清中，抗ＨＥＶ－ＩｇＭ阳性１３份，阳性率４３．３％。抗ＨＥＶ－ＩｇＭ阳性结果可被加入的ＤＴＴ所阻断，但不受ＨＡＡｇ，ＨＢｃＡｓ或ＨＢｅＡｇ的影响。因此抗ＨＥＶ－ＩｇＭ的特异性较高，对戊型病毒性肝炎的诊断有一定价值。     

恒河猴猴群中甲型肝炎病毒(HAV)血清学调查

用EUSA法对183份来自不同饲养条件下各年龄阶段的自繁猴血清进行了甲型肝炎病毒抗体(HAVIgG)的检测,阳性率为68．9％,其中单笼猴抗-HAV阳性率明显低于大笼猴及群养猴,并随年龄的增长而升高。同时对41只野生猴进行检测,阳性率为19．5％,明显低于自繁猴,这一结果为恒河猴的饲养管理提供依据。     

Use of IgM-hepatitis A antibody testing. Investigating a common-source, food borne outbreak

An outbreak of hepatitis, type A, affecting 30 employees of a large metropolitan department store was investigated using traditional case findings, a food preference questionnaire, and case-control methods. In addition, the new serological tests for IgM and IgG antibody to hepatitis A virus (anti-HAV) were employed to establish a serological diagnosis of hepatitis A infection, to define the control group, and to identify the index case, an asymptomatic food handler. Twenty-five of 25 cases tested had IgM anti-HAV, whereas none of 73 controls and one of 46 food handlers were IgM anti-HAV positive. This test eliminated three suspect cases that were diagnosed as hepatitis but that had atypical epidemiologic features. Epidemiologic and serological analysis confirmed the association of illness with eating in the employees' cafeteria and eating cold sandwiches.