肝炎病毒指南

Medicine fnternationaI ·Liver Disorders· A Guide to the Hepatitis T 7 ● v lruses A J Zuckerman Viral hepatitis is a major public health problem through— out the world． affecting several hundred million individ— uals． It CaLISON considerable niorbidity alld nlol talhy from bo th acute infection and chronic sequelae including chronic hepatitis， cirrhosis and primary liver cancer． Hepatocellular carcin()ITIg is one of the ten nlost common cancers WOI·ldwide． The he1)atitis virUSeS are a range of unrelated and of— ten highly llllllSl tal human pathogens． Ilepatitis A virus(ItAV)i8 a small，non—envelo1)ed， Sylllnlet1．ical I NA virus with many characterislics of the picornavirus fainily． fhis virus has been classified as hepatovirus， wlthin tile heparnavirus genus． It causes infeetious or epidemic hepatitis transmitted by the faecal— eral route． HAV continues to be endemic throughout the world and hyperendemic in regions with lx)or stan— dards of sanitation and hygiene． The seroprevalence of antibodies to HAV has decreased since W orld W ar I I in many industrialized countries， but large epidemics may still occur；for example， an outbreak of hepati tis A as— sociated with tile consumption of clams in Shanghai， China in l 988 resulted in almost 300．000 cases． Hepatitis B virus(ttBV)is a member of the hepad— navirus group — double—stranded I) A viruses which replicae bv re'vrerse transcription． HBV is endemic in the hunian 1)opulation and hyperendemic in many parts of the world． HBV was origi nally recognized as the agent resFonsi— ble for ‘serum hepati tis’． the most common form of parenterally transmitted viral hepatitis， and an impor— tant cause of acute and chronic infection of the liver．A— cute hepatitis B is often anicteric and asymptomatic， though a severe illness with iaundice can Occur and OCCa— sionally acute liver failure develops． Persistent carriage of HBV (defined by the presence of hepatitis B surface antigen， HBsAg， in the serum for more tlK．n 6 months)has been estimated to affect about AJ Zuckerman is Prinapal and Dean of the RoyaI Free,and University College Medical School， London，UK M日 I Cl 49 350 million individuals worldwide．Ixmg—term continu— ing virus replication may result in cirrhosis and hepato— cellular carci noma． 1tepatitis C virus(HCV)is an enveloped single—stranded I A virus which seems to be distantly related to fla— viviruses． Infection is common in many countries； it is ass)elated with chronic liver disease and primary liver cal1CeI． W hen diagnostic tests for HAV and HBV became available(in I973—5 and I969—70，respectively)，it was SOOll apparent that most cases of IX)St—transfusion hepatitis were not caused by either of these agents，or by other known hepatotropic viruses． Fransmission 【udics i1I L liiiIIlj IIIZCCN c 【；Ibli,41c~1 that the nlaill agent of 1)al enterally ac(tuired non—A．ROll—Ij hepatitis was likely to 1)e an enveloped virus alx)ut 30—60 llm in diameter． fhcse studies nlade available a I)ooI of plasma containing a relatively high thre of the agent． fo clone the genome，the virus was pelleted from the plasma and denalul。ed㈨ that either I) A or RNA COtlld se1．ve as a tenolate (as it was unknown whether the genome was I) A Ol·It A)，and cI) A was synthe— sized． I"tlo resuhant cI)NA was illSel。ted into the bacte— riophage expression vector lamM a gt ll and the libraries were screened using serulll from a patient with chronic non—A．non—Ij lle1)atitis． l'his approach led to the de— tection of a clone(designated 5 l—1)with an antigenic compone rit which bound to antilx)dies present in the sera of several individuals with non—A． non—B hepatitis． fhis clone was used as a 1)l·obe to detect a larger，over— lapping clone in the saino lil)rary． Fhese Sequence hy— I)ridized to a posi tive—sense I A molecule about l 0，000 nucleotides ii1 length fOtllld only in the livers of infected chimpanzees． No homologous Xxluenees could be detect— ed in the chim1)anzee or l1UI1lan genomes． Using a ‘walking’technique， newly detected overlapping clones could be used as llybridization 1)l obes in turn．to detect further viFUS—specific clones in lllc librarv． I'hus．clones covering lIle elltll e viral geilonle were ultimately asbelll— I)led and ll1c com1)lete nucleotide sequence of HCV was detern1ined． Hepatitis D(delta)virus(HDV)i8 an unusual single— stranded， circular RNA virus；its genomic structure is siniilar to certain plant viral satellites and viroids． It re— uLlil·es a hel1)er function of HIjV for transmission； HDV is coated with HBsAg． HI)V infection does not persist in the absence of HBV infection． I)elta hepatitis is common in some regions where there is a high prevalence of HBV infection， particularly M editerranean countries，parts of Eastern Europe． the M iddle East． Afrlca and South Amerlca． It has been estimated that 5％ of HBsAg carriers worldwide(about 0 2000 The Medicine Publishing Company Ltd 维普资讯 http://www.cqvip.com Medicine InternationaI 15 million individuals)are infected with HDV．In areas of lOW HBV prevalence， those at risk of hepatitis B， particularly intravenous drug abusers， are also at risk of HDV infection．HDV iS an important cause of acute and severe chronic liver damage， particularly in some re— gions． Hepatitis E virus (HEV)：retrospective testing of serUlTI samples from patients involved in hepatitis epi— demics associated with contamination of water supplies with human faeces indicated that an agent other than HAY (or HBV)was involved．Epidemics of enterically transmi tted non—A， non—B hepatitis were first reported M日)JCINE in 1980 in the Indian subcontinent．but outbreaks in— volving tens of thousands of Cases have been dcum ented in the former USSR，South East Asia，Northern Africa and M exico ． The agent respo nsible for enteric．ally transmi tted non- A，non—B hepatitis is HEV， a non-enveloped ， single— stran ded RNA virus with biophysical an d biochemical features of the caliciviruses． It produces a self—limiting disease resembling hepatitis A，but has a high mortality rate in pregnant women during the third trimester． Chronic liver disease and persistent viraemia have not been observed． ◆ o 2000 The Medicine Publishing Company Lt~l 维普资讯 http://www.cqvip.com 国际内科双语杂志 2001，Voi．1，No．2 肝炎病毒指南 ·肝脏疾病 · 肝炎病毒指南 A J ZuckermanO MEDICINE，1999，27(1)：30 病毒性肝炎是一个重要的世界性公共卫生问， 有几亿人受累。其急性感染以及慢性后遗症 (包括慢 性肝炎、肝硬化和原发性肝癌)的发生率和死亡率都 相当高。肝细胞癌是世界上 10种最常见癌症之一。 肝炎病毒是一系列互不相关的、非常独特的人类 病原体。 甲型肝炎病毒 (HAV) HAV是一种无包膜、对称的微小 RNA病毒，具 有微小核糖核酸病毒科的许多特征。本病毒已归类为 肝病毒，属于肝 RNA病毒属。它经粪 一口途径传播， 引起传染性或流行性肝炎。HAV仍在世界上许多地 方流行，卫生条件差的地区高发。第二次世界大战 后，很多工业化国家抗 HAV抗体的血清阳性率已经 降低，但大规模流行仍可能发生，例如 1988年在中 国上海由于食用蛤类引起甲肝暴发，造成近 30万人 发病。 乙型肝炎病毒 (HBV) HBV是肝DNA病毒的一员。这类病毒是通过反 转录复制的双链 DNA病毒。HBV在人群中流行，在 世界上很多地区高发。 HBV最初被当作引起 “血清性肝炎”的病原体， 这种肝炎是非消化道传播的病毒性肝炎中最常见的类 型，也是肝脏急、慢性感染的重要病因。急性乙型肝 炎常常无黄疸和无症状，但严重时也可伴有黄疸，偶 尔发生急性肝衰竭。 据估计全世界约有 3．5亿人持续携带 HBV [定义 为血清中乙肝面抗原 (HgsAg)存在超过 6个月]。 长期不断的病毒复制可导致肝硬化和肝细胞癌。 ①A J Zuc~rman是英国伦敦皇家自由大学校长和皇家 自由大学医 学院院长。 51 丙型肝炎病毒 (HCV) HCV是一种有包膜的单链 RNA病毒，似乎与黄 病毒有关联。HCV感染在很多国家常见，与慢性肝 病及原发性肝癌有关。 随着 HAV和 HBV诊断性试验的问世 (分别在 1973年～1975年和 1969年～1970年)，很快发现大 多数输血后肝炎病例不是由这两种病原体引起的，也 不是由其他已知的亲肝病毒引起的。用黑猩猩进行的 传播研究证实这种非消化道感染的非甲、非乙型肝炎 的主要病原体很可能是一种直径 30～60nm 的有包膜 的病毒。通过这些研究获得了大量相对高滴度的含有 这种病原体的血浆。 为了克隆其基因组，将病毒从血浆中分离浓缩， 使其变性以使 DNA或 RNA可以作为模板 (因为不知 道基因组是DNA还是RNA)，然后合成 eDNA。将合 成的 eDNA插入噬菌体表达载体 tl1，然后用慢性 非甲、非乙型肝炎病人血清筛查基因库。用这种 检测到一个克隆 (命名为 5—1—1)，其抗原成分可与 一 些非甲、非乙型肝炎病人血清中存在的抗体结合。 这个克隆可作为探针在同一基因库检测更大的、重叠 的克隆。将这些序列杂交到仅存在于受感染黑猩猩肝 脏的、长约 10 000个核苷酸的正义 RNA分子。在黑 猩猩或人类基因组中都不能检测到同源序列。利用 “走步”技术，新检测到的重叠克隆可反过来用作杂 交探针，在基因库中进一步检测病毒特异性克隆。这 样，包括整个病毒基因组的克隆最终被完成，HCV 的全部核苷酸序列得以确定。 丁型肝炎病毒 (I-IDV) HDV是一种不寻常的单链环状 RNA病毒，其基 因组结构与某些植物病毒随体或类病毒相似。HDV 的传播需要HBV的帮助；HDV被HgsAg包裹。没有 维普资讯 http://www.cqvip.com 肝炎病毒指南 HBV感染，HI)V感染就不持久。 丁型肝炎常见于某些 HHV感染高发地区，特别 是在地巾海冈家、尔欧部分地区、中东、J 洲卡¨南美 洲。据估计 Il上界仃 5 的 HBsAg携带者 (大约 15 000 000人)被 HI)V感染。在 HBV低发地 ，乙 肝炎易感人群 (特别足静脉吸毒者)也足 HI)V的 易感人群。HI)V住某螳地区是急性和严重慢性肝损 伤的重要病 。 戊型肝炎病毒 (flEV) 埘人炎污染水源引起的传染性肝炎病人血清标本 的同顺性 榆验 示有一种 属 HAV (或 HHV)的病 国际内科双语杂志 2001，Vo1．1，No．2 52 原体。1980年在印度次大陆首次报道了经消化道传播 的非甲、非乙型肝炎的流行，但此前在前苏联、东南 亚、北非和墨西哥已有数万病例发病的。 引起经消化道传播的非甲、非乙型肝炎的病原体 足 I-D2V。这是一种无包膜的单链 RNA病毒，具有杯 状病毒的生物物理学和生物化学特征。戊型肝炎具有 白限性，这 与甲型肝炎类似，但戊型肝炎在妇女妊娠 末的三个月死亡率很高。尚未观察到戊型肝炎引起的 慢性肝病和持久的病毒血症。 (孙 钢译 顾瑞金校) 维普资讯 http://www.cqvip.com