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a harmful or corrupting agency; "bigotry is a virus that must not be allowed to spread"; "the virus of jealousy is latent in everyone"
(virology) ultramicroscopic infectious agent that replicates itself only within cells of living hosts; many are pathogenic; a piece of nucleic acid (DNA or RNA) wrapped in a thin coat of protein
a software program capable of reproducing itself and usually capable of causing great harm to files or other programs on the same computer; "a true virus cannot spread to another computer without human assistance" (同)computer virus
the 2nd letter of the Roman alphabet (同)b
the blood group whose red cells carry the B antigen (同)type_B, group B
inflammation of the liver caused by a virus or a toxin

PrepTutorEJDIC

ビールス,ろ過性病原体
肝[臓]炎

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/17 12:55:37」(JST)

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For the disease, see Hepatitis B.

Hepatitis B virus, abbreviated HBV, is a species of the genus Orthohepadnavirus, which is likewise a part of the Hepadnaviridae family of viruses.^[1] This virus causes the disease hepatitis B.^[2]

Disease[edit]

Main article: Hepatitis B

In addition to causing hepatitis, infection with HBV can lead to cirrhosis and hepatocellular carcinoma.^[3]

It has also been suggested that it may increase the risk of pancreatic cancer.^[2]

Classification[edit]

The hepatitis B virus is classified as the type species of the Orthohepadnavirus, which contains three other species: the Ground squirrel hepatitis virus, Woodchuck hepatitis virus, and the Woolly monkey hepatitis B virus. The genus is classified as part of the Hepadnaviridae family, which contains two other genera, the Avihepadnavirus and a second which has yet to be assigned. This family of viruses have not been assigned to a viral order.^[4] Viruses similar to hepatitis B have been found in all the Old World apes (orangutan, gibbons, gorillas and chimpanzees) and from a New World woolly monkey suggesting an ancient origin for this virus in primates.

The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes present on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination.^[5]^[6]

Unclassified species[edit]

A number of as yet unclassified Heptitis B like species have been isolated from bats.^[7]

Morphology[edit]

Structure[edit]

The structure of hepatitis B virus

Hepatitis B virus is a member of the Hepadnavirus family.^[8] The virus particle, (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses.^[9] The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.^[10]

Components[edit]

It consists of:

HBsAg
HBcAg (HBeAg is a splice variant)
Hepatitis B virus DNA polymerase
HBx. The function of this protein is not yet well known,^[11] but evidence suggests it plays a part in the activation of the viral transcription process.^[12]

Hepatitis D virus requires HBV envelope particles to become virulent.^[13]

Evolution[edit]

The early evolution of the Hepatitis B, like that of all viruses, is difficult to establish.

The divergence of orthohepadnavirus and avihepadnavirus occurred ~125,000 years ago (95% interval 78,297–313,500).^[14] Both the Avihepadnavirus and Orthohepadna viruses began to diversify about 25,000 years ago.^[14] The branching at this time lead to the emergence of the Orthohepadna genotypes A-H. Human strains have a most recent common ancestor dating back to 7,000 (95% interval: 5,287–9,270) to 10,000 (95% interval: 6,305–16,681) years ago.

The Avihepadnavirus lack a X protein but a vestigial X reading frame is present in the genome of duck hepadnavirus.^[15] The X protein may have evolved from a DNA glycosylase.

The rate of nonsynonymous mutations in this virus has been estimated to be about 2×10⁻⁵ amino acid replacements per site per year.^[16] The mean number of nucleotide substitutions/site/year is ~7.9 x 10^-5.

A second estimate of the origin of this virus suggests a most recent common ancestor of the human strains evolved ~1500 years ago.^[17] The most recent common ancestor of the avian strains was placed at 6000 years ago. The mutation rate was estimated to be ~10^-6 substitutions/site/year.

Genome[edit]

The genome organisation of HBV. The genes overlap.

Size[edit]

The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full length strand) and 1700–2800 nucleotides long (for the short length strand).^[18]

Encoding[edit]

The negative-sense, (non-coding), is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand. Non-coding bases are removed from the ends of the (-)sense strand and the ends are rejoined.

There are four known genes encoded by the genome called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced.^[19] The function of the protein coded for by gene X is not fully understood.^[20]

Several non-coding RNA elements have been identified in the HBV genome. These include: HBV PREalpha, HBV PREbeta and HBV RNA encapsidation signal epsilon.^[21]^[22]

Genotypes[edit]

There are eight known genotypes labeled A through H.^[5] A possible new "I" genotype has been described,^[23] but acceptance of this notation is not universal.^[24] Different genotypes may respond to treatment in different ways.^[25]^[26]

The genotypes differ by at least 8% of the sequence and have distinct geographical distributions and this has been associated with anthropological history. Type F which diverges from the other genomes by 14% is the most divergent type known. Type A is prevalent in Europe, Africa and South-east Asia, including the Philippines. Type B and C are predominant in Asia; type D is common in the Mediterranean area, the Middle East and India; type E is localized in sub-Saharan Africa; type F (or H) is restricted to Central and South America. Type G has been found in France and Germany. Genotypes A, D and F are predominant in Brazil and all genotypes occur in the United States with frequencies dependent on ethnicity.

The E and F strains appear to have originated in aboriginal populations of Africa and the New World, respectively.

Within genotypes 24 subtypes have been described which differ by 4-8% of the genome.

Type A has two subtypes: Aa (A1) in Africa/Asia and the Philippines and Ae (A2) in Europe/United States.

Type B has two distinct geographical distributions: Bj/B1 ('j' — Japan) and Ba/B2 ('a' — Asia). Type Ba has been further subdivided into four clades (B2 — B4).

Type C has two geographically subtypes: Cs (C1) in South-east Asia and Ce (C2) in East Asia. The C subtypes have been divided into five clades (C1 — C5). A sixth clade (C6) has been described in the Philippines but only in one isolate to date.^[27] Type C1 is associated with Vietnam, Myanmar and Thailand; type C2 with Japan, Korea and China; type C3 with New Caledonia and Polynesia; C4 with Australia; and C5 with the Philippines. A further subtype has been described in Papua, Indonesia.^[28]

Type D has been divided into 7 subtypes (D1 — D7).

Type F has been subdivided into 4 subtypes (F1 — F4). F1 has been further divided into 1a and 1b. In Venezuela subtypes F1, F2, and F3 are found in East and West Amerindians. Among South Amerindians only F3 was found. Subtypes Ia, III, and IV exhibit a restricted geographic distribution (Central America, the North and the South of South America respectively) while clades Ib and II are found in all the Americas except in the Northern South America and North America respectively.

Life cycle[edit]

Hepatitis B virus replication .

The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process.

Attachment: The virus gains entry into the cell by binding to a receptor on the surface of the cell and enters it by endocytosis. The cell surface receptor has been identified as the NTCP sodium/bile acid transporter.
Penetration: The virus membrane then fuses with the host cell's membrane releasing the DNA and core proteins into the cytoplasm.
Uncoating: Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The core proteins dissociate from the partially double stranded viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs.
Replication: The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase.
Assembly: These four viral transcripts undergo additional processing and go on to form progeny virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies.^[19]^[29]
Release: The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.

References[edit]

^ Hunt, Richard (2007-11-21). "Hepatitis viruses". University of Southern California, Department of Pathology and Microbiology. Retrieved 2008-03-13.
^ ^a ^b Hassan MM, Li D, El-Deeb AS, et al. (October 2008). "Association between hepatitis B virus and pancreatic cancer". J. Clin. Oncol. 26 (28): 4557–62. doi:10.1200/JCO.2008.17.3526. PMC 2562875. PMID 18824707. Cite uses deprecated parameters (help)
^ Schwalbe M, Ohlenschläger O, Marchanka A, et al. (March 2008). "Solution structure of stem-loop alpha of the hepatitis B virus post-transcriptional regulatory element". Nucleic Acids Res. 36 (5): 1681–9. doi:10.1093/nar/gkn006. PMC 2275152. PMID 18263618. Cite uses deprecated parameters (help)
^ Mason, W.S., et al. (2008-07-08). "00.030. Hepadnaviridae". ICTVdB Index of Viruses. International Committee on Taxonomy of Viruses. Retrieved 2009-03-13.
^ ^a ^b Kramvis A, Kew M, François G (2005). "Hepatitis B virus genotypes". Vaccine 23 (19): 2409–23. doi:10.1016/j.vaccine.2004.10.045. PMID 15752827.
^ Magnius LO, Norder H (1995). "Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene". Intervirology 38 (1–2): 24–34. PMID 8666521.
^ Drexler JF, Geipel A, König A, Corman VM, van Riel D, Leijten LM, Bremer CM, Rasche A, Cottontail VM, Maganga GD, Schlegel M, Müller MA, Adam A, Klose SM, Borges Carneiro AJ, Stöcker A, Franke CR, Gloza-Rausch F, Geyer J, Annan A, Adu-Sarkodie Y, Oppong S, Binger T, Vallo P, Tschapka M, Ulrich RG, Gerlich WH, Leroy E, Kuiken T, Glebe D, Drosten C (2013) Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes. Proc Natl Acad Sci USA
^ Zuckerman AJ (1996). Hepatitis Viruses. In: Baron's Medical Microbiology (Baron S et al., eds.) (4th ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1.
^ Locarnini S (2004). "Molecular virology of hepatitis B virus". Semin. Liver Dis. 24 (Suppl 1): 3–10. doi:10.1055/s-2004-828672. PMID 15192795.
^ Howard CR (1986). "The biology of hepadnaviruses". J. Gen. Virol. 67 (7): 1215–35. doi:10.1099/0022-1317-67-7-1215. PMID 3014045.
^ Guo GH, Tan DM, Zhu PA, Liu F (February 2009). "Hepatitis B virus X protein promotes proliferation and upregulates TGF-beta1 and CTGF in human hepatic stellate cell line, LX-2". Hbpd Int 8 (1): 59–64. PMID 19208517. Cite uses deprecated parameters (help)
^ Benhenda S; Ducroux A, Rivière L, Sobhian B, Ward MD, Dion S, Hantz O, Protzer U, Michel ML, Benkirane M, Semmes OJ, Buendia MA, Neuveut C (2013). "Methyltransferase PRMT1 Is a Binding Partner of HBx and a Negative Regulator of Hepatitis B Virus Transcription". Journal of Virology (American Society for Microbiology) 87 (8): 4360–4371. doi:10.1128/JVI.02574-12. PMID 23388725. Cite uses deprecated parameters (help)
^ Chai N, Chang HE, Nicolas E, Han Z, Jarnik M, Taylor J (August 2008). "Properties of subviral particles of hepatitis B virus". J. Virol. 82 (16): 7812–7. doi:10.1128/JVI.00561-08. PMC 2519590. PMID 18524834. Cite uses deprecated parameters (help)
^ ^a ^b van Hemert FJ, van de Klundert MA, Lukashov VV, Kootstra NA, Berkhout B, Zaaijer HL (2011). "Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase". PLoS ONE 6 (8): e23392. doi:10.1371/journal.pone.0023392. PMC 3153941. PMID 21850270.
^ Lin B, Anderson DA (2000). "A vestigial X open reading frame in duck hepatitis B virus". Intervirology 43 (3): 185–90. PMID 11044813.
^ Osiowy C, Giles E, Tanaka Y, Mizokami M, Minuk GY (November 2006). "Molecular evolution of hepatitis B virus over 25 years". J. Virol. 80 (21): 10307–14. doi:10.1128/JVI.00996-06. PMC 1641782. PMID 17041211. Cite uses deprecated parameters (help)
^ Zhou Y, Holmes EC (2007). "Bayesian estimates of the evolutionary rate and age of hepatitis B virus". J Mol Evol 65 (2): 197–205.
^ Kay A, Zoulim F (2007). "Hepatitis B virus genetic variability and evolution". Virus Res. 127 (2): 164–76. doi:10.1016/j.virusres.2007.02.021. PMID 17383765.
^ ^a ^b Beck J, Nassal M (2007). "Hepatitis B virus replication". World J. Gastroenterol. 13 (1): 48–64. PMID 17206754.
^ Bouchard MJ, Schneider RJ (2004). "The enigmatic X gene of hepatitis B virus". J. Virol. 78 (23): 12725–34. doi:10.1128/JVI.78.23.12725-12734.2004. PMC 524990. PMID 15542625.
^ Smith Gj, 3rd; Donello, JE; Lück, R; Steger, G; Hope, TJ (1998). "The hepatitis B virus post-transcriptional regulatory element contains two conserved RNA stem-loops which are required for function". Nucleic Acids Research 26 (21): 4818–27. doi:10.1093/nar/26.21.4818. PMC 147918. PMID 9776740.
^ Flodell S, Schleucher J, Cromsigt J, Ippel H, Kidd-Ljunggren K, Wijmenga S (November 2002). "The apical stem-loop of the hepatitis B virus encapsidation signal folds into a stable tri-loop with two underlying pyrimidine bulges". Nucleic Acids Res. 30 (21): 4803–11. doi:10.1093/nar/gkf603. PMC 135823. PMID 12409471. Cite uses deprecated parameters (help)
^ Olinger CM, Jutavijittum P, Hübschen JM, et al. (November 2008). "Possible new hepatitis B virus genotype, southeast Asia". Emerging Infect. Dis. 14 (11): 1777–80. doi:10.3201/eid1411.080437. PMC 2630741. PMID 18976569. Cite uses deprecated parameters (help)
^ Kurbanov F, Tanaka Y, Kramvis A, Simmonds P, Mizokami M (August 2008). "When should "I" consider a new hepatitis B virus genotype?". J. Virol. 82 (16): 8241–2. doi:10.1128/JVI.00793-08. PMC 2519592. PMID 18663008. Cite uses deprecated parameters (help)
^ Palumbo E (2007). "Hepatitis B genotypes and response to antiviral therapy: a review". Am J Ther 14 (3): 306–9. doi:10.1097/01.pap.0000249927.67907.eb. PMID 17515708.
^ Mahtab MA, Rahman S, Khan M, Karim F (October 2008). "Hepatitis B virus genotypes: an overview". Hbpd Int 7 (5): 457–64. PMID 18842489. Cite uses deprecated parameters (help)
^ Cavinta L, Sun J, May A, et al. (June 2009). "A new isolate of hepatitis B virus from the Philippines possibly representing a new subgenotype C6". J. Med. Virol. 81 (6): 983–7. doi:10.1002/jmv.21475. PMID 19382274. Cite uses deprecated parameters (help)
^ Lusida M.I., Nugrahaputra V.E., Soetjipto Handajani R., Nagano-Fujii M., Sasayama M., Utsumi T., Hotta H. (2008). "Novel subgenotypes of hepatitis B virus genotypes C and D in Papua, Indonesia". J. Clin. Microbiol 46 (7): 2160–2166. doi:10.1128/JCM.01681-07. PMC 2446895. PMID 18463220.
^ Bruss V (2007). "Hepatitis B virus morphogenesis". World J. Gastroenterol. 13 (1): 65–73. PMID 17206755.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. B型肝炎ウイルス感染の血清学的診断 serologic diagnosis of hepatitis b virus infection
2. B型肝炎のマネージメントの概要および症例 overview of the management of hepatitis b and case examples
3. 小児におけるB型肝炎ウイルス感染の概要 overview of hepatitis b virus infection in children
4. B型肝炎ウイルス感染の臨床症状および自然経過 clinical manifestations and natural history of hepatitis b virus infection
5. B型肝炎と妊娠 hepatitis b and pregnancy

English Journal

Etiological and molecular profile of hepatocellular cancer from India.

Asim M, Sarma MP, Kar P.SourceDepartment of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India.
International journal of cancer. Journal international du cancer.Int J Cancer.2013 Jul 15;133(2):437-45. doi: 10.1002/ijc.27993. Epub 2013 Feb 13.
Hepatocellular carcinoma (HCC) cases are underreported in India. Our study was designed to investigate the etiological profile of HCC cases in India and compare with global incidence. The study included 348 HCC and 375 chronic liver disease cases without HCC as controls. Samples were screened for he
PMID 23233429

Potent killing of HBV-related hepatocellular carcinoma by a chimeric protein of anti-HBsAg single-chain antibody and truncated Bid.

Yan B, Ouyang Q, Zhao Z, Cao F, Wang T, Jia X, Meng Y, Jiang S, Liu J, Chen R, Jia L, Zhang R, Wen W, Jin B, Chen S, Zhao J, Yang A.SourceThe State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Biomaterials.Biomaterials.2013 Jul;34(20):4880-9. doi: 10.1016/j.biomaterials.2013.03.046. Epub 2013 Apr 2.
Targeted therapy is needed for hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC) which shows overexpression of HBV surface antigen (HBsAg). We previously developed scFv15, a human single-chain antibody against HBsAg. Here we tested the strategic feasibility of scFv15-mediated delivery
PMID 23562050

Hepatitis B virus status and the risk of pancreatic cancer: a meta-analysis.

Wang Y, Yang S, Song F, Cao S, Yin X, Xie J, Tu X, Xu J, Xu X, Dong X, Lu Z.SourceaDepartment of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan bDepartment of Public Management, The Humanities School, Henan University of Traditional Chinese Medicine, Zhengzhou, People's Republic of China cDepartment of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong dNorwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich, UK.
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP).Eur J Cancer Prev.2013 Jul;22(4):328-334.
OBJECTIVE: Whether hepatitis B virus (HBV) infection increases the risk of pancreatic cancer (PaC) is controversial. We carried out a meta-analysis to evaluate the association between HBV status and the risk of PaC.METHODS: PubMed, Embase, and the China National Knowledge Infrastructure were searche
PMID 23165286

Japanese Journal

Hepatitis C Virus NS3 Protein Can Activate the Notch-Signaling Pathway through Binding to a Transcription Factor, SRCAP

Iwai Atsushi,Takegami Tsutomu,Shiozaki Takuya,Miyazaki Tadaaki
PLoS One 6(6), e20718, 2011-06-06
… Persistent infections of hepatitis C virus (HCV) are known to be a major risk factor for causing hepatocellular carcinomas. …
NAID 120003075341

Molecular mechanisms of hepatocarcinogenesis in chronic hepatitis C virus infection

Yamashita Taro,Honda Masao,Kaneko Shuichi
Journal of Gastroenterology and Hepatology 26(6), 960-964, 2011-06
… Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) and chronic liver disease worldwide. …
NAID 120003141912

Related Pictures

★リンクテーブル★

リンク元	「B型肝炎ウイルス」「ワクチン」「周産期感染症」「ウイルス封入体」「Dane particle」
拡張検索	「duck hepatitis B virus」「hepatitis B virus-associated nephropathy」「hepatitis B virus X protein」「hepatitis B virus infection」
関連記事	「B」「virus」

「B型肝炎ウイルス」

Hepatitis B virus
	TEM micrograph showing hepatitis B viruses
Virus classification
Group:	Group VII (dsDNA-RT)
Order:	Unassigned
Family:	Hepadnaviridae
Genus:	Orthohepadnavirus
Species:	Hepatitis B virus

　　[★]

英: hepatitis B virus, HBV, hepatitis virus B
関: ウイルス、肝炎、B型肝炎、肝炎ウイルス

ウイルス学

二本鎖DNA。エンベロープあり。逆転写酵素を有する
ウイルス粒子：42nm
ヌクレオキャプシド：27nm

抗原＆および抗体

HBs抗原	HBsAg	表面抗原である。HBs抗原(+)はウイルスが体内に存在することを示す。
抗HBs抗体	anti-HBs	中和抗体である。抗HBs抗体(+)は過去にHBVに感染して治癒しているか、HBVワクチンを接種されているかをしめす。
HBc抗原	HBcAg	HBVを構成するタンパク質であるが、キャプシド内のタンパク質である。
抗HBc抗体-IgM	IgM anti-HBc	感染初期に現れ、数ヶ月後に消える。急性肝炎の診断に使用される。
抗HBc抗体-IgG	IgG anti-HBc	抗HBc抗体-IgMに少し遅れて現れ、ほぼ生涯にわたって血中に存在する。過去にHBVにかかったことを示す。
HBe抗原	HBe	HBe抗原は発症に遅れて一ヶ月後から増加し始め、治癒した後2,3ヶ月かけて減少する。HBe抗原(+)：HBVが増殖する際に過剰に作られるタンパク質。HBVの活発な増殖を示しており、感染力が強いことを示す。
抗HBe抗体	anti HBe	抗HBe抗体(+)：HBVウイルス量と増殖が落ち着いていることを示しており、感染力が弱いことを示す。

HBcAg

HIM.1935

ヌクレオキャプシドはC geneがコードしている。ヌクレオキャプシド：に発現している抗原をHBcAgという。

HBeAg

HIM.1935

C geneがコード。スタートコドンが箇所有り、precore regionから開始するものは小胞体シグナルを含み、細胞外に分泌される。core regionから翻訳されたものがnucleocapsid particleの組み立てに用いられる。この蛋白はRNAと結合する。ウイルスの増殖性・感染性と関係がある。HBs-Ag陽性キャリアの母親が妊娠・出産して子供にHBVが伝播する確率は、HBeAg陽性で90%、HBe陰性で10-15%。3ヶ月を越えてHBeAg陽性だったら、慢性化した事の証。(HIM.1933)
HBeAgは、HBsAgと同時かあるいはそのちょっと後に出現する。急性のB型肝炎の場合は、ALTがピークをつけたあたりで検出できなくなる。

初感染時に、末梢血でみられる血清学的変化の順番

IgM anti-HBc (対応抗原が末梢血に出てこないから検出が容易という訳じゃよ、たぶん)　－＞　anti-HBe　－＞anti-HBs

HBV抗原の局在

QB.278

HBsAg：肝細胞質内
HBeAg：肝細胞質内
HBcAg：肝細胞核内？　←　ホントかな。末梢血に出ないというだけじゃね？

抗原/抗体の状態

	HBs抗原	抗HBs抗体	抗HBc抗体	HBe抗原	抗HBe抗体	RT-PCR
未感染者	-	-	-	-	-	-
ワクチン接種者	-	+	-	-	-	-
既感染者	-	+	+	-	+	-
キャリア	+	-	+++	+	-	+
キャリア	+	-	+++	-	+	+

慢性化

HBsAgが6ヶ月以上陽性で、IgG anti-HBcが優性となり、anti-HBsは検出できないか検出限界以下となる。このころにHBV DNAは末梢血・肝細胞の核内に存在し、free or episomal form(エピソーム)として存在する。

1. replacative stage: HBVの増殖や肝障害が激しい。このstageにおいてHBV DNAは量的, HBeAgは質的なマーカーとなる。
2. nonreplacative stage: 年に～10%の割合で起こる。HBeAg陽性からanti-HBeへの血清変換(seroconversion)が起こる。この時期にたいていALTが上昇するが、身体の細胞性免疫がウイルスを排除したと考えられている。このころにはHBV DNAは核内に存在して、宿主のゲノム内にintegrateされている。末梢血にはウイルス粒子ではなく、球状・管状のウイルス粒子がみられる。肝臓の障害もやんでいる傾向にある。時に、HBeAgへの血清変換とHBV DNAの上昇、IgM anti-HBcの出現を伴ってウイルスの再活性化が起こる。IgM anti-HBcはウイルスの再活性化でも起こるから、初感染の指標としては使えないね。患者の病歴が重要。(HIM.1935)

血清変換は細胞性免疫が減弱した老人で起こりにくく、若者に多い。

3. inactive HBV carrier: nonreplicative stageに入った患者のうち、活動性の肝障害がないヒトを指している。

ウイルスの生活環

when packaging within viral peoteins is complete, synthesis of the incomplete plus strand stops

侵入＆増殖

ウイルスDNAは核内に移行
ニックの入った鎖がDNAポリメラーゼに修復され2本鎖環状DNAとなる

遺伝子型

遺伝子型	A	C
地域	海外？	日本
慢性化	する	しにくい
重症度	軽い	重い
IFN効果	奏効しやすい	奏効しにくい
腫瘍		肝細胞癌発症しやすい

潜伏期

60-160日
約35日でHBV DNAが検出可能
約59日でHBs抗原が検出可能

感染経路

水平感染：医原性(汚染した血液製剤の投与や輸血)

血液、体液、分泌液(唾液)が粘膜と接触することで引き起こされる

垂直感染：母子感染(経産道感染。経胎盤感染しない。母乳感染なし。)　⇔　ときに経胎盤感染するらしい(G10M.168)

G10M.168

		胎内感染		分娩時感染		母乳時感染
		経胎盤感染	上行性感染	経胎盤感染	産道感染	母乳感染
ウイルス	B型肝炎ウイルス	△	×	△	○	×

疫学

世界中に存在する
流行地：中国、東南アジア、サハラ砂漠地域、アマゾン川流域、太平洋湾岸地域

症状

B型肝炎

急性肝炎

発熱
黄疸

慢性肝炎

慢性化：約10% ←疫学的な値と思う

合併症

経過

感染後、10%がキャリアーとなり慢性化する

急性B型肝炎 (SMB.547)

急性B型肝炎→慢性B型肝炎
免疫能が正常な人に感染した場合、長い潜伏期の後にA型肝炎様の症状を発症する。2-4ヶ月で治癒する
1-2%の確率で劇症肝炎を引き起こす

慢性B型肝炎 (SMB.547)

HBVキャリアでかつ無症候性キャリア→慢性B型肝炎－(20-50年)→肝硬変→肝細胞癌
免疫能が十分できない新生児や小児、あるいは免疫不全患者に感染した場合は持続感染を引き起こす。

HBVキャリア：血中のHBs抗原が6ヶ月以上にわたり陽性である
無症候性キャリア：自発症状がない

キャリアとなるとウイルス量は多いが肝障害がない無症候性キャリアとなる　←　免疫系が誘導されていない。免疫寛容の状態
10-30歳で肝炎を発症し、多くの場合、B型肝炎ウイルスを排除する方向に向かっていく(HBe抗体が立ち上がる)が、10%の症例で肝炎が持続する。HBe抗体が立ち上がっても5-10%の症例で変異型HBVにより肝炎が持続する。肝炎が持続すると肝硬変、原発性肝癌を生じる (SMB.547)

検査

B型肝炎ウイルス表面抗原(HBs Ag)

治療

治療薬

急性肝炎

補助的療法

慢性肝炎

ラミブジン, インターフェロン

インターフェロン

目的：ウイルス増殖抑制による肝炎の沈静化
対象

seroconversion(HBe抗原→HBe抗体)しにくいHBe抗原陽性活動性肝炎
HBV DNA陽性・HBe抗体陽性活動性肝炎

ラミブジン

目的：救命
絶対適応：重症化、重症化の予想される慢性肝炎、活動性肝硬変、F3/A3の慢性肝炎、発症早期の劇症肝炎
相対適応：35歳以上のF2/A2慢性肝炎
禁忌　　：35歳以下でF1/A1慢性肝炎

炎症：A1<A2<A3、線維化の程度F1<F2<F3<F4

ラミブジン耐性株

エンテカビル(グアノシン類似体, DNA合成阻害)
アデフォビル

リバビリン(プリンヌクレオシド類似体)効果不明

検査

予防

HBワクチン

HBs抗原の遺伝子を酵母に遺伝子導入して作らせた成分ワクチン

HBIG(抗HBsヒト免疫グロブリン)

母子感染の予防

1. 妊婦：HBs抗原検査を行う

↓陽性

2. 妊婦：HBe抗原検査を行う

2-a.(HBe陽性)ウイルス量が多い場合の予後　：感染率100%, キャリア化率80-90%

0ヶ月：HBIG

1ヶ月：　→HBs抗原検査

2ヶ月：HBIG：B型肝炎ワクチン

3ヶ月：B型肝炎ワクチン

4ヶ月：

5ヶ月：B型肝炎ワクチン

6ヶ月：　→HBs抗原/HBs抗体検査

2-b.(HBe陰性)ウイルス量が少ない場合の予後：感染率 10%, キャリア化率まれ

0ヶ月：HBIG

1ヶ月：

2ヶ月：B型肝炎ワクチン

3ヶ月：B型肝炎ワクチン

4ヶ月：

5ヶ月：B型肝炎ワクチン

6ヶ月：　→HBs抗原/HBs抗体検査

消毒薬

アルコールでは不十分
0.5%次亜塩素酸、2%グルタルアルデヒドを用いる

ステロイド使用

http://www.kenei-pharm.com/medical/academic-info/icnews/2015/4072/

http://www.ryumachi-jp.com/info/news110926_gl.pdf#search=%27%E3%82%B9%E3%83%86%E3%83%AD%E3%82%A4%E3%83%89+B%E5%9E%8B%E8%82%9D%E7%82%8E+%E9%99%A4%E5%A4%96%27

参考

http://www.bml.co.jp/genome/product_service/invader01.html

「ワクチン」

　　[★]

英: vaccine
関: 予防接種 immunization、感染症、感染症予防法、シードロット・システム。immunization

種類

遺伝子組換えワクチン

副反応

風疹ワクチン

発熱、発疹、関節痛、リンパ節腫脹

おたふくかぜワクチン

２－３週間後、まれに、発熱、耳下腺腫脹、咳、鼻水
MMRの際に無菌性髄膜炎が数千人に一人
髄膜炎の症状：発熱、頭痛、嘔吐

学校伝染病、予防接種、ワクチン (学校伝染病、予防接種、ワクチン.xls)

病原体		感染症	ワクチン	学校伝染病	ワクチンの形状	潜伏期間	季節性	年齢	出席停止解除条件
ジフテリア菌	Corynebacterium diphtheriae	ジフテリア	ジフテリア,破傷風,百目咳混合ワクチン		トキソイド
百日咳菌	Bordetella pertussis	百日咳	ジフテリア,破傷風,百目咳混合ワクチン	○	不活化	6～14			咳の消失
結核菌	Mycobacterium tuberculosis	結核	BCG	○	不活化				伝染のおそれが無くなるまで
ポリオウイルス	poliovirus	ポリオ	ポリオワクチン(経口)		生
麻疹ウイルス	measles virus	麻疹	麻疹・風疹混合ワクチン	○	生	10～12		0～2	解熱後3日
風疹ウイルス	rubella virus	風疹	麻疹・風疹混合ワクチン	○	生	18	春～初夏	4～9	発疹消失
日本脳炎ウイルス	Japanese encephalitis virus	日本脳炎	日本脳炎ワクチン		不活化
インフルエンザウイルス	influenza virus	インフルエンザ	インフルエンザワクチン	○	不活化	1～5	冬期		解熱後2日
インフルエンザ菌	Haemophilus influenzae	化膿性髄膜炎など	Hibワクチン
肺炎球菌	Streptococcus pneumoniae
水痘・帯状疱疹ウイルス	varicella zoster virus	水痘		○	生	11～21	冬(12, 1)	5～9	発疹の痂皮化
ムンプスウイルス	mumps virus	流行性耳下腺炎		○	生	18～21			耳下腺腫脹消失
B型肝炎ウイルス	hepatitis B virus	B型肝炎			成分	60～160
A型肝炎ウイルス	hepatitis A virus	A型肝炎			不活化	15～40
狂犬病ウイルス	rabies virus	狂犬病			不活化
アデノウイルス	adenovirus	咽頭結膜熱		○
黄熱病ウイルス	yellow fever virus	黄熱病			生