Hepatitis E pathophysiology: Difference between revisions
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==Pathogenesis== | ==Pathogenesis== | ||
The cellular [[receptor]] for [[HEV]] and the mode of entry of the [[HEV|virus]] into the host cell are yet to be identified.<ref name="pmid19812150">{{cite journal| author=Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S| title=Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. | journal=J Virol | year= 2009 | volume= 83 | issue= 24 | pages= 12714-24 | pmid=19812150 | doi=10.1128/JVI.00717-09 | pmc=PMC2786843 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19812150 }} </ref> However, heparin sulfate [[proteoglycans]] are known to be required for the attachment to target cells and [[infection]]. A proposed theory for the [[viral replication|replication]] of [[HEV|virus]] is that, once within the host cell, [[HEV]] exposes its [[RNA]], which is then [[translation|translated]] into [[proteins]] ([[ORF]]1) that will be responsible for the production of a negative-strand [[RNA]]. This newly produced strand will serve as a template for new [[genomic]] and subgeneric [[RNA]]s. The new RNAs, are translated to [[ORF]]2 and [[ORF]]3. The [[ORF]] proteins will then transport the [[RNA]] into new [[virions]] that will use cellular [[lipids]] and [[ORF]]3 for their formation.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref><ref name="pmid21068219">{{cite journal| author=Nagashima S, Takahashi M, Tanaka T, Yamada K, Nishizawa T et al.| title=A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. | journal=J Gen Virol | year= 2011 | volume= 92 | issue= Pt 2 | pages= 269-78 | pmid=21068219 | doi=10.1099/vir.0.025791-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21068219 }} </ref> | The cellular [[receptor]] for [[HEV]] and the mode of entry of the [[HEV|virus]] into the host cell are yet to be identified.<ref name="pmid19812150">{{cite journal| author=Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S| title=Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. | journal=J Virol | year= 2009 | volume= 83 | issue= 24 | pages= 12714-24 | pmid=19812150 | doi=10.1128/JVI.00717-09 | pmc=PMC2786843 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19812150 }} </ref> However, heparin sulfate [[proteoglycans]] are known to be required for the attachment to target cells and [[infection]]. A proposed theory for the [[viral replication|replication]] of [[HEV|virus]] is that, once within the host cell, [[HEV]] exposes its [[RNA]], which is then [[translation|translated]] into [[proteins]] ([[ORF]]1) that will be responsible for the production of a negative-strand [[RNA]]. This newly produced strand will serve as a template for new [[genomic]] and subgeneric [[RNA]]s. The new RNAs, are translated to [[ORF]]2 and [[ORF]]3. The [[ORF]] proteins will then transport the [[RNA]] into new [[virions]] that will use cellular [[lipids]] and [[ORF]]3 for their formation.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref><ref name="pmid21068219">{{cite journal| author=Nagashima S, Takahashi M, Tanaka T, Yamada K, Nishizawa T et al.| title=A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. | journal=J Gen Virol | year= 2011 | volume= 92 | issue= Pt 2 | pages= 269-78 | pmid=21068219 | doi=10.1099/vir.0.025791-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21068219 }} </ref> | ||
Similarly to other hepatitis viruses, HEV is not cytopathic. The host's immune response to the infection is the cause of liver injury.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref> | |||
Although the pathogenesis behind the increased mortality of infected pregnant women is not completely understood, it is thought to be related to hepatocyte injury mediated by endotoxins, and greater T-cell type 2 response.<ref name="pmid15955220">{{cite journal| author=Pal R, Aggarwal R, Naik SR, Das V, Das S, Naik S| title=Immunological alterations in pregnant women with acute hepatitis E. | journal=J Gastroenterol Hepatol | year= 2005 | volume= 20 | issue= 7 | pages= 1094-101 | pmid=15955220 | doi=10.1111/j.1440-1746.2005.03875.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15955220 }} </ref> | |||
===Transmission=== | ===Transmission=== | ||
Revision as of 11:30, 27 August 2014
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Pathogenesis
The cellular receptor for HEV and the mode of entry of the virus into the host cell are yet to be identified.[1] However, heparin sulfate proteoglycans are known to be required for the attachment to target cells and infection. A proposed theory for the replication of virus is that, once within the host cell, HEV exposes its RNA, which is then translated into proteins (ORF1) that will be responsible for the production of a negative-strand RNA. This newly produced strand will serve as a template for new genomic and subgeneric RNAs. The new RNAs, are translated to ORF2 and ORF3. The ORF proteins will then transport the RNA into new virions that will use cellular lipids and ORF3 for their formation.[2][3]
Similarly to other hepatitis viruses, HEV is not cytopathic. The host's immune response to the infection is the cause of liver injury.[2]
Although the pathogenesis behind the increased mortality of infected pregnant women is not completely understood, it is thought to be related to hepatocyte injury mediated by endotoxins, and greater T-cell type 2 response.[4]
Transmission
The hepatitis E virus is transmitted mainly through the fecal-oral route, due to fecal contamination of drinking water.
Other transmission routes have been identified, including:
- Foodborne transmission from ingestion of products derived from infected animals
- Transfusion of infected blood products
- Vertical transmission from a pregnant woman to her fetus
- Ingestion of raw or uncooked shellfish has also been identified as the source of sporadic cases in endemic areas.
Although humans are considered the natural host for the hepatitis E virus, antibodies to the hepatitis E virus or closely related viruses have been detected in primates and several other animal species, suggesting infection by the virus.
Hepatitis E is a waterborne disease. Contaminated water or food supplies have been implicated in major outbreaks.
Associated Conditions
HIV Co-Infection
Organ Transplant Recipients
Gross Pathology
Microscopic Pathology
Patients who develop chronic liver disease often have changes in liver histology. These may include:[2]
- Portal hepatitis
- Lymphocytic infiltrate
- Necrosis
- Fibrosis
In severe cases, these changes may evolve to fibrosis and cirrhosis.[2][5]
References
- ↑ Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S (2009). "Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection". J Virol. 83 (24): 12714–24. doi:10.1128/JVI.00717-09. PMC 2786843. PMID 19812150.
- ↑ 2.0 2.1 2.2 2.3 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.
- ↑ Nagashima S, Takahashi M, Tanaka T, Yamada K, Nishizawa T; et al. (2011). "A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells". J Gen Virol. 92 (Pt 2): 269–78. doi:10.1099/vir.0.025791-0. PMID 21068219.
- ↑ Pal R, Aggarwal R, Naik SR, Das V, Das S, Naik S (2005). "Immunological alterations in pregnant women with acute hepatitis E." J Gastroenterol Hepatol. 20 (7): 1094–101. doi:10.1111/j.1440-1746.2005.03875.x. PMID 15955220.
- ↑ Gérolami R, Moal V, Colson P (2008). "Chronic hepatitis E with cirrhosis in a kidney-transplant recipient". N Engl J Med. 358 (8): 859–60. doi:10.1056/NEJMc0708687. PMID 18287615.