Hepatitis E pathophysiology
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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 associated with hepatocyte injury from endotoxins, and an increased Th2 response.[4]
Transmission
Hepatitis E is mainly transmitted through the fecal-oral route. In developing countries it occurs mostly from the ingestion of contaminated water.[5] Although person to person transmission is uncommon, a recent case in Uganda has suggested possible transmission among persons living in the same house.[6]
Some genotypes are more associated with a specific route of transmission:[5]
- Genotypes 1 and 2 - waterborne transmission
- Genotypes 3 and 4 - ingestion of uncooked meat
Other noted routes of transmission include:[5][7]
- Transmission through blood transfusions
- Transmission through organ transplants
- Vertical transmission from an infected mother to the fetus
Associated Conditions
HIV Co-Infection
Organ Transplant Recipients
Chronic hepatitis E is associated with organ transplants, such as liver, kidney and heart.[8][9][10] There have been reported cases in which liver transplant carrying HEV, lead to rapid cirrhosis.[11]
Chronic hepatitis E in organ-transplanted patients commonly has the following features:
| Parameter | Features |
|---|---|
| ALT Levels at Diagnosis | |
| Viral Genotype | |
| Diagnostic Techniques | |
| Outcomes | |
| Therapy |
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][10]
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.
- ↑ 5.0 5.1 5.2 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
- ↑ Howard CM, Handzel T, Hill VR, Grytdal SP, Blanton C, Kamili S; et al. (2010). "Novel risk factors associated with hepatitis E virus infection in a large outbreak in northern Uganda: results from a case-control study and environmental analysis". Am J Trop Med Hyg. 83 (5): 1170–3. doi:10.4269/ajtmh.2010.10-0384. PMC 2963989. PMID 21036857.
- ↑ Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
- ↑ Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N; et al. (2010). "Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients". Liver Transpl. 16 (1): 74–82. doi:10.1002/lt.21958. PMID 19866448.
- ↑ Kamar N, Selves J, Mansuy JM, Ouezzani L, Péron JM, Guitard J; et al. (2008). "Hepatitis E virus and chronic hepatitis in organ-transplant recipients". N Engl J Med. 358 (8): 811–7. doi:10.1056/NEJMoa0706992. PMID 18287603.
- ↑ 10.0 10.1 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.
- ↑ Schlosser B, Stein A, Neuhaus R, Pahl S, Ramez B, Krüger DH; et al. (2012). "Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient". J Hepatol. 56 (2): 500–2. doi:10.1016/j.jhep.2011.06.021. PMID 21798217.