Hepatitis D pathophysiology: Difference between revisions
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===Transmission=== | ===Transmission=== | ||
HDV is transmitted [[percutaneously]] or sexually through contact with infected blood or blood products. [[Perinatal]] transmission is possible but uncommon. Blood is potentially infectious during all phases of active hepatitis D infection and a very small [[inoculum]] is sufficient to transmit HDV infection. Peak [[infectivity]] probably occurs just before the onset of acute disease. <ref name="GAR">World Health Organization. Global Alert Response. Hepatitis D 2001. http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/</ref> | HDV is transmitted [[percutaneously]] or sexually through contact with infected blood or blood products. [[Perinatal]] transmission is possible but uncommon. Blood is potentially infectious during all phases of active hepatitis D infection and a very small [[inoculum]] is sufficient to transmit HDV infection. Peak [[infectivity]] probably occurs just before the onset of acute disease. <ref name="GAR">World Health Organization. Global Alert Response. Hepatitis D 2001. http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/</ref> | ||
==Macroscopic Pathology== | ==Macroscopic Pathology== | ||
Revision as of 19:35, 5 August 2014
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Hepatitis D |
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Hepatitis D pathophysiology On the Web |
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American Roentgen Ray Society Images of Hepatitis D pathophysiology |
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Risk calculators and risk factors for Hepatitis D pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Jolanta Marszalek, M.D. [2] João André Alves Silva, M.D. [3]
Overview
There is limited knowledge concerning the pathogenesis of hepatitis delta virus (HDV) infection. The mechanisms determining whether a person will spontaneously clear HDV, become chronically infected, or rapidly progress to hepatic fibrosis are not yet fully understood.[1]Pathological changes in HDV are limited to the liver, the only organ in which HDV can replicate. Hepatits B virus(HBV) is an essential co-factor in the evolution of hepatocellular damage, and infection with both HBV and HDV leads to more severe liver injury than HBV infection alone. There is evidence supporting the possibility that the virus can be cytopathic in certain genotypes.
Pathogenesis
Studies demonstrate that both the adaptive and innate immune systems may play an important role in liver injury and clearance of the virus, although these immune responses are poorly defined. Evidence points to an association between the quantity and quality of host T-cell responses and the level of infection control.[2] HDV appears to subvert the adaptive immune system away from Th-1 biased CD4 and CD8 T-cell response, a necessary process for viral clearance.
Hepatits B virus(HBV) is an essential co-factor in the evolution of hepatocellular damage, and infection with both HBV and HDV leads to more severe liver injury than HBV infection alone. The fluctuating viral load of both HDV and HBV in different stages of infection may signify a direct association with the pathogenesis of disease progression. Studies have shown that during the acute phase of HDV infection, HDV viremia is associated with an increased level of alanine transaminase (ALT) and suppressed HBV. In the later stages of the chronic phase, HDV RNA decreases, HBV reactivates, and levels of transaminases are moderately elevated. At this point, either HDV or HBV replicate and lead to cirrhosis and hepatocellular carcinoma(HCC) or both viruses are cleared and there is remission. [1]
HDV suppresses HBV replication among patients with either co-infection or superinfection. In fact, up to 90% of patients with HDV co-infection are HBeAg negative and have a low HBV viral load. Furthermore, once HDV infection is cleared, replication of HBV can reactivate.[1] Evidence points to the possible role of the small(p24) and large(p27) HDV proteins in suppressing HBV replication by:[3]
- repressing the activity of two enhancer regions (pIIE1 and pIIE2)in the HBV genome
- transactivation of the MxA gene leading to the reduction of viral HBV mRNA export from the nucleus
Although hepatitis D is thought to be a largely immune-mediated disease process, there is evidence demonstrating that HDV may be cytopathic. Specifically, outbreaks of fulminant hepatitis induced by HDV genotype 3 link uncommon histological features to the potentially cytopathic nature of HDV.[4] More data is necessary to further the understanding of underlying mechanisms of HDV-induced disease.[1]
Transmission
HDV is transmitted percutaneously or sexually through contact with infected blood or blood products. Perinatal transmission is possible but uncommon. Blood is potentially infectious during all phases of active hepatitis D infection and a very small inoculum is sufficient to transmit HDV infection. Peak infectivity probably occurs just before the onset of acute disease. [5]
Macroscopic Pathology
Microscopic Pathology
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References
- ↑ 1.0 1.1 1.2 1.3 Hughes SA, Wedemeyer H, Harrison PM (2011). "Hepatitis delta virus". Lancet. 378 (9785): 73–85. doi:10.1016/S0140-6736(10)61931-9. PMID 21511329.
- ↑ Nisini R, Paroli M, Accapezzato D, Bonino F, Rosina F, Santantonio T; et al. (1997). "Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles". J Virol. 71 (3): 2241–51. PMC 191332. PMID 9032359.
- ↑ Williams V, Brichler S, Radjef N, Lebon P, Goffard A, Hober D; et al. (2009). "Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene". J Gen Virol. 90 (Pt 11): 2759–67. doi:10.1099/vir.0.011239-0. PMID 19625466.
- ↑ Wedemeyer H, Manns MP (2010). "Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead". Nat Rev Gastroenterol Hepatol. 7 (1): 31–40. doi:10.1038/nrgastro.2009.205. PMID 20051970.
- ↑ World Health Organization. Global Alert Response. Hepatitis D 2001. http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/