Hepatitis E pathophysiology
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Consensus has not been reached regarding the complete pathogenesis of HEV. Evidence shows that the virus exposes its RNA within the host cell's cytoplasm, where it is translated into a negative RNA strand that contains ORFs 1, 2 and 3 that are involved in the replication of the virus. HEV is not cytopathic, and the manifestations of the disease result from the body's immune response towards the infected cells. The transmission of the disease depends on the genotype of the virus. It may be transmitted through ingestion of contaminated water, in genotypes 1 and 2, or ingestion of uncooked meat, genotypes 3 and 4. Acute hepatitis E has been noted to progress to chronic disease in HIV infected patients with a low CD4 count. Solid organ transplanted patients are commonly asymptomatic, or have mild symptoms of the disease. 60% of infected patients with an organ transplant, develop chronic hepatitis E, and 10% develop liver cirrhosis. Infection is usually due to HEV genotype 3, and diagnostic studies should be based on the identification of HEV RNA by PCR technique. Histological changes of the liver of patients with chronic disease include: portal hepatitis; lymphocytic infiltrates; necrosis; and fibrosis.
The cellular receptor for HEV and the mode of entry of the virus into the host cell are yet to be identified. 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 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.
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.
Hepatitis E is mainly transmitted through the fecal-oral route. In developing countries it occurs mostly from the ingestion of contaminated water. Although person to person transmission is uncommon, a recent case in Uganda has suggested possible transmission among persons living in the same house.
- Transmission through blood transfusions
- Transmission through organ transplants
- Vertical transmission from an infected mother to the fetus
There is a low incidence of persistent infection with HEV in HIV patients. However, acute HEV infection in these patients, particularly in those with low levels of CD4, is associated with progression to chronic disease.
Organ Transplant Recipients
Chronic hepatitis E is associated with organ transplants, including liver, kidney and heart. Cases have been reported in which liver transplants carrying HEV, lead to rapid liver cirrhosis. Patients who have received a solid organ transplant, with elevated levels of liver enzymes, in the absence of other causes of hepatitis, should be evaluated for HEV RNA.
|Clinical Manifestations||Mild symptoms or asymptomatic|
Jaundice is present in few patients
|ALT Levels at Diagnosis||Mild ALT elevation (≈300 IU/L)|
|Viral Genotype||Genotype 3|
|Outcomes||60% infected patients develop chronic hepatitis E|
10% infected patients develop liver cirrhosis
- Level of immunosuppression
- Period between infection and latest episode of acute rejection
- Time since organ transplant
- Low leukocytes levels
- Low lymphocyte count
- Low levels of T-cells
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