Hepatitis E Virus and HIV Coinfection Research
Infection with hepatitis E virus (HEV) is uncommon but apparently emerging in the high-income regions of North America, Western Europe and Australia. However, HEV is relatively common in parts of Asia, Africa and Central America. In these regions, HEV is commonly spread to people when sewage contaminates drinking water supplies. HEV can be associated with symptom-free infection or more severe symptoms associated with viral hepatitis, such as the following:
- yellowing of the skin and whites of the eyes
- dark urine
- loss of appetite
- abdominal pain
- muscle, bone and joint pain
In high-income countries, cases of HEV have been linked to eating undercooked products made from certain animals such as these:
- pigs (including pig liver and sausages)
- wild boar
(Ken Sherman, M.D., University of Cincinnati College of Medicine, personal communication)
Another source of exposure to HEV is recent travel to a region where HEV infection is relatively common.
Most cases of HEV resolve without intervention. In rare cases treatment has been necessary and there are reports of successful recovery when the broad-spectrum antiviral agent ribavirin has been used, with or without interferon-alpha.
In most cases of HEV infection in people in high-income countries, this virus does not appear to cause chronic disease that leads to liver damage. However, in the past decade, research teams in Western Europe have been reporting clusters of HEV infection in people with weakened immune systems due to cancer and organ transplantation. In these particular cases, liver damage has occurred.
Due to these reports, other research teams have been concerned that people whose immune systems are weakened from HIV infection may also be at risk for becoming infected with HEV and developing liver damage. Here are findings from several studies by those other research teams.
A team in the southern UK at hospitals in Truro and Bristol tested blood samples from 138 HIV-positive people and 463 HIV-negative people for antibodies to HEV -- suggesting exposure to this virus. They were also tested for HEV's genetic material using PCR (polymerase chain reaction); this is suggestive of active HEV infection. The team found no differences in rates of exposure to HEV between the two populations studied. Moreover, no HIV-positive people had chronic HEV infection.
A large team of researchers in both northern and southern France -- in towns and cities such as Hyères, Maison-Alfort, Marseille, Pau, Paris and Toulon -- conducted a study with 245 HIV-positive people. Using antibody and PCR testing, technicians found that about 3% of people from northern France had been exposed to HEV in the past, compared to about 9% in southern France. No cases of chronic HEV infection were found among HIV-positive people.
Researchers in this country tested 735 HIV-positive people who had unexplained elevations in ALT for exposure to HEV. They found that about 3% of people had been exposed to this virus. None of the people in this study had infection with hepatitis B or C viruses. Only one patient had chronic HEV infection, lasting for 24 months while he had a low CD4+ count (less than 100 cells). Once he began ART and his CD4+ count rose, he recovered from HEV infection.
One study to investigate HEV infection among HIV-positive people was done by a consortium of military medical researchers in the U.S. Researchers analysed stored blood samples that had been collected between 1985 and 2009 because people had been having elevated levels of the liver enzyme ALT (alanine aminotransferease) in the blood by at least five times above the upper limit of normal. Elevations of such magnitude are suggestive of liver injury, such as that caused by viral infection of the liver. The research team scoured the medical records of 4,410 HIV-positive people and found blood samples from 194 that were available for HEV testing. In total, testing revealed that 13 people had been exposed to HEV.
There were no increases in HEV infections between 1985 and 2009. In general, there were no differences in the characteristics of people exposed to HEV and those who were not. The exception was that HEV-positive people tended to have higher HIV viral loads than HEV-negative people. None of the 13 HEV-positive people developed chronic HEV infection.
Taken together, the results from these studies suggest that HEV does not seem to be more common among HIV-positive people.
Several of the research teams mentioned above, including the American one, have proposed that a diagnosis of HEV infection be considered for people with symptoms or lab tests suggestive of "viral-like hepatitis." Antibody testing for HEV may return with a negative result despite ongoing HEV infection. Therefore, the U.S. team suggests that among HIV-positive people, particularly those with low CD4+ cell counts, PCR testing should be used to assess HEV infection status. Furthermore, they add that HIV-positive people who take ART may be better able to recover from HEV, but this needs to be proven in a study.
Further general research on HEV is being done by the U.S. Centers for Disease Control and Prevention (CDC) as well as by scientists in Western Europe.
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