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Other Infections

Hepatitis E Uncommon among HIV+ People, but May Cause Unexplained Liver Enzyme Elevations

Coinfection with hepatitis E virus (HEV) is not commonly seen in people with HIV, according to 2 recent reports, but it is a possibility to consider if a person has elevated liver enzymes not attributable to another apparent cause.alt

Hepatitis E typically causes acute liver disease, but can sometimes cause chronic diseases that can progress to cirrhosis, especially in people with compromised immune systems. Like hepatitis A, it is primarily spread through contaminated food or water -- not via blood like hepatitis B and C -- and outbreaks most often occur in resource-limited settings with poor sanitation.

UK Study

As described in the January 2012 issue of HIV Medicine, F. Keane from Royal Cornwall Hospital and colleagues sought to document the incidence of chronic HEV coinfection among people with HIV, and to compare HEV seroprevalence (presence of anti-HEV antibodies) between HIV positive and HIV negative populations.

This case-control cohort study was carried out at 2 teaching hospitals in southwest England. A total of 138 HIV positive patients were tested for HEV IgM and IgG antibodies; in addition, 464 HIV negative control participants were tested for HEV IgG.


  • There was no difference in HEV IgG seroprevalence between the HIV positive patients and the control group.
  • The only risk factor for HEV seropositivity was consumption of raw or undercooked pork.
  • Sexual risk factors were unrelated to HEV seroprevalence.
  • No HIV positive patients showed evidence of chronic HEV coinfection.

"Anti-HEV seroprevalence is similar in controls and patients with HIV infection," the study authors concluded. "Risk factor analysis suggests that HEV is unlikely to be transmitted sexually."

"Chronic coinfection with HEV was absent, indicating that chronic HEV/HIV coinfection is not a common problem in this cohort," they added.

Swiss Study

In the second study, described in the June 2011 issue of Emerging Infectious Diseases, investigators with the Swiss HIV Cohort Study screened for HEV IgG antibodies in HIV patients with unexplained alanine aminotransferase (ALT) elevation. Above-normal ALT is a sign of liver inflammation and may suggest various problems include drug-induce liver toxicity or viral hepatitis.

This analysis included 735 HIV positive people with at least 2 consecutive elevated ALT measurements (> 60 IU/L); patients with hepatitis B or C were excluded.


  • 19 patients were seropositive for HEV, a seroprevalence rate of 2.6%.
  • Women and people of Asian descent were more likely to be HEV antibody positive, but there was no association with age or HIV risk group.
  • After adjusting for other factors, people with CD4 cell counts of 100-350 cells/mm3 were nearly 5 times more likely to be antibody HEV positive that those with higher levels (odds ratio 4.68).
  • Sequential blood tests showed that 5 patients with HEV had experienced recent seroconversion.
  • 1 person with a very low CD4 T-cell count had prolonged detectable HEV RNA (genetic material), indicating that the virus can persist past the acute stage in people with compromised immunity.

Based on these findings, the researchers recommended that, "chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation."

Describing the single individual with persistent detectable HEV RNA, they noted that he started antiretroviral therapy (ART) with a CD4 count of about 30 cells/mm3, and HEV antibody seroconversion was delayed until immune reconstitution occurred. Once the patient's CD4 count increased to about 80 cells/mm3 HEV RNA clearance occurred, and his ALT levels returned to normal after it rose above 100 cells/mm3.

Further testing identified a second immunocompromised patient with detectable HEV RNA but undetectable HEV antibodies; this individual -- who did not experience good immune reconstitution on ART -- had sporadic detectable HEV RNA. The authors found 2 prior cases in the literature in which people with CD4 counts below 200 cells/mm3 developed persistent HEV infection.

Since people with severe immune suppression may not produce enough antibodies, antibody screening may not be adequate to diagnose HEV infection in this group, they cautioned.

"We did not find higher HEV prevalence in subgroups previously considered at higher risk of HEV infection such as [men who have sex with men], injection drug users, and prisoners," the researchers elaborated in their discussion.

Noting that the HEV rate is lower in Switzerland than in other European countries and the U.S., they continued, "It is now well established that pigs and other animal species constitute reservoirs for HEV and that transmission in industrialized countries occurs mainly through contaminated meat. We hypothesize that strict regulation of animal imports in Switzerland may reduce HEV prevalence among farm animals."

Investigator affiliations:

Keane study: Department of Genitourinary Medicine, Royal Cornwall Hospital, Truro Department of Genitourinary Medicine, Southmead Hospital, Bristol Department of Clinical Microbiology, Royal Cornwall Hospital, Truro European Centre for Environment & Human Health, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, Truro Centre for Health and Environmental Statistics, University of Plymouth, Plymouth Virus Reference Department, Centre for Infections, Health Protection Agency, London, UK.

Kenfak-Foguena study: Centre Hospitalier Universitaire Vaudois and Lausanne University, Lausanne, Switzerland; Data Center of the Swiss HIV Cohort Study, Lausanne; Cantonal Hospital St. Gallen, St. Gallen, Switzerland; University of Zurich, Zurich, Switzerland; University Hospital Geneva, Geneva, Switzerland; Inselspital Klinik und Poliklinik für Infektiologie, Bern, Switzerland; Universitätsspital Klinik für Infektiologie, Basel, Switzerland; Ospedale Civico Servizio Malattie Infettive, Lugano, Switzerland; Klinik Im Park, Zurich; Centre Hospitalier Universitaire de Toulouse, Toulouse, France.



F Keane, M Gompels, R Bendall, et al. Hepatitis E viruscoinfection in patients with HIV infection. HIV Medicine 13(1):83-88. January 2012.

A Kenfak-Foguena, F Schöni-Affolter, P Bürgisser, et al. Hepatitis E Virus seroprevalence and chronic infections in patients with HIV, Switzerland. Emerging Infectious Diseases 17(6):1074-1078. June 2011.