Hepatitis E virus infection associated with HIV and damage to gut mucosa, Zambian study shows

Michael Carter
Published: 13 September 2013

The prevalence of hepatitis E virus (HEV) infection is strongly associated with HIV status, results of a study conducted in Zambia and published in the online edition of the Journal of Infectious Diseases show. There was a 71% prevalence of HEV infection among HIV-positive adults, compared to a prevalence of 24% in HIV-negative adults.

“HIV was strongly associated with HEV status in adults,” comment the authors. “We suspect that increased susceptibility is the likeliest explanation.”

There was also a strong association between HEV infection and damage to gut mucosa.

HEV is one of the leading causes of hepatitis globally and is associated with a high mortality rate in pregnant women. The main mode of HEV transmission in resource-limited setting is via faeco-oral contact, often due to use of contaminated water. Individuals in settings with a high prevalence of HEV are also at risk of acquiring a number of other gut infections via contaminated water or poor hygiene. This can cause damage to gut tissue, a condition often called environmental enteropathy.

Chronic HEV infection has been observed in people with HIV. Areas of high HIV and HEV prevalence overlap, meaning that there is a risk of co-infection. However, little is known about the prevalence of HEV infection in communities with a high burden of HIV.

An international team of investigators therefore designed a study to determine HEV prevalence among adults and children in the Misisi township, Zambia.

Two separate sample sets were used. Prevalence in adults was analysed using blood samples collected in 1999. To assess prevalence in children (aged one to 15 years), blood samples were collected in a prospective study conducted in 2011.

All samples were tested for antibodies to HEV (IgG, with positive samples also tested for IgM).

Gut tissue samples were obtained from adults via biopsy to see if HEV infection was associated with muscosal damage. Villous height, crypt depth and epithelial surface area were investigated.

A total of 106 adults and 194 children were included in the study. None of the participants had jaundice.

Prevalence of HEV antibodies in children increased with age, from 8% in those aged between one and four years to 36% in children aged ten to 14 years.

The prevalence of HEV antibodies was higher in boys than girls (20 vs 13%). This difference was not significant, but the authors note this finding is “consistent with the higher attack rate in men in most epidemics”.

The overall prevalence of HEV antibodies in adults was 42%. However, this differed significantly according to HIV infection status, and was significantly higher among HIV-positive individuals than HIV-negative individuals (71 vs 28%).

Analysis of risk factors for HEV infection in children showed that storage of drinking water in a closed container was associated with a non-significant reduction in the risk of carrying HEV antibodies. The investigators believe this finding “suggests that poor quality drinking water does increase HEV transmission in children”.

In adults, being HIV positive was strongly associated with infection with HEV (OR = 8.4; 95% CI, 3.0-23.0; p = 0.0001).

The relationship between HEV infection and damage to gut mucosa was then explored. Villous height was lower and crypt depth higher in adults positive for HEV antibodies.

There was evidence of an interaction with HIV. Villous depth was significantly lower among HIV-positive adults than HIV-negative adults (p = 0.04). Crypt depth was also significantly higher in those with HIV (p = 0.0001).

“HEV and HIV are both associated with similar changes in villous height and crypt depth, and both are associated with non-significant reductions in epithelial surface area,” write the authors.

Restricting analysis to people with HIV showed that HEV infection was associated with greater crypt depth but not villous height. “It is likely that larger studies may be required to resolve the relative ‘contributions’ of these two viruses,” suggest the investigators.


Jacobs C et al. Seroepidemiology of hepatitis E virus infection in an urban population in Zambia: strong association with HIV and environmental enteropathy. J Infect Dis, online edition, 2013.

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