Reply
Authors: Chong‐Gee Teo, Ajay Yesupriya, Man‐Huei Chang, Lyna Zhang
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. We appreciate the attention that Pischke et al. has given to our report. Pischke et al., in averring that anti–hepatitis E virus (HEV) seropositivity is based on lifestyle, seem disposed to exclude the possibility that genetic susceptibility contributes. Host genetic variation influences susceptibility to infectious diseases1: why genetic variation would not similarly influence susceptibility to HEV infection or hepatitis E would be puzzling. Pischke et al. suggest further that one‐quarter of American Muslims being non‐Hispanic blacks confounds our findings as Muslims do not consume porcine food products. The National Health and Nutrition Examination Survey does not collect data on religious affiliation. Further, in 1990 (i.e., about the time the Third National Health and Nutrition Examination Survey was conducted), only an estimated 1% of American, non‐Hispanic blacks were Muslims.2 The likelihood of confounding by such a small proportion seems remote. Moreover, Pischke et al. assume that Muslims, on account of their dietary preferences, are thereby not at risk of HEV infection. They have not considered that American Muslims may adopt the lifestyles of and share the same environment with other Americans that can expose them to HEV, such as travel to HEV‐hyperendemic countries, recreational or occupational contact with HEV‐infected animals, and ingestion of water contaminated by HEV shed fecally from infected humans and animals.3 Pischke et al. state that "Anti‐HEV seropositivity reflects a past or present immune response to HEV but is not informative on the host's response to HEV." However, the immune response is, per se, a constituent of the host's response. In bringing up the example of the interleukin‐28B gene as being able to influence clearance of HCV infection, it becomes apparent that by "host's response" they mean that which leads to clearance or persistence of infection. Our study, however, concerns identification of a host genetic factor—in this case in or linked to the apolipoprotein E (APOE) gene, which protects against susceptibility to infection (which results in seropositivity), not outcome of infection (which leads to clearance or chronicity). Pischke et al. also suggest that any study on the protective effect of a genetic variant should distinguish between asymptomatic and symptomatic infection. We reiterate that the protection we were studying concerns susceptibility to, not outcome of, infection. Pischke et al. disagree with our consideration that ApoE might protect against HEV infection from its incorporation in the HEV envelope. This possibility is but one of several possibilities we discussed to explain why ApoE might confer protection. Another, closely related, possibility we presented—that ApoE incorporated into the viral envelope can influence antibody neutralization—finds support in a recently reported study of HCV.4 Finally, the further lines of inquiry suggested by Pischke et al. are confined to symptomatic infection and to consumption of porcine food products. They do not consider that HEV infection may not be clinically overt and that (as we have alluded above) adopting lifestyles of and sharing the same environment with fellow members of the population can contribute.