The Association of Cytokines and Micronutrients with Hepatitis E Virus Infection During Pregnancy and the Postpartum Period in Rural Bangladesh

Abstract

Abstract. Hepatitis E virus (HEV) infection is severe during pregnancy, with a pregnant case fatality rate around 30%. In Bangladesh, plasma samples from 1,100 women during the first trimester (TM) and third TM of pregnancy and 3 months postpartum (PP) were tested for anti-HEV IgG. During this time, 40 women developed antibody responses to HEV. These seroconverters are classified as the cases (incidence = 46 infections per 1,000 personyears). All except one seroconversion occurred between the third TM and 3 months PP. The cases and 40 matched non-seroconverters (controls) underwent analysis of a panel of 10 cytokines, 12 vitamins and minerals, and two markers of inflammation. Throughout pregnancy, seroconverting cases displayed higher concentrations of both pro-and anti-inflammatory cytokines compared with the non-seroconverting controls, even prior to infection. In the first TM, seroconverters had lower circulating zinc concentrations (P = 0.03), an increased prevalence of vitamin D deficiency (25-hydroxy vitamin D [25(OH)2D] < 50 nmol/L, P = 0.08), and anemia (hemoglobin < 110 g/L, P = 0.05) compared with controls. There were no differences in C-reactive protein or α-1-acid glycoprotein. Antecedent micronutrient deficiencies may lead to dysregulated cytokine expression and immunologic compromise, increasing the risk of HEV infection, especially during pregnancy. This exploratory analysis reveals potential novel associations that deserve further study.

Arsenic exposure and hepatitis E virus infection during pregnancy

“…Plasma cytokine measurements have been described in detail elsewhere (Kmush et al, In press). In brief, cytokine levels of all HEV seroconverting and non-seroconverting women were determined by the electrochemiluminescence-based Meso Scale Discovery (MSD) immunoassay in the format of the Human Th1/Th2 10-Plex Ultra-Sensitive Kit for IFN-γ, IL-10, IL-12, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-8, and TNF-α according to manufacturer protocols (Meso Scale Discovery, Gaithersburg, MD).…”

Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

“…Other host factors, such as nutritional status, including micronutrient or folate deficiencies, or differences in major histocompatibility complex, may also influence the immune response of pregnant women to HEV [149]. This may be why HEV infections are benign in pregnant women in Egypt, although they are caused by HEV1 [150].…”

Hepatitis E and pregnancy: current state

“…During pregnancy, the immune system is altered to protect the fetus from attacks by the mother's immune system; however, these changes also affect the way the immune system responds to infectious agents. Several studies (Table ).have shown significant differences in the immune and hormonal responses in pregnant women with FHF caused by hepatitis E …”

“…Certain factors, such as nutritional state (micronutrient deficiencies) and the lack of folic acid, can also affect the immune response to HEV infection in pregnant women . Thus, Kmush et al in their study conclude that micronutrient deficiencies, from inadequate diet, and a high infectious disease burden may lead to immunologic compromise, including impaired mucosal immunity and dysregulated cytokine expression. This dysregulation in turn may lead to dysfunction of the immune system, increasing the risk of HEV infection (and perhaps the risk of other infections as well).…”

“…Several studies ( Table 2).have shown significant differences in the immune and hormonal responses in pregnant women with FHF caused by hepatitis E. [45][46][47][48][49][50][51][52][53][54][55][56][57] One of the main changes during pregnancy is the decrease in cellular immunity, which presents itself as a decrease of CD4, an increase of CD8, and, therefore, a decrease in the CD4/CD8 ratio. Moreover, the changes in the maternal immune response are partially due to significant variations in hormone levels, with an increase in progesterone, estrogen, and human chronic gonadotropin.…”