A Mutation in the Progesterone Receptor Is Associated to Hepatitis E Seroprevalence in Liver Transplant Recipients and Correlates With Altered Immune Markers in Serum: 2017 Presidential Poster Award

Abstract

Introduction: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in immunocompetent hosts as well as liver failure in pregnant women. Recent reports indicate that HEV can lead to chronic infection or acute reactivation in immunocompromised subjects, particularly transplant recipients. A recent study showed that a mutation in the progesterone receptor named PROGINS could confer a higher risk of fulminant hepatic failure by HEV in pregnant women. This mutation is thought to affect the host's immune response to HEV. We have recently shown that the PROGINS mutation is expressed with a higher frequency in individuals with the human immunodeficiency virus who are seropositive for HEV. In this study we studied the frequency of the PROGINS mutations in liver transplant recipients seropositive for HEV. Methods: We evaluated the presence of PROGINS in liver transplant recipients and its relation to HEV infection. Serum samples from 69 individuals who received a liver transplantation were analyzed for the presence of PROGINS through KASP assay. A group of 187 healthy samples were used as controls. Of the 69 transplant recipients, 46 were HEV IgG negative and 23 HEV IgG positive. In a subset of samples, multiplex cytokine assays were performed to compare levels among liver transplant recipients with and without the PROGINS mutation. Results: We found the frequency of PROGINS in transplant recipients HEV-positive to be 35%, compared to 15% in those that were HEV-negative (RR 2.2, CI 0.9-5.5). The frequency of the mutation in the HEV-negative group was similar to that in healthy controls (14%). When we compared serum levels of multiple immune markers among a subgroup of liver transplant recipients with HEV and the presence of PROGINS (N: 7 each group), we found reduced levels of MIG, APRIL and SCF, as well as increased levels of Eotaxin 3 and IL-31, when compared to liver transplant recipients negative for HEV with wild type progesterone receptor. Conclusion: Our results from a small cohort of liver transplant recipients show a strong trend towards an increased frequency of the PROGINS mutations among those that are seropositive for HEV. These patients expressed altered serum levels of multiple immune markers when compared to those without PROGINS. A study with a larger validation cohort is on the way to confirm this finding and examine its implications.