Increased seroprevalence of HAV and parvovirus B19 in children and of HEV in adults at diagnosis of autoimmune hepatitis

Richard Taubert,Elmar Jaeckel,Jana Diestelhorst,Ulrich Baumann,Michael P Manns,Heiner Wedemeyer,Sven Pischke,Arndt Vogel,Martha M Kirstein,Heike Bantel,Norman Junge

doi:10.1038/s41598-018-35882-7

Abstract

Preceding viral infections have mostly been described in autoimmune hepatitis (AIH) in single cases. We aimed to identify viral infections that potentially trigger AIH, as suggested for hepatitis E virus (HEV) infections. Therefore, antibodies against hepatitis A (HAV), B, C and E viruses; hepatotropic herpesviruses; and parvovirus B19 (PVB19) were analyzed retrospectively in 219 AIH patients at diagnosis, 356 patients with other liver diseases and 89 children from our center. Untreated adult AIH (aAIH) patients showed higher anti-HEV seroprevalences at diagnosis than patients with other liver diseases. Untreated aAIH patients had no increased incidence of previous hepatitis A, B or C. Antibodies against hepatotropic herpesviruses in untreated AIH were in the range published for the normal population. Untreated pediatric AIH (pAIH) patients had evidence of more previous HAV and PVB19 infections than local age-matched controls. The genetic AIH risk factor HLA DRB1*03:01 was more frequent in younger patients, and DRB1*04:01 was more frequent in middle-aged patients without an obvious link to virus seropositivities. Pediatric and adult AIH seem to be distinct in terms of genetic risk factors and preceding viral infections. While associations cannot prove causal relations, the results suggest that hepatotropic virus infections could be involved in AIH pathogenesis.

Highlights

Autoimmune hepatitis (AIH) is an immune-mediated liver disease that affects all age groups with an increasing incidence and prevalence[1]
Only one pediatric cohort has been analyzed for antibodies against the herpes simplex virus (HSV) and the hepatitis C virus (HCV)[10]
In untreated autoimmune hepatitis (AIH) patients diagnosed at 40 years and older, anti-hepatitis E virus (HEV) IgG antibodies were significantly more often detected compared to non-AIH liver diseases

Summary

Introduction

Autoimmune hepatitis (AIH) is an immune-mediated liver disease that affects all age groups with an increasing incidence and prevalence[1]. The only human genetic risk factors that could be confirmed by a large multicenter genome-wide association study were MHC class II molecules[5]. Environmental factors such as drugs and preceding viral infections, which have been suggested to act as external triggers of AIH, were much more diverse[6]. Anti-PVB19 untreated AIH pediatric local pediatric control population could not be confirmed in a multicenter study in the neighboring Netherlands[12] Both studies could potentially be biased by (I) not focusing on the time of AIH diagnosis but rather testing at any time and (II) by not excluding overlap syndromes with other autoimmune liver diseases. The present study used a comprehensive approach by determining the prevalence of antibodies against specific hepatitis viruses, hepatotropic herpesviruses and parvovirus B19 (PVB19) in pediatric and adult AIH patients at the time of diagnosis before the start of an AIH-specific treatment

Objectives

Methods

Results

Conclusion