Lack of Evidence for an Association between Previous HEV Genotype-3 Exposure and Glomerulonephritis in General.

Sven Pischke,Oliver M Steinmetz,Marylyn M Addo,Jan E Turner,Christine Petersen-Benz,Thomas Horvatits,Maria Mader,Christian F Krebs,Tilman Schmidt,Julian Schulze Zur Wiesch,Sarah Tamanaei,Munif Haddad,Tobias B Huber,Elion Hoxha

doi:10.3390/pathogens11010018

Abstract

Among numerous other immune-mediated diseases, glomerulonephritis has also been suspected to be an extrahepatic manifestation of HEV infection. In this prospective study, we tested 108 patients with glomerulonephritis and 108 age- and sex-matched healthy controls at the University Hospital Hamburg Eppendorf, Hamburg, Germany, for anti-HEV IgG (Wantai test) as a marker for previous HEV exposure. A total of 24 patients (22%) tested positive for anti-HEV IgG. Males tended to be more frequently anti-HEV IgG positive (29%) in comparison to females (16%). However, this does not reach statistical significance (p = 0.07). Anti-HEV IgG positive patients were older in comparison to negative patients (mean 53 vs. 45 years, p = 0.05). The kidney function seems to be slightly decreased in anti-HEV IgG positive patients in comparison to and anti-HEV IgG negative patients basing on creatinine (p = 0.04) and glomerular filtration rate (GFR) (p = 0.05). Slightly higher values of bilirubin could be found in IgG positive patients (p = 0.04). Anti-HEV-IgG seropositivity rate (22%) in glomerulonephritis patients, did not differ significantly in comparison to an age- and sex-matched control cohort of healthy blood donors (31/108 positive, 29%). A total of 2/2 patients with membranoproliferative glomerulonephritis (MPGN) tested anti-HEV IgG positive (p = 0.002 in comparison to glomerulonephritis patients with other subtypes). In conclusion, our findings indicate that previous HEV exposure in a region where GT3 is endemic is not associated with glomerulonephritis in general. However, the subgroup of MPGN patients should be investigated in future studies. Furthermore, future studies are needed to investigate whether the observed association between anti-HEV IgG positivity and reduced GFR in glomerulonephritis patients is HEV associated or is an age-related effect.

Highlights

Hepatitis E virus (HEV) infections have been shown to be associated with a large variety of assumed extrahepatic manifestations
A comparison of the variables of anti-HEV IgG positive and anti-HEV IgG negative glomerulonephritis patients revealed lower values for glomerular filtration rate (GFR) (p = 0.05), albumin/creatinine ratio in urine (p = 0.01) and protein in urine (p = 0.04) while significantly higher values were found for creatinine (p = 0.04), and bilirubin (p = 0.04, Figure 1)
Seroprevalence in the healthy control cohort or the rate in conditions, it is still unclear whether HEV infections, similar to HBV or HCV infections, glomerulonephritis patients with other subtypes

Summary

Introduction

Hepatitis E virus (HEV) infections have been shown to be associated with a large variety of assumed extrahepatic manifestations. Disorders, and renal affection has been assumed to be caused or triggered by HEV infections. A scientifical proof of a causal relationship is still lacking. One of these diseases, which has been associated with HEV infections and has been assumed to be an extrahepatic manifestation is glomerulonephritis. Glomerulonephritis has been shown to be potentially triggered by hepatitis C or B virus infections and is sometimes associated with cryoglobulinemia, a distinct immunological phenomenon [3]. Similar mechanisms have been hypothesized for HEV infections and renal manifestations [5]

Methods

Results

Conclusion