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

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.

Automated summary

This study examines the relationship between HEV infection and glomerulonephritis. The findings indicate that 22% of glomerulonephritis patients tested positive for anti-HEV IgG, and that positive patients tend to have slightly decreased kidney function and higher bilirubin levels. Furthermore, all patients with MPGN subtype tested positive for anti-HEV IgG. These findings suggest that previous HEV exposure is not generally associated with glomerulonephritis, but may be associated with MPGN. Further studies are needed to investigate this association and determine whether it is HEV-related or age-related.