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

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.

Evidence of a Link between Hepatitis E Virus Exposure and Glomerulonephritis Development

“…Furthermore, Taton et al reported that HEV infection was the causative agent of de novo membranous nephropathy that developed in a patient who underwent kidney transplantation [ 38 ]. On the other hand, Pischke and colleagues reported that past exposure to HEV-3 infection in German patients was not linked to the development of GN in general but could link to membranoproliferative glomerulonephritis [ 11 ].…”

“…These results suggest that exposure to HEV could be a risk factor for renal complications such as GN. On the other hand, Pischke and colleagues reported that the percentages of anti-HEV IgG among GN and healthy subjects were 22% and 29%, respectively, in regions endemic to HEV-3 [ 11 ]. Since there were no significant differences in HEV seropositivity between both groups, the authors hypothesized that there was no link between past HEV-3 exposure and GN development in general [ 11 ].…”

“…Probably the seropositive GN patients developed HEV infections during their life and this could explain these findings, but further studies should be performed to ascertain these points. Similarly, Pischke et al showed that anti-HEV positive-GN patients had higher bilirubin levels compared to seronegative GN patients [ 11 ]. However, in the previous report, seropositive GN patients were older and had higher creatinine levels (reduced glomerular filtration rate) compared to seronegative GN patients [ 11 ].…”

“…Several studies confirmed the possible association between HEV infection and the development of GN during acute and chronic phases of HEV infections [ 3 , 5 , 10 ]. However, Pischke et al showed that there is no link between previous exposure to HEV-3 and the development of GN in general [ 11 ]. Regarding HEV genotype 1 (HEV-1), limited data were linked to renal disorders.…”

A HEV ORF2 protein-mediated mechanism of hepatitis E-associated kidney disease

“…Glomerular HEV ORF2 protein depositions might have been an aggravating factor. Nevertheless, it is conceivable that in addition to cases of fully developed glomerulonephritis 6,[9][10][11] , as in patient 1, glomerular damage associated with more subtle HEV-ORF2 protein deposits, as in patients 2-4, may represent a general early morphological correlate and harbinger of impaired glomerular function in the context of HEV infection.…”