High seroprevalence of anti‐Hepatitis E antibodies in Austrian patients with autoimmune hepatitis

Abstract

Background & Aims Increasing numbers of autochthonous hepatitis E virus infections have been reported in Europe. Chronic infections have been shown in immune‐compromised patients after solid organ transplantation. Hepatitis E virus might be a possible trigger for autoimmune hepatitis and might cause disease flares or relapses in the further course of disease. Aim of this study was to investigate the presence of hepatitis E virus antibodies and hepatitis E virus RNA, and to analyse their impact on immunosuppressive treatment in patients with autoimmune hepatitis. Methods Sera from 92 autoimmune hepatitis patients (73/79.3% female, age: 42.2 ± 16.3 years [mean ± SD]) were tested. Patients were scored according to the simplified and revised scoring systems of the International Autoimmune Hepatitis Group. The prevalence of anti‐ hepatitis E virus antibodies (Beijing Wantai Biological Pharmacy Enterprises Co., Ltd, Beijing, China) and hepatitis E virus RNA was determined. Results 19/20.7% autoimmune hepatitis patients tested positive for hepatitis E virus‐IgG, which was higher than in previous reports of healthy Austrian individuals (12.4%, P = 0.031); hepatitis E virus RNA was not detectable in any patient. Anti‐hepatitis E virus positive patients were older (49.5 ± 9.5 vs 40.4 ± 17.2 years [mean ± SD], P = 0.033) but did not differ in laboratory findings at diagnosis (AST: 14.6 [1.3‐70.6] vs 9.5 [0.7‐62.7] × ULN [median/range]; P = 0.387, alanine aminotransferase: 18.3 [1.6‐62.7] vs. 12.9 [0.8‐62.6] × ULN; P = 0.511; IgG: 1.4 [1.0‐2.5] vs 1.3 [0.6‐3.8] g/dL × ULN; P = 0.278) nor in alanine aminotransferase levels after six months (0.7 [0.5‐2.4] vs 1.0 U/L × ULN [0.1‐22.4]; P = 0.077). Conclusions No chronic hepatitis E virus infection was observed in our cohort of autoimmune hepatitis patients. Anti‐ hepatitis E virus‐IgG positive patients were older and the seroprevalence was nearly twice as high as reported previously in healthy Austrian individuals, suggesting that hepatitis E virus‐infection might act as trigger for the development of autoimmune hepatitis.

Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false‐positive antibodies

“…Several studies have assessed the prevalence of anti-HEV IgG antibodies in patients with AIH, which was found to be higher than that of the general local population. [12][13][14] These data raised the question as to whether a past HEV infection could be linked to the development of AIH as has previously been described with HEV and other viral infections. 2,4,5,21,22 In our area, the seroprevalence of HEV has been estimated to range between 7% 8 and 11%, 10 similar to what we found in patients with chronic AIH (10%).…”

“…Briefly, patients with chronic AIH (n = 50) were mostly female (33, 66%) with a median age of 47 years (32-61). Laboratory test results at diagnosis were: ALT 652 international units (IU) (IQR: 321-1612), AST 561 IU/L (IQR: 301-1503), total bilirubin 3.1 mg/dL (IQR: 1-9.3) and serum IgG levels 18 g/L (IQR: [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Thirty-three patients (66%) presented positive ANA with a median titre of 1:320 (1:80-1:640), 1 patient had positive anti-LKM (2%), 1 anti-SLA (2%) and 31 (62%) ASMA with a median titre of 1:80 (1:40-1:160).…”

“…11 Several recent studies have evaluated the seroprevalence of HEV in patients diagnosed with AIH being it higher than in general population in their area and thus hypothesized that HEV infection might trigger the development of AIH. [12][13][14] However, it is also possible that the higher HEV seroprevalence reported in previous studies merely reflects the presence of false-positive IgG antibodies in the context of the typical hypergammaglobulinemia found in AIH patients. Therefore, in the current study we aimed to assess the prevalence of positive anti-HEV IgM and IgG and HEV-RNA in a cohort of AIH patients followed in a Catalan tertiary hospital to determine the impact of positive HEV serology (and/or HEV-RNA) on patient outcome and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology.…”

A case of acute liver failure due to hepatitis E virus, liver transplantation, and development of de novo autoimmune hepatitis

“…Moreover, HEV has been suggested as a potential trigger of AIH by Le Cann et al in 1997 11,12 . Recently, a German and an Austrian study supported this hypothesis by showing a higher anti‐HEV IgG prevalence in AIH patients compared to that in the general population 12,13 .…”

“…Moreover, HEV has been suggested as a potential trigger of AIH by Le Cann et al in 1997 11,12 . Recently, a German and an Austrian study supported this hypothesis by showing a higher anti‐HEV IgG prevalence in AIH patients compared to that in the general population 12,13 . However, a larger Dutch study showed no significant difference in the anti‐HEV prevalence between AIH patients and the general population; thus, this association remains controversial 14 .…”