Increased HEV seroprevalence in patients with autoimmune hepatitis.
BACKGROUND
Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown.


METHODS
969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides.


RESULTS
HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive.


CONCLUSIONS
Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Sven
S
Pischke
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Anett
A
Gisa
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Pothakamuri Venkata
PV
Suneetha
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Steffen Björn
SB
Wiegand
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Richard
R
Taubert
Institute for Pathology, Hannover Medical School, Hannover, Germany.
Jerome
J
Schlue
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Karsten
K
Wursthorn
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Heike
H
Bantel
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Regina
R
Raupach
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Birgit
B
Bremer
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Behrend Johann
BJ
Zacher
Department of Clinical Immunology, Hannover Medical School, Hannover, Germany.
Reinhold Ernst
RE
Schmidt
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Michael Peter
MP
Manns
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Kinan
K
Rifai
Department of Clinical Immunology, Hannover Medical School, Hannover, Germany.
Torsten
T
Witte
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Heiner
H
Wedemeyer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D060085:Coinfection; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood*; D006509:Hepatitis B / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D016751:Hepatitis E / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D016752:Hepatitis E virus / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D006521:Hepatitis, Chronic; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016036:Seroepidemiologic Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D006508:Hepatitis Antibodies; D012367:RNA, Viral