Autochthonous acute hepatitis E: an increasingly frequent diagnosis. Clinical-epidemiological analysis of our experience

Abstract

Background: In Europe, acute hepatitis caused by the hepatitis E virus (HEV) traditionally was an infection found in people who had travelled to endemic zones, mainly Asia and Africa. However, a growing number of sporadic autochthonous cases are now being diagnosed in the Western world.Objective: To analyze the cases of acute HEV hepatitis diagnosed in our setting, with the identification of the clinicalepidemiological characteristics. Material and methods:We included the cases of acute HEV hepatitis diagnosed (positive anti-HEV IgM and/or HEV RNA present in serum) between January 2008 and December 2014. Different clinical, epidemiological and evolutive parameters were analyzed.Results: A total of 23 patients were identified, all originating from Spain. Fourteen cases (60.87%) presented jaundice and marked cytolysis at the time of diagnosis (aspartate aminotransferase [AST] 1,106.91 U/l and alanine aminotransferase [ALT] 1,407.04 U/l). Twenty-two cases were regarded as autochthonous, and one patient had travelled to China three months before. The mean time to resolution was 11.2 weeks. Some autoimmune markers were positive in 43.5% of the patients. Two subjects were diagnosed with previous chronic liver disease and were classified as "acuteon-chronic liver failure" (ACLF), one died and the other underwent liver transplantation.Conclusion: Acute HEV hepatitis in our setting is an autochthonous condition that is probably underdiagnosed, manifesting with jaundice and cytolysis. Autoimmune marker positivity is an epiphenomenon, which in some cases complicates the diagnosis.

Autoimmune liver disease serology in acute hepatitis E virus infection

“…Autoantibody positivity, in particular in respect to SMA, is not unusual during the course of viral hepatitis, having been reported for hepatitis A, B, C and E [19,[25][26][27][28][29]. Usually, in the course of viral hepatitis SMA displays the non-specific V pattern [23], as detected in most of our HEV patients, and its presence is considered non-specific, though autoantibody positivity has been associated with more severe disease in chronic hepatitis C [30].…”

“…In the first report, a patient with acute HEV infection and positive ANA (IIF pattern not specified) was diagnosed with classical AIH five months after the acute episode, on the basis of chronic fatigue, negative HEV RNA in the blood, persistently elevated transaminase and IgG levels, positive ANA (1:640, pattern not reported) and typical histological findings [21]. A diagnosis of AIH following acute HEV infection is reported also in the Spanish series, in an ANA positive patient (pattern not described) with a prolonged hepatitis course despite clearance of HEV virus and liver histology compatible with AIH [28].…”

“…That HEV can trigger or unmask AIH is suggested by two reports, one from Japan and one from Spain [21,28]. In the first report, a patient with acute HEV infection and positive ANA (IIF pattern not specified) was diagnosed with classical AIH five months after the acute episode, on the basis of chronic fatigue, negative HEV RNA in the blood, persistently elevated transaminase and IgG levels, positive ANA (1:640, pattern not reported) and typical histological findings [21].…”

“…Evolution from HAV, HCV and HEV infection to overt AIH has been anecdotally described [12,21,28,31,32], raising the question as to whether these viruses could be involved in the development of AIH and whether detection of autoantibodies typical of AIH during acute viral infection may herald progression to autoimmune liver disease. Such an evolution has been documented for AIH type 2 in an instructive case report, where primary and secondary anti-LKM1 immune response after acute HCV infection prefigured the onset of overt AIH nine years later [12].…”

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

“…In addition to cause hepatic inflammation and chronic liver disease, viral infections have been addressed as potential triggers of AIH. 3 In this respect, Hepatitis A-,B-,C, [4][5][6][7][8] Measles, 9 Cytomegalo,10 Epstein-Barr, 11 Herpes simplex 10 as well as Hepatitis E virus infection 12,13 were suggested to play a role in the pathogenesis of AIH.…”