title: Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature.
abstract: OBJECTIVE
  Hepatitis E virus (HEV) infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million, with approximately 56 000 deaths. As with other viral hepatitides, extra-hepatic manifestations could represent an important aspect of this infection. The spectrum of these manifestations is still emerging. Acute pancreatitis and neurological, musculoskeletal, hematological, renal, and other immune-mediated manifestations have been described. The aim of this article is to comprehensively review the published literature of extra-hepatic manifestations associated with HEV infection.
  
  
  METHODS
  We searched the PubMed database using the MeSH term "hepatitis E" and each of the extra-hepatic manifestations associated with HEV infection. No language or date restrictions were set in these searches. Searches retrieving articles with non-A, non-B hepatitis were excluded. Additional articles were identified through the reference lists of included articles.
  
  
  RESULTS
  Several extra-hepatic manifestations associated with HEV infection have been published. The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them. According to the available data, HEV infection appears to be strongly associated with acute pancreatitis, neurological disorders (with primarily dominant peripheral nerve involvement, most commonly manifested as Guillain-Barré syndrome, followed by neuralgic amyotrophy), hematological diseases (hemolytic anemia due to glucose phosphate dehydrogenase deficiency, and severe thrombocytopenia), glomerulonephritis, and mixed cryoglobulinemia. More data are needed to clarify whether an association exists with musculoskeletal or other immune-mediated manifestations.
  
  
  CONCLUSIONS
  HEV infection should be considered in patients with acute pancreatitis, Guillain-Barré syndrome, neuralgic amyotrophy, hemolytic anemia due to glucose phosphate dehydrogenase deficiency, severe thrombocytopenia, glomerulonephritis, and mixed cryoglobulinemia. Alternatively, signs and symptoms of these conditions should be sought in patients with acute or chronic HEV infection. More data are needed to confirm the role of HEV in other extra-hepatic disorders.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Fateh
authors.initials: F
authors.lastname: Bazerbachi
authors.affiliation: Department of Gastroenterology and Hepatology, University of Damascus, Damascus, Syrian Arab Republic.
authors.forename: Samir
authors.initials: S
authors.lastname: Haffar
authors.affiliation: Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Garg
authors.affiliation: Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA lakex009@umn.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Lake
keywords: extra-hepatic manifestations; hepatitis E virus; primary prevention; vaccine; viral hepatitis