title: Severe and fulminant hepatitis of indeterminate etiology in a Japanese center.
abstract: OBJECTIVE
  The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF.
  
  
  METHODS
  We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively.
  
  
  RESULTS
  Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients.
  
  
  CONCLUSIONS
  There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies.
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Shin
authors.initials: S
authors.lastname: Yasui
authors.affiliation: Division of Pathology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yonemitsu
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology, Seikeikai Chiba Medical Center, Chiba.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
authors.affiliation: Departments of Gastroenterology and Nephrology.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
keywords: acute liver failure; fulminant hepatitis; severe hepatitis; unknown etiology