title: Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy.
abstract: OBJECTIVE
  Acute liver insufficiency is a rare complication of anorexia nervosa. The mechanisms for this complication are unclear. The aim of this study was to describe patient characteristics and clarify the mechanisms involved.
  
  
  METHODS
  Liver specimens from 12 patients (median age, 24 years; median body mass index, 11.3 kg/m(2)), with a prothrombin index <50% and/or an International Normalized Ratio >1.7 and anorexia nervosa as the only cause for acute liver injury were analyzed. A detailed pathologic examination was performed, including under electron microscopy.
  
  
  RESULTS
  Liver cell glycogen depletion was a constant finding. There was a contrast between the increase in serum alanine aminotransferase (56 times normal on average; 1,904 IU/L) and the absence of significant hepatocyte necrosis on histology. Centrilobular changes (trabecular atrophy and/or sinusoidal fibrosis) were observed in 6 patients. There were rare or no (<5%) terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes, suggesting that apoptosis was not the primary mechanism. Hepatocytes from 4 patients showed numerous autophagosomes, a morphologic hallmark of autophagy, on electron microscopy. In contrast, the mitochondria, endoplasmic reticulum, and nuclei were normal in most cells. These features were absent in 11 control patients. The outcome was favorable in all patients, with a rapid return to normal liver function.
  
  
  CONCLUSIONS
  Anorexia nervosa with extremely poor nutritional status should be added to the list of conditions causing acute liver insufficiency. Our findings show that starvation-induced autophagy in the human liver may be involved in liver cell death during anorexia nervosa, even though other mechanisms of liver cell damage could also play a role.
authors.affiliation: Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Rautou
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals-Hatem
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Claire
authors.initials: C
authors.lastname: Francoz
authors.forename: Gérard
authors.initials: G
authors.lastname: Feldmann
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Eric
authors.initials: E
authors.lastname: Ogier-Denis
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Dominique
authors.initials: D
authors.lastname: Valla
authors.forename: François
authors.initials: F
authors.lastname: Durand
mesh_terms: D000208:Acute Disease; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017209:Apoptosis; D029681:Arabidopsis Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D048550:Hepatic Insufficiency / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D020287:In Situ Nick-End Labeling; D008112:Liver Glycogen / Q000378:metabolism; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D021382:Protein Sorting Signals; D013217:Starvation / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029681:Arabidopsis Proteins; D000071186:Beclin-1; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008112:Liver Glycogen; D018832:Molecular Chaperones; D009842:Oligopeptides; D021382:Protein Sorting Signals; C519561:beclin 1 protein, Arabidopsis; C073762:lysyl-aspartyl-glutamyl-leucine