title: Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study.
abstract: BACKGROUND
  The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved.
  
  
  OBJECTIVE
  To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion.
  
  
  METHODS
  Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls.
  
  
  METHODS
  Level of ATP 1 hour after fructose infusion in patients vs controls.
  
  
  RESULTS
  In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P<.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = -0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery.
  
  
  CONCLUSIONS
  These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Cortez-Pinto
authors.forename: J
authors.initials: J
authors.lastname: Chatham
authors.forename: V P
authors.initials: VP
authors.lastname: Chacko
authors.forename: C
authors.initials: C
authors.lastname: Arnold
authors.forename: A
authors.initials: A
authors.lastname: Rashid
authors.forename: A M
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D015992:Body Mass Index; D005234:Fatty Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018709:Statistics, Nonparametric
chemical_list: D000255:Adenosine Triphosphate