title: Acetaminophen metabolism after liver resection: A prospective case-control study.
abstract: BACKGROUND
  The effect of liver resection on acetaminophen metabolism and whether it is affected by residual liver volume is poorly understood.
  
  
  METHODS
  We investigated the effects of liver resection on acetaminophen metabolism in a single centre, prospective observational, case-control study of inpatients. Patients undergoing liver resection were administered therapeutic post-operative acetaminophen. Glutathione and urinary acetaminophen metabolites were measured over the first three post-operative days and compared between patients with low (Group A) and high (Group B) residual liver volume.
  
  
  RESULTS
  41 patients (41% female, median age 62 [IQR 53-72] years) were included. Mean urinary cysteine levels increased significantly from post-operative day 1 to 2 (578.0 mg/day 95% CI 478.9-677.1 vs. 775.4 mg/day, 95% CI 625.7-925.1; p=0.03). Group A (n=11) had significantly higher median levels of cysteine (day 1, 464.3 mg/day [IQR 355.6-582.0]; day 3, 717.6 mg/day [IQR 423.5-1104.0]) compared to Group B (n=11): day 1, 545.4 mg/day (IQR 346.9-843.5); day 3, 508.1mg/day (IQR 390.8-788.4; p=0.048). No significant difference was observed in glutathione or 5-oxoproline levels between the groups.
  
  
  CONCLUSIONS
  Low residual liver volume results in altered acetaminophen metabolism, however, no evidence of glutathione deficiency was observed. Therapeutic acetaminophen is safe after major liver resection provided liver function is adequate.
authors.affiliation: Department of Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. Electronic address: michaelh@doctors.net.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hughes
authors.affiliation: Department of Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ewen M
authors.initials: EM
authors.lastname: Harrison
authors.affiliation: CRF Mass Spectrometry Core, Centre for Cardiovascular Science, Level 3, East Block, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Jin
authors.affiliation: CRF Mass Spectrometry Core, Centre for Cardiovascular Science, Level 3, East Block, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Homer
authors.affiliation: Department of Clinical Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wigmore
mesh_terms: D000082:Acetaminophen / Q000097:blood* / Q000652:urine*; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003545:Cysteine / Q000652:urine*; D005260:Female; D005978:Glutathione / Q000652:urine*; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D000082:Acetaminophen; D005978:Glutathione; D003545:Cysteine
keywords: Acetaminophen metabolism; Hepatotoxicity; Liver resection