title: Mitochondrial bioenergetics and posthepatectomy liver dysfunction.
abstract: BACKGROUND
  Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome.
  
  
  METHODS
  Prospective study of thirty patients undergoing hepatectomy. Measurement of mitochondrial membrane potential, respiration and adenosine triphosphate content in intra-operative liver biopsies performed in nonresected parenchyma. Correlation of findings with duration of hepatic pedicle clamping, postoperative markers of hepatocellular necrosis and function (aminotransferases, arterial lactate, international normalized ratio, bilirubin), and morbidity.
  
  
  RESULTS
  Longer hepatic pedicle clamping was associated with worse mitochondrial depolarization (r = -0·519; P = 0·011) and longer lag phase (r = 0·568; P = 0·006). Higher postoperative peak aminotransferases, international normalized ratio and bilirubin correlated with worse mitochondrial function (P < 0·05). After major hepatectomy, mitochondrial respiration correlated with postoperative arterial lactate clearance (r = 0·756; P = 0·049). Mitochondrial bioenergetic parameters were significantly decreased in patients with liver-specific morbidity and postoperative liver failure (P < 0·05). On multivariate analysis, decrease in mitochondrial potential was an independent risk factor for liver-specific morbidity (OR = 13·7; P = 0·043). Worse lag phase was highly predictive of posthepatectomy liver failure (area under the curve: 0·933; P = 0·008).
  
  
  CONCLUSIONS
  There is a relationship between mitochondrial function, duration of hepatic pedicle clamping and clinical outcome after hepatectomy. Mitochondrial bioenergetics can potentially translate into clinical practice, assisting in earlier diagnosis of postoperative liver dysfunction, and as a target for future pharmacological therapies.
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.|Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Alexandrino
authors.affiliation: Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.|Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana T
authors.identifier: http://orcid.org/0000-0003-3599-1660
authors.initials: AT
authors.lastname: Varela
authors.affiliation: Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.|Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: João Soeiro
authors.initials: JS
authors.lastname: Teodoro
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.|Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Mónica A
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.|Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Anabela P
authors.initials: AP
authors.lastname: Rolo
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.|Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: José Guilherme
authors.initials: JG
authors.lastname: Tralhão
authors.affiliation: Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.|Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Palmeira
authors.affiliation: Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.|Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Castro E Sousa
mesh_terms: D000236:Adenoma / Q000601:surgery; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000601:surgery; D015179:Colorectal Neoplasms / Q000473:pathology; D004444:Echinococcosis, Hepatic / Q000601:surgery; D004734:Energy Metabolism; D005260:Female; D006498:Hepatectomy; D006801:Humans; D019934:International Normalized Ratio; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000502:physiology / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism*; D015999:Multivariate Analysis; D009336:Necrosis; D011183:Postoperative Complications / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D019344:Lactic Acid; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: Bioenergetics; hepatectomy; liver failure; mitochondria