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Eur J Clin Invest. 2016 Jul;46(7):627-35. doi: 10.1111/eci.12639. Epub 2016 Jun 9.

Mitochondrial bioenergetics and posthepatectomy liver dysfunction.

Author information

1
Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
2
Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
3
Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
4
Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
5
Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

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.

MATERIALS AND 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.

KEYWORDS:

Bioenergetics; hepatectomy; liver failure; mitochondria

PMID:
27138992
DOI:
10.1111/eci.12639
[Indexed for MEDLINE]

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