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.
Eur J Clin Invest. 2016 Jul;46(7):627-35. doi: 10.1111/eci.12639. Epub 2016 Jun 9.
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.
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.
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).
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.
肝脏再生需要大量的能量供应。实验证据表明，线粒体功能对肝脏再生至关重要。然而，这在临床环境中尚未得到研究。我们旨在：（i）评估肝切除术中线粒体功能的变化，尤其是在肝蒂夹闭后；（ii）将这些变化与术后肝细胞功能和临床结果相关联。
对 30 例接受肝切除术的患者进行前瞻性研究。测量非切除肝实质术中肝活检的线粒体膜电位、呼吸和三磷酸腺苷含量。将结果与肝蒂夹闭时间、术后肝细胞坏死和功能标志物（转氨酶、动脉乳酸、国际标准化比值、胆红素）以及发病率相关联。
肝蒂夹闭时间较长与线粒体去极化程度更差（r = -0.519；P = 0.011）和延迟期更长相关（r = 0.568；P = 0.006）。术后峰值转氨酶、国际标准化比值和胆红素越高，与线粒体功能越差相关（P < 0.05）。在大肝切除术后，线粒体呼吸与术后动脉乳酸清除率相关（r = 0.756；P = 0.049）。有肝特异性并发症和术后肝功能衰竭的患者线粒体生物能量参数显著降低（P < 0.05）。多变量分析显示，线粒体电位下降是肝特异性并发症的独立危险因素（OR = 13.7；P = 0.043）。延迟期较长是肝切除术后肝功能衰竭的高度预测因素（曲线下面积：0.933；P = 0.008）。
线粒体功能、肝蒂夹闭时间与肝切除术后临床结果之间存在相关性。线粒体生物能量学有可能转化为临床实践，有助于更早诊断术后肝功能障碍，并作为未来药物治疗的靶点。
