Bioenergetic adaptations of the human liver in the ALPPS procedure – how liver regeneration correlates with mitochondrial energy status

Alexandrino, Henrique; Rolo, Anabela P.; Donato, Henrique; Martins, Ricardo; Serôdio, Marco; Martins, Martinho A. S.; Tralhão, José Guilherme; Caseiro-Alves, Filipe; Palmeira, Carlos M.; Sousa, F. Castro e

doi:10.1016/j.hpb.2017.08.005

Cited by 11 publications

(9 citation statements)

References 46 publications

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“…47 More recently, we have explored mitochondrial function and biogenesis in twostage hepatectomies with portal vein ligation and confirmed these findings. 50 We found strong and significant correlations between deteriorating mitochondrial energy metabolism and several markers of postoperative liver function, confirming our previous work. Moreover, volumetric regeneration of the liver remnant was also strongly correlated with improved energetic metabolism.…”

Section: Mitochondrial Bioenergetics and Posthepatectomy Liver Dysfsupporting

confidence: 91%

Research update for articles published in EJCI in 2016

Adlbrecht

Blanco-Verea

Bouzas-Mosquera

et al. 2018

Eur J Clin Investigation

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Section: Mitochondrial Bioenergetics and Posthepatectomy Liver Dysfsupporting

confidence: 91%

Research update for articles published in EJCI in 2016

Adlbrecht

Blanco-Verea

Bouzas-Mosquera

et al. 2018

Eur J Clin Investigation

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“…PHP may cause SE cells swelling and detachment by increased shear stress, impede oxygen diffusion and oxygen uptake by the liver tissue (2,3,15). Liver regeneration requires a rich supply of oxygen and energy (16,17), while PHP reduces the oxygen saturation in the liver tissue, limiting the oxygenation of liver cells and reducing the mitochondrial redox function, Dold et al revealed that the injury to mitochondria by PHP following major hepatectomy may be related to oxygen supply and oxygen uptake (13). In that study, hepatic tissue oxygen pressure (pO 2 ) was significantly decreased and was associated with an increased expression of hypoxia-inducible factor-1α (HIF-1α) under conditions of PHP after a 70 and 90% hepatectomy; in line with these findings, 90% hepatectomy also resulted in an increase of NADH fluorescence compared with the baseline, indicating an impaired mitochondrial redox status of the liver tissue.…”

Section: Discussionmentioning

confidence: 99%

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis

et al. 2018

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The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

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“…Liver regeneration requires a rich supply of oxygen and energy (Alexandrino et al, 2017). Higher liver PF values in the fibrotic livers post-PH could have been due to the increased blood supply from the hepatic artery.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Fibrotic Liver Regeneration After Partial Hepatectomy With Intravoxel Incoherent Motion Diffusion-Weighted Imaging: An Experimental Study in a Rat Model With Carbon Tetrachloride Induced Liver Injury

et al. 2022

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PurposeTo determine whether intravoxel incoherent motion (IVIM) parameters correlate with liver regeneration and function recovery after partial hepatectomy (PH) in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.MethodsSixty-two adult Sprague-Dawley rats were divided into the control group and the fibrosis group with CCl4 injection for 8 weeks. At the end of the 8th week, all rats received left lateral lobe liver resection. Within each group, IVIM imaging (n = 10/group) and histologic and biochemical analyses (n = 3/group/time point) were performed pre- and post-PH (on days 1, 2, 3, 5, 7, 14, and 21). Differences in liver IVIM parameters and correlation between IVIM parameters and Ki-67 indices, hepatocyte diameter, alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) values were analyzed.ResultsPost-PH, liver true diffusion coefficient (D) values decreased and pseudodiffusion coefficient (D*) and perfusion fraction (PF) values increased, then recovered to pre-PH levels gradually in both fibrosis and control rats. PF in fibrosis group were significantly higher than in controls from 3 to 21 days (P < 0.05). In fibrosis rats, both Ki-67 indices and hepatocyte diameters increased, and a strong correlation was found between PF and Ki-67 indices (r = −0.756; P = 0.03), D* and PF values and ALT, AST, and TBil values (r = −0.762 to −0.905; P < 0.05). In control rats, only hepatocyte diameters increased, and all IVIM parameters correlated well with hepatocyte diameters, ALT, AST and TBil values (r = 0.810 to −1.000; P < 0.05).ConclusionThe regeneration pattern in fibrotic liver tissue was different compared with control livers. IVIM parameters can monitor liver regeneration and functional recovery non-invasively after PH.

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Bioenergetic adaptations of the human liver in the ALPPS procedure – how liver regeneration correlates with mitochondrial energy status

Abstract: Metabolic capacity in ALPPS is worse than in controls, improves between stages and correlates with volumetric growth. Bioenergetic adaptations in ALPPS could serve as surrogate markers of liver reserve and as target for energetic conditioning.

Cited by 11 publications

References 46 publications

Research update for articles published in EJCI in 2016

Research update for articles published in EJCI in 2016

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis

Assessment of Fibrotic Liver Regeneration After Partial Hepatectomy With Intravoxel Incoherent Motion Diffusion-Weighted Imaging: An Experimental Study in a Rat Model With Carbon Tetrachloride Induced Liver Injury

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