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Surgery Today

, Volume 44, Issue 9, pp 1611–1625 | Cite as

Ischemia–reperfusion injury in patients with fatty liver and the clinical impact of steatotic liver on hepatic surgery

  • Hirotaka Tashiro
  • Shintaro Kuroda
  • Yoshihiro Mikuriya
  • Hideki Ohdan
Review Article

Abstract

Hepatic steatosis is one of the most common hepatic disorders in developed countries. The epidemic of obesity in developed countries has increased with its attendant complications, including metabolic syndrome and non-alcoholic fatty liver disease. Steatotic livers are particularly vulnerable to ischemia/reperfusion injury, resulting in an increased risk of postoperative morbidity and mortality after liver surgery, including liver transplantation. There is growing understanding of the molecular and cellular mechanisms and therapeutic approaches for treating ischemia/reperfusion injury in patients with steatotic livers. This review discusses the mechanisms underlying the susceptibility of steatotic livers to ischemia/reperfusion injuries, such as mitochondrial dysfunction and signal transduction alterations, and summarizes the clinical impact of steatotic livers in the setting of hepatic resection and liver transplantation. This review also describes potential therapeutic approaches, such as ischemic and pharmacological preconditioning, to prevent ischemia/reperfusion injury in patients with steatotic livers. Other approaches, including machine perfusion, are also under clinical investigation; however, many pharmacological approaches developed through basic research are not yet suitable for clinical application.

Keywords

Steatotic liver Ischemia–reperfusion injury Rho-kinase 

References

  1. 1.
    Kleiner DE, Brunt EM, Natta MV, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.PubMedGoogle Scholar
  2. 2.
    Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:E462–8.PubMedGoogle Scholar
  3. 3.
    Chittu S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol. 2007;22:778–87.Google Scholar
  4. 4.
    Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL. How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J Gastroenterol Hepatol. 2007;22:788–93.PubMedGoogle Scholar
  5. 5.
    Petrowsky H, McCormack L, Trujillo M, Selzner M, Jochum W, Clavian PA. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Ann Surg. 2006;244:921–8.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Angulo P. Nonalcoholic fatty liver disease and liver transplantation. Liver Transpl. 2006;12(523–534):5.Google Scholar
  7. 7.
    McCormack L, Petrowsky H, Jochum W, Furrer K, Clavien PA. Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case–control study. Ann Surg. 2007;245:923–30.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Gomez D, Malik HZ, Bonney GK, Wong V, Toogood GJ, Lodge JP, et al. Steatosis predicts postoperative morbidity following hepatic resection for colorectal metastasis. Br J Surg. 2007;94:1395–402.PubMedGoogle Scholar
  9. 9.
    Trevisani F, Colantoni A, Caraceni P, Van Thiel DH. The use of donor fatty liver for liver transplantation: a challenge or a quagmire? J Hepatol. 1996;24:114–21.PubMedGoogle Scholar
  10. 10.
    Hui AM, Kawasaki S, Makuuchi M, Nakayama J, Ikegami T, Miyagawa S. Liver injury following normothermic ischemia in steatotic rat liver. Hepatology. 1994;20:1287–93.PubMedGoogle Scholar
  11. 11.
    Wada K, Fujimoto K, Fujikawa Y, Shibayama Y, Mitsui H, Nakata K. Sinusoidal stenosis as the cause of portal hypertension in choline deficient diet induced fatty cirrhosis of the rat liver. Acta Pathol Jpn. 1974;24:207–17.PubMedGoogle Scholar
  12. 12.
    Caraceni P, Ryu HS, Subbotin V, De Maria N, Colantoni A, Roberts L, et al. Rat hepatocytes isolated from alcohol-induced fatty liver have an increased sensitivity to anoxic injury. Hepatology. 1997;25:943–9.PubMedGoogle Scholar
  13. 13.
    Nanashima A, Abo T, Hamasaki K, Wakata K, Kunizaki M, Tou K, et al. Predictors of intraoperative blood loss in patients undergoing hepatectomy. Surg Today. 2013;43:485–93.PubMedGoogle Scholar
  14. 14.
    Lentsch A, kato A, Yoshidome H, McMasters K, Edwards M. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion. Hepatology. 2000;32:169–73.PubMedGoogle Scholar
  15. 15.
    Selzner M, Rudiger HA, Sindram D, Madden J, Clavien PA. Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology. 2000;32:1280–8.PubMedGoogle Scholar
  16. 16.
    Malhi H, Gores G, Lemasters JJ. Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology. 2006;43:S31–44.PubMedGoogle Scholar
  17. 17.
    Selzner N, Selzner M, Jochum W, Amann-Vesti B, Graf R, Clavien PA. Mouse livers with macrosteatosis are more susceptible to normothermic ischemic injury than those with microsteatosis. J Hepatol. 2006;44:694–701.PubMedGoogle Scholar
  18. 18.
    Vetelaninen R, Van Vliet A, Gouma DJ, Van Gulik TM. Steatosis as a risk factor in liver surgery. Ann Surg. 2007;245:20–30.Google Scholar
  19. 19.
    Caraceni P, Bianchi C, Domenicali M, Pertosa AM, Maiolini E, Parenti G, et al. Impairment of mitochondrial oxidative phosphorylation in rat fatty liver exposed to preservation-reperfusion injury. J Hepatol. 2004;41:82–8.PubMedGoogle Scholar
  20. 20.
    Echtay K, Winkler E, Frischmuth K, Klingenberg M. Uncoupling protein 2 and 3 are highly active H+ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Proc Natl Acad Sci USA. 2001;98:1416–21.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Echtay K, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, et al. Nature. 2002;415:96–9.PubMedGoogle Scholar
  22. 22.
    Cortez-Pinto H, Lin HZ, Yang SQ, Costa SOD, Diehl AM. Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes. Gastroenterology. 1999;116:1184–93.PubMedGoogle Scholar
  23. 23.
    Rashid A, Wu TC, Huang CC, Chen CH, Lin HZ, Yang SQ, et al. Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver. Hepatology. 1999;29:1131–8.PubMedGoogle Scholar
  24. 24.
    Chavin KD, Yang SQ, Lin HZ, Chatham J, Chacko VP, Hoek JB, et al. Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem. 1999;274:5692–700.PubMedGoogle Scholar
  25. 25.
    Evans ZP, Ellett JD, Schmit MG, Schnellmann RG, Chavin KD. Mitochondrial uncoupling protein-2 mediates steatotic liver injury following ischemia/reperfusion. J Biol Chem. 2008;283:8573–9.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Serviddio G, Bellanti F, Tamborra R, Rollo T, Capitanio N, Romano AD, et al. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischemia–reperfusion injury. Gut. 2008;57:957–65.PubMedGoogle Scholar
  27. 27.
    Chavin KD, Fiorini RN, Shafizadeh S, Cheng G, Wan C, Evans Z, et al. Fatty acid synthase blockade protects steatotic livers from warm ischemia reperfusion injury and transplantation. Am J Transpl. 2004;4:1440–7.Google Scholar
  28. 28.
    Fiorini RN, Donovan JL, Rodwell D, Evans Z, Cheng G, May HD, et al. Short-term administration of (−)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice. Liver Transpl. 2005;11:298–308.PubMedGoogle Scholar
  29. 29.
    Tolba RH, Putz U, Decker D, Dombrowski F, Lauschke H. l-Carnitine ameliorates abnormal vulnerability of steatotic rat livers to cold ischemic preservation. Transplantation. 2003;76:1681–6.PubMedGoogle Scholar
  30. 30.
    Dara L, Ji C, Kaplowitz N. The contribution of endoplasmic reticulum stress to liver diseases. Hepatology. 2011;53:1752–63.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Tiriveedhi V, Conzen KD, Lian-Conlin JL, Upadhya G, Malone J, Townsend RR, et al. The role of molecular chaperons in warm ischemia and reperfusion injury in the steatotic liver: a proteomic study. BMC Biochem. 2012;13:17–26.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Mosbah IB, Alfany-Fernandez I, Martel C, Zaouali MA, Bintanel-Morcillo M, Rimola A, et al. Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia–reperfusion. Cell Death Dis. 2010;1:e52.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Anderson CD, Upadhya G, Conzen KD, Jia J, Brunt EM, Tiriveedhi V, et al. Endoplasmic reticulum stress is a mediator of posttransplant injury in severely steatotic liver allografts. Liver Transpl. 2011;17:189–200.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Elias-Miro M, Jimenez-Castro MB, Mendes-Braz M, Casillas-Ramirez A, Peralta C. The current knowledge of the role of PPAR in hepatic ischemia–reperfusion injury. PPAR Res. 2012;2012:802384.Google Scholar
  35. 35.
    Pettinelli P, del Pozo T, Araya J, Rodrigo R, Araya AV, Smok G, et al. Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta. 2009;1792:1080–6.PubMedGoogle Scholar
  36. 36.
    Pettineli O, Videla LA. Up-regulation of PPAR-γ mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J Clin Endocrin Metabol. 2011;96:1424–30.Google Scholar
  37. 37.
    Teoh NC, Williams J, Hartley J, Yu J, McCuskey RS, Farrell GC. Short-term therapy with peroxisome proliferation-activator receptor-α agonist wy-14,643 protects murine fatty liver agonist ischemia–reperfusion injury. Hepatology. 2010;51:996–1006.PubMedGoogle Scholar
  38. 38.
    Massip-Salcedo M, Zaouali MA, Padrissa-Altes S, Casillas-Ramirez A, Rodes J, Rosello-Catafau J, et al. Activation of peroxisome proliferators-activated receptor-αinhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia–reperfusion. Hepatology. 2008;47:461–72.PubMedGoogle Scholar
  39. 39.
    Elias-Miro M, Massip-Salcedo M, Jimenez-Castro M, Peralta C. Does adiponectin benefit steatotic liver transplantation? Liver Transpl. 2011;17:993–1004.PubMedGoogle Scholar
  40. 40.
    Mosbath IB, Rosello-Catafau J, Franco-Gou R, Abdennebi HB, Saidane D, Ramella-Virieux S, et al. Preservation of steatotic livers in IGL-1 solution. Liver Transpl. 2006;12:1215–23.Google Scholar
  41. 41.
    Zaouali MA, Reiter RJ, Padrissa-Altes S, Boncompagni E, Garcia JJ, Ben Abnennebi H, et al. Melatonin protects steatotic and nonsteatotic liver grafts against cold ischemia and reperfusion injury. J Pineal Res. 2011;50:213–21.PubMedGoogle Scholar
  42. 42.
    Man K, Zhao Y, Xu A, Lo CM, Lam KSL, Ng KT, et al. Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival. Am J Transpl. 2006;6:467–76.Google Scholar
  43. 43.
    Elias-Miro M, Massip-Salcedo M, Jimenez-Castro M, Peralta C. Does adiponectin benefit steatotic liver transplantation? Liver Transpl. 2011;17:993–1004.PubMedGoogle Scholar
  44. 44.
    Casillas-Ramirez A, Amine-Zaouali M, Massip-Salcedo M, Padrissa-Altes S, Bintanel-Morcillo M, Ramalho F, et al. Inhibition of angiotensin II action protects rat steatotic livers against ischemia–reperfusion injury. Crit Care Med. 2008;36:1256–66.PubMedGoogle Scholar
  45. 45.
    Casillas-Ramirez A, Zaouali A, Padrissa-Altes S, Ben MI, Pertosa A, Alfany-Fernandez I, et al. Insulin-like growth factor and epidermal growth factor tretament: new approaches to protecting ateatotic livers against ischemia–reperfusion injury. Endocrinology. 2009;150:3153–61.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Casillas-Ramirez A, Alfany-Fernandez I, Massip-Salcedo M, Juan ME, Planas JM, Serafin A, et al. Retinol-binding protein 4 and peroxisome proliferatior-activated receptor-γin steatotic liver transplantation. J Parmacol Exp Ther. 2011;338:143–53.Google Scholar
  47. 47.
    Jimenez-Castro MB, Elias-Miro M, Mendes-Braz M, Lemoine A, Rimola A, Rodes J, et al. Tauroursodeoxycholic acid affects PPARγ and TLR4 in steatotic liver transplantation. Am J Transpl. 2012;12:3257–71.Google Scholar
  48. 48.
    Alfany-Fernandez I, Casillas-Ramirez A, Bintanel-Morcillo M, Brosnihan KB, Ferrario CM, Serafin A, et al. Therapeutic targets in liver transplantation: angiotensin II in nonsteatotic grafts and angiotensin-(1–7) in steatotic grafts. Am J Transplt. 2009;9:439–51.Google Scholar
  49. 49.
    Ellett JD, Evans ZP, Atkinson C, Schmidt MG, Schnellmann RG, Chavin KD. Toll-like receptor 4 is a key mediator of murine steatotic liver warm ischemia/reperfusion injury. Liver Transpl. 2009;15:1101–9.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Firorini RN, Shafizadeh SF, Polito C, Rodwell DW, Cheng G, Evans Z, et al. Anti-endotoxin monoclonal antibodies are protective against hepatic ischemia/reperfusion injury in steatotic mice. Am J Transpl. 2004;4:1567–73.Google Scholar
  51. 51.
    Zaouali MA, Bardag-Gorce FB, Carbonell T, Oliva J, Pantazi E, Bejaoui M, et al. Proteasome inhibitors protect the steatotic and non-steatotic liver graft against cold ischemia reperfusion injury. Exp Mol Path. 2013;94:352–9.Google Scholar
  52. 52.
    He S, Atkinson C, Evans Z, Ellett JD, Southwood M, Elvington A, et al. A role for compliment in the enhanced susceptibility of steatotic livers to ischemia and reperfusion injury. J Immunol. 2009;183:4764–72.PubMedGoogle Scholar
  53. 53.
    Selzner N, Selzner M, Jochum W, Clavian PA. Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism. J Hepatology. 2003;39:55–61.Google Scholar
  54. 54.
    Rolo AP, Teodoro JS, Peralta C, Rosello-catafau JR, Palmeira CM. Prevention of I/R injury in fatty livers by ischemic preconditioning is associated with increased mitochondrial tolerance: the key role of ATP synthase and mitochondrial permeability transition. Transpl Int. 2009;22:1081–90.PubMedGoogle Scholar
  55. 55.
    Serafin A, Rosello-Catafau J, Prats N, Xaus C, Gelpi E, Peralta C. Ischemic preconditioning increases the tolerance of fatty liver to hepatic ischemia–reperfusion injury in the rat. Am J Pathol. 2002;161:587–601.PubMedCentralPubMedGoogle Scholar
  56. 56.
    Yamagami K, Yamamoto Y, Kume M, Kimoto S, Yamamoto H, Ozaki N, et al. Heat shock preconditioning ameliorates liver injury following normothermic ischemia–reperfusion in steatotic rat livers. J Surg Res. 1998;79:47–53.PubMedGoogle Scholar
  57. 57.
    Massip-Salcedo M, Casillas-Ramirez A, Franco-Gou R, Ben Mosban I, Serafin A, et al. Heat shock proteins and mitogen-activated protein kinases in steatotic livers undergoing ischemia–reperfusion: some answers. Am J Pathol. 2006;168:1474–85.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Bouma HR, Ketelaar ME, Yard BA, Pleoeg RJ, Henning RH. AMP-activated protein kinase as a target for preconditioning in transplantation medicine. Transplantation. 2010;90:353–8.PubMedGoogle Scholar
  59. 59.
    Carrasco-Chaumel E, Rosello-Catafau J, Bartrons R, Franco-Gou R, Xaus C, Casillas A, et al. Adenosine monophosphate-activated protein kinase and nitric oxide in rat steatotic liver transplantation. J Hepatol. 2005;43:997–1006.PubMedGoogle Scholar
  60. 60.
    Serafin A, Rosello-Catafau J, Prats N, Gelpi E, Rodes J, Peralta C. Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion. Hepatology. 2004;39:688–98.PubMedGoogle Scholar
  61. 61.
    Tacchini L, Cario G, De Ponti C, Massip M, Rosello-Catafau J, Peralta C. Up regulation of IL-6 by ischemic preconditioning in normal and fatty rat livers: association with reduction of oxidative stress. Free Radic Res. 2006;40:1206–17.PubMedGoogle Scholar
  62. 62.
    Sun Z, Klein AS, Radaeva S, Hong F, EL-Assal O, Pan HN, et al. In vitro interleukin-6 treatment prevents mortality associated with fatty liver transplants in rats. Gastroenterology. 2003;125:202–15.PubMedGoogle Scholar
  63. 63.
    Hong F, Radaeva S, Pan HN, Tian Z, Veech R, Gao B. Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease. Hepatology. 2004;40:933–41.PubMedGoogle Scholar
  64. 64.
    Fernandez L, Carrasco-Chaumel E, Serafin A, Xaus C, Grande L, Rimola A, et al. Is ischemic preconditioning a useful strategy in steatotic liver transplantation? Am J Transpl. 2004;4:888–99.Google Scholar
  65. 65.
    Bessems M, Doorschodt BM, Kolkert JLP, Vetelainen RL, Van Vliet AK, Vreeling H, et al. Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl. 2007;13:497–504.PubMedGoogle Scholar
  66. 66.
    Vairetti M, Ferrigno A, Carlucci F, Tabucchi A, Rizzo V, Boncompagni E, et al. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl. 2009;15:20–9.PubMedGoogle Scholar
  67. 67.
    Jamieson RW, Zilvetti M, Roy D, Hughes D, Morovat A, Coussions CC, et al. Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model. Transplantation. 2011;92:289–95.PubMedGoogle Scholar
  68. 68.
    Minor T, Akbar S, Tolba R, Domobrowski F. Cold preservation of fatty liver grafts: prevent of functional and ultrastructual impairments by venous oxygen persufflation. J Hepatol. 2000;32:105–11.PubMedGoogle Scholar
  69. 69.
    Minor T, Stegemann J, Hirner A, Koetting M. Impaired autophagic clearance after cold preservation of fatty livers correlates with tissue necrosis upon reperfusion and is reversed by hypothermic reconditioning. Liver Transpl. 2009;15:798–805.PubMedGoogle Scholar
  70. 70.
    Koetting M, Luer B, Efferz P, Paul A, Minor T. Optimal time for hypothermic reconditioning of liver grafts by venous systemic oxygen persufflation in a large animal model. Transplantation. 2011;91:42–7.PubMedGoogle Scholar
  71. 71.
    Minor T, Koetting M, Koetting M, Kaiser G, Efferz P, Luer B, et al. Hypothermic reconditioning by gaseous oxygen improves survival after liver transplantation in the pig. Am J Transpl. 2011;11:2627–34.Google Scholar
  72. 72.
    Srinivasan PK, Yagi S, Doorschodt B, Nagai K, Afify M, Uemoto S, et al. Impact of venous systemic oxygen persufflation supplemented with nitric oxide gas on cold-stored, warm ischemia-damaged experimental liver grafts. Liver Transpl. 2012;18:219–25.PubMedGoogle Scholar
  73. 73.
    Nagai K, Yagi S, Afify M, Bleilevens C, Uemoto S, Tolba RH. Impact of venous-systemic oxygen persufflation with nitric oxide gas on steatotic grafts after partial orthotopic liver transplantation in rats. Transplantation. 2013;95:78–84.PubMedGoogle Scholar
  74. 74.
    Seifalian AM, Chidambaram V, Rolles K, Davidson BR. In vivo demonstration of impaired microcirculation in steatotic human liver grafts. Liver Transpl Surg. 1998;4:71–7.PubMedGoogle Scholar
  75. 75.
    Ijaz S, Yang W, Winslet MC, Seifalian AM. Impairment of hepatic microcirculation in fatty liver. Microcirculation. 2003;10:447–56.PubMedGoogle Scholar
  76. 76.
    Yamagami K, Enders G, Schauer RJ, Leiderer R, Hutter J, Yamamoto Y, et al. Heat-schock preconditioning protects fatty livers in genetically obese zucker rats from microvascular perfusion failure after ischemia reperfusion. Transpl Int. 2003;16:554–61.Google Scholar
  77. 77.
    El-Badry AM, Moritz W, Contaldo C, Tian Y, Graf R, Clavien PA. Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acids. Hepatology. 2007;45:855–63.PubMedGoogle Scholar
  78. 78.
    El-Badry AM, Jang JH, Elsherbiny A, Contaldo C, Tian Y, Raptis DA, et al. Chemical composition of hepatic lipids mediates reperfusion injury of the macrosteatotic mouse liver through thromboxane A2. J Hepatol. 2011;55:1291–9.PubMedGoogle Scholar
  79. 79.
    Zhang JX, Bauer M, Clemens MG. Vessel- and target cell-specific actions of endothelin-1 and endothelin-3 in rat liver. Am J Physiol. 1995;269:G269–77.PubMedGoogle Scholar
  80. 80.
    Mizunuma K, Ohdan H, Tashiro H, Fudaba Y, Ito H, Asahara T. Prevention of ischemia–reperfusion-induced hepatic microcirculatory disruption by inhibiting stellate cell contraction using rock inhibitor. Transplantation. 2003;75:579–86.PubMedGoogle Scholar
  81. 81.
    Ikeda F, Terajima H, Shimamura Y, Kondo T, Yamaoka Y. Reduction of hepatic ischemia/reperfusion-induced injury by a specific rock/rho kinase inhibitor y-27632. J Surg Res. 2003;109:155–60.PubMedGoogle Scholar
  82. 82.
    Kuroda S, Tashiro H, Igarashi Y, Tanimoto Y, Nambu J, Oshita A, et al. Rho inhibitor prevents ischemia–reperfusion injury in rat steatotic liver. J Hepatol. 2012;56:146–52.PubMedGoogle Scholar
  83. 83.
    Fondevila C, Shen XD, Duarte S, Busuttil RW, Coito AJ. Cytoprotective effects of acyclic RGD peptide in steatotic liver cold ischemia and reperfusion injury. Am J Transpl. 2009;9:2240–50.Google Scholar
  84. 84.
    Hasegawa T, Ito Y, Wijeweera J, Liu J, Malle E, Farhood A, et al. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia–reperfusion injury in steatotic livers of ob/ob mice. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1385–95.PubMedGoogle Scholar
  85. 85.
    Yamagami K, Hutter J, Yamamoto Y, Schauer RJ, Enders G, Leiderer R, et al. Synergistic effects of brain death and liver steatosis on the hepatic microcirculation. Transplantation. 2005;80:500–5.PubMedGoogle Scholar
  86. 86.
    Wakai T, Shirai Y, Sakata J, Korita PV, Ajioka Y, Tatakeyama K. Surgical outcomes for hepatocellular carcinoma in nonalcoholic fatty liver disease. J Gastrointest Surg. 2011;15:1450–8.PubMedGoogle Scholar
  87. 87.
    Reddy SK, Marsh W, Varley PR, Mock BK, Chopra KB, Geller DA, et al. Underlying steatohepatitis, but not simple hepatic steatosis, increase morbidity after liver resection: case–control study. Hepatology. 2012;56:2221–30.PubMedGoogle Scholar
  88. 88.
    Jamagin WR, Gonen M, Fong Y, DeMatteo R, Ben-Porat L, Little S, et al. Improvement in perioperative outcome after hepatic resection. Ann Surg. 2002;236:397–407.Google Scholar
  89. 89.
    Cho JY, Suh KS, Kwon CH, Yi NJ, Lee KU. Mild hepatic steatosis is not a major risk factor for hepatectomy and regenerative power is not impaired. Surgery. 2006;139:508–15.PubMedGoogle Scholar
  90. 90.
    Nagai S, Fujimoto Y, Kamei H, Nakamura T, Kiuchi T. Mild hepatic marovesicular steatosis may be a risk factor for hyperbilurubinemia in living liver donors following right hepatectomy. Br J Surg. 2009;96:437–44.PubMedGoogle Scholar
  91. 91.
    Behrns K, Tsiotos G, DeSouza NF, Krishna MK, Ludwig F, Nagorney DM. Hepatic steatosis as a potential risk for major hepatic surgery. J Gastrointest Surg. 1998;2:292–8.PubMedGoogle Scholar
  92. 92.
    de Meijer VE, Kalish BT, Puder M, Ijzermans JNM. Systemic review and meta-analysis of a steatosis as a risk factor in major hepatic resection. Br J Surg. 2010;97:1131–339.Google Scholar
  93. 93.
    McCormack L, Dutkowski P, El-Badry AM, Clavien PA. Liver transplantation using fatty livers: always feasible? J Hepatol. 2011;54:1055–62.PubMedGoogle Scholar
  94. 94.
    Doyle MBM, Vachharajani N, Wellen JR, Anderson CD, Lowell JA, Shenoy S, et al. Short-and long-term outcomes after steatotic liver transplantation. Arch Surg. 2010;145:653–60.PubMedGoogle Scholar
  95. 95.
    McCormack L, Petrowsky H, Jochum W, Mullhaupt B, Weber M, Clavien PA. Use of severely steatotic grafts in liver transplantation: a matched case-control study. Ann Surg. 2007;246:940–8.PubMedGoogle Scholar
  96. 96.
    Spitzer AL, Lao OB, Dick AAS, Bakthavatsalam R, Halldorson JB, Yeh MM, et al. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16:874–84.PubMedGoogle Scholar
  97. 97.
    Soejima Y, Shimada M, Suehiro T, Kishikawa K, Yoshimizu T, Hashimoto K, et al. Use of steatotic graft in living-donor liver transplantation. Transplantation. 2003;76:344–8.PubMedGoogle Scholar
  98. 98.
    Hayashi M, Fujii T, Kiuchi T, Uryuhara K, Kasahara M, Takatsuki M, et al. Effects of fatty filtration of the graft on the outcome of living-related liver transplantation. Transplant Proc. 1999;31:403.PubMedGoogle Scholar
  99. 99.
    Yoong KF, Gunson BK, Neil DAH, Mirza DF, Mayer AD, Buckels JA, et al. Impact of donor liver microvesicular steatosis on the outcome of liver transplantation. Transpl Proc. 1999;31:550–1.Google Scholar
  100. 100.
    Cho JY, Suh KS, Lee HW, Cho EH, Yang SH, Cho YB, et al. Hepatic steatosis is associated with intrahepatic cholestasis and transient hyperbilirubinemia during regeneration after living donor liver transplantation. Transpl Int. 2006;19:807–13.PubMedGoogle Scholar
  101. 101.
    Oshita A, Tashiro H, Amano H, Kobayashi T, Onoe T, Ide K, et al. Safety and feasibility of diet-treated donors with steatotic livers at the initial consultation for living-donor liver transplantation. Transplantation. 2012;93:1024–30.PubMedGoogle Scholar
  102. 102.
    Nakamuta M, Morizono S, Soejima Y, Yoshizumi T, Aishima S, Takaugi S, et al. Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation. Transplantation. 2005;80:608–12.PubMedGoogle Scholar
  103. 103.
    Clavien PA, Selzner M, Rudiger HA, Graf R, Kadry Z, Rousson V, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003;238:843–52.PubMedCentralPubMedGoogle Scholar
  104. 104.
    Domart MC, Esposti DD, Sebagh M, Olaya N, Harper F, Pierron G, et al. Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy. J Hepatol. 2009;51:881–9.PubMedGoogle Scholar
  105. 105.
    Scatton O, Zalinski Z, Jegou D, Compagnon P, Lesurtel M, Belghiti J, et al. Randomized clinical trial ischaemic preconditioning in major liver resection with intermittent pringle manoeuvre. Br J Surg. 2011;98:1236–43.PubMedGoogle Scholar
  106. 106.
    Beck-Schimmer B, Breitenstein S, Urech S, De Conno E, Wittlinger M, Puhan M, et al. A randomized controlled trial on pharmacological preconditioning in liver surgery using volatile anesthetic. Ann Surg. 2008;248:909–18.PubMedGoogle Scholar
  107. 107.
    Azoulay D, del Gaudio M, Andreani P, Ichai P, Sebag M, Adam R, et al. Effects of 10 minutes of ischemic preconditioning of cadaveric liver on the grafts preservation and function: the ying and the yang. Ann Surg. 2005;242:133–9.PubMedCentralPubMedGoogle Scholar
  108. 108.
    Amador A, Grande L, Marti J, Deulofeu R, Miquel R, Sola A, et al. Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial. Am J Transpl. 2007;7(9):2180–9.Google Scholar
  109. 109.
    Jassem W, Fuggle S, Thompson R, Arno M, Taylor J, Byrne J, et al. Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. Liver Transpl. 2009;15:1750–65.PubMedGoogle Scholar
  110. 110.
    Koneru B, Shareef A, Dikdan G, Desai K, Klein KM, Peng B, et al. The ischemic preconditioning paradox in deceased donor liver transplantation—evidence from a prospective randomized single blind clinical trial. Am J Transpl. 2007;7:2788–96.Google Scholar
  111. 111.
    Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ, et al. Hypothermic machine preservation in human liver transplantation. Am J Transpl. 2009;10:372–81.Google Scholar
  112. 112.
    Henry SD, Nachber E, Tulipan J, Stone J, Bae C, Reznik L, et al. Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation. Am J Transpl. 2012;12:2477–86.Google Scholar
  113. 113.
    Op den Dries S, Karimian N, Sutton ME, Westerkamp AC, Nijsten MWN, Gouw ASH, et al. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers. Am J Transpl. 2013;13:1327–35.Google Scholar
  114. 114.
    Treckmann J, Minor T, Saad S, Ozcelik A, Malago M, Broelsh CE, et al. Retrograde oxygen persuflation preservation of human livers: a pilot study. Liver Transpl. 2008;14:358–64.PubMedGoogle Scholar
  115. 115.
    Minor T, Putter C, Gallinat A, Ose C, Kaiser G, Scherag A, et al. Oxygen persufflation as adunct in liver preservation (OPAL): study protocol for a randomized controlled trial. Trials. 2011;12:234.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Hirotaka Tashiro
    • 1
  • Shintaro Kuroda
    • 1
  • Yoshihiro Mikuriya
    • 1
  • Hideki Ohdan
    • 1
  1. 1.Department of Gastroenterological and Transplant SurgeryHiroshima University HospitalHiroshimaJapan

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