Fatty Liver in Liver Transplantation and Surgery

 

 Buy Article Permissions and Reprints

ABSTRACT

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (>60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (<30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.

REFERENCES

• 1 Hilden M, Christoffersen P, Juhl E. Liver histology in a normal population-examinations of 503 consecutive fatal traffic casualties.  Scand J Gastroenterol . 1977;  12 593-597
  PubMedGoogle Scholar
• 2 Underwood G. Prevalence of fatty liver in healthy male adults accidentally killed.  Aviat Space Environ Med . 1984;  55 59-63
  PubMedGoogle Scholar
• 3 Hornboll P, Olsen T. Fatty changes in the liver: the relation to age, overweight and diabetes mellitus.  Acta Pathol Microbiol Immunol Scand . 1982;  90 199-205
  PubMedGoogle Scholar
• 4 D'Alessandro A, Kalayoglu M, Sollinger H. The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation.  Transplantation . 1991;  51 157-163
  PubMedGoogle Scholar
• 5 Miki C, Iriyama K, Mirza D. Postperfusion energy metabolism of steatotic graft and its relation to early graft viability following liver transplantation.  Dig Dis Sci . 1998;  43 74-79
  CrossrefPubMedGoogle Scholar
• 6 Clavien P A, Harvey P R, Strasberg S M. Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies.  Transplantation . 1992;  53 957-978
  PubMedGoogle Scholar
• 7 Portmann B, Wight D. Pathology of liver transplantation. In: Calne R (ed) Liver Transplantation. Orlando, FL: Grune & Stratton, 1987: 437
  Google Scholar
• 8 Bengmark S. Liver steatosis in liver resection.  Digestion . 1969;  2 304-311
  PubMedGoogle Scholar
• 9 Selzner M, Clavien P-A. Resection of liver tumors: special emphasis on neoadjuvant and adjuvant therapy. In: Clavien P-A (ed). Malignant Liver Tumors-Current and Emerging Therapies Malden, MA: Blackwell Science, 1999: 137-149
  Google Scholar
• 10 Adam R, Reynes M, Johann M. The outcome of steatotic grafts in liver transplantation.  Transplant Proc . 1991;  23 1538-1540
  PubMedGoogle Scholar
• 11 Fromenty B, Pessayre D. Impaired mitochondrial function in microvesicular steatosis.  J Hepatol . 1997;  26 43-53
  PubMedGoogle Scholar
• 12 Fromenty B, Berson A, Pessayre D. Microvesicular steatosis and steatohepatitis: role of mitochondrial dysfunction and lipid peroxidation.  J Hepatol . 1997;  26 13-22
  PubMedGoogle Scholar
• 13 Yoong K, Gunson B, Neil D. Impact of donor liver microvesicular steatosis on the outcome of liver retransplantation.  Transplant Proc . 1999;  31 550-551
  CrossrefPubMedGoogle Scholar
• 14 Urena M, Ruiz-Delgado F, Gonzales E. Assessing risk of the use of livers with macro and microsteatosis in a liver transplant program.  Transplant Proc . 1998;  30 3288-3291
  CrossrefPubMedGoogle Scholar
• 15 Fishbein T, Fiel M, Emre S. Use of livers with microvesicular fat safely expands the donor pool.  Transplantation . 1997;  64 248-251
  PubMedGoogle Scholar
• 16 Urena M, Ruiz-Delgado F, Gonzales E. Hepatic steatosis in liver transplant donors: common feature of donor population?.  World J Surg . 1998;  22 837-844
  CrossrefPubMedGoogle Scholar
• 17 Ounwater E, Blasbalg R, Siegelman E. Detection of lipid in abdominal tissue with opposed-phase gradient-echo images at 1.5T: techniques and diagnostic importance.  Radiographics . 1998;  18 1465-1480
  PubMedGoogle Scholar
• 18 Ricci C, Longo R, Gioulis E. Noninvasive in vivo quantitative assessment of fat content in human liver.  J Hepatol . 1997;  27 108-113
  CrossrefPubMedGoogle Scholar
• 19 Ploeg R, D'Allessandro A, Knechtle S. Risk factors for primary dysfunction after liver transplantation-a multivariate analysis.  Transplantation . 1993;  55 807-813
  PubMedGoogle Scholar
• 20 Strasberg S, Howard T, Molmenti E. Selecting the donor liver: risk factors for poor function after orthotopic liver transplantation.  Hepatology . 1994;  20 829-838
  CrossrefPubMedGoogle Scholar
• 21 Canelo R, Braun F, Sattler B. Is a fatty liver dangerous for transplantation?.  Transplant Proc . 1999;  31 414-415
  CrossrefPubMedGoogle Scholar
• 22 Hayashi M, Fujii K, Kiuchi T. Effects of fatty infiltration of the graft on the outcome of living-related liver transplantation.  Transplant Proc . 1999;  31 403
  CrossrefPubMedGoogle Scholar
• 23 Markin R S, Wisecarver J L, Radio S J. Frozen section evaluation of donor livers before transplantation.  Transplantation . 1993;  56 1403-1409
  PubMedGoogle Scholar
• 24 Chui A, Haghighi K, Painter D. Donor fatty (steatotic) liver allografts in orthotopic liver transplantation.  Transplant Proc . 1998;  30 3286-3287
  CrossrefPubMedGoogle Scholar
• 25 Belghiti J, Hiramatsu K, Benoist S. Seven hundred forty-seven hepatectomies in the 1990's: an update to evaluate the actual risk of liver resection.  J Am Coll Surg . 2000;  191 38-46
  CrossrefPubMedGoogle Scholar
• 26 Fong Y, Cohen A, Fortner J. Liver resection for colorectal metastases.  J Clin Oncol . 1997;  15 938-946
  CrossrefPubMedGoogle Scholar
• 27 Behrns K E, Tsiotos G G, DeSouza N F. Hepatic steatosis as a potential risk factor for major hepatic resection.  J Gastrointest Surg . 1998;  2 292-298
  CrossrefPubMedGoogle Scholar
• 28 Teramoto K, Bowers J, Kruskal J. Hepatic microcirculatory changes after reperfusion in fatty and normal liver transplantation in the rat.  Transplantation . 1993;  56 1076-1082
  CrossrefPubMedGoogle Scholar
• 29 Teramoto K, Bowers J, Kruskal J. In vivo microscopic observation of fatty liver grafts after reperfusion.  Transplant Proc . 1994;  26 2391
  PubMedGoogle Scholar
• 30 Ohara K. [Study of microcirculatory changes in experimental dietary fatty liver].  Hokkaido Igaku Zasshi (Hokkaido J Med Sc) . 1989;  64(2) 177-185
  PubMedGoogle Scholar
• 31 Wada K, Fujimoto K, Fujikawa Y. Sinusoidal stenosis as the cause of portal hypertension in choline deficient diet induced fatty cirrhosis of the rat liver.  Acta Path Jpn . 1974;  24 207-217
  PubMedGoogle Scholar
• 32 Hakamada K, Sasaki M, Takahashi K. Sinusoidal flow block after warm ischemia in rats with diet-induced fatty liver.  J Surg Res . 1997;  70 12-20
  CrossrefPubMedGoogle Scholar
• 33 Sindram D, Porte R, Hoffman M. Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver.  Gastroenterology . 2000;  118 183-191
  CrossrefPubMedGoogle Scholar
• 34 Yadav S, Howell D, Steeber D. P-selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver.  Hepatology . 1999;  29 1494-1502
  CrossrefPubMedGoogle Scholar
• 35 Seifalian A, Piasecki C, Agarwal A. The effect of graded steatosis on flow in the hepatic parenchymal microcirculation.  Transplantation . 1999;  68 780-784
  PubMedGoogle Scholar
• 36 Berson A, De Beco V, Letteron P. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes.  Gastroenterology . 1998;  114 764-774
  PubMedGoogle Scholar
• 37 Letteron P, Fromenty B, Terris B. Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice.  J Hepatol . 1996;  24 200-208
  CrossrefPubMedGoogle Scholar
• 38 Fukumori T, Ohkohchi N, Tsukamoto S, Satomi S. Why is fatty liver unsuitable for transplantation?.  <~>Disorientation of mitochondrial ATP synthesis and sinusoidal structure during cold preservation of a liver with steatosis. Transplant Proc . 1997;  29 412-415
  PubMedGoogle Scholar
• 39 Nakano H, Nagasaki H, Barama A. The effect of N-acetylcysteine and anti-intracellular adhesion molecule-I monoclonal antibody against ischemia-reperfusion injury of the steatotic liver produced by a choline-methionine- deficient diet.  Hepatology . 1997;  26 670-678
  PubMedGoogle Scholar
• 40 Zhong Z, Connor H, Stachlewitz R. Role of free radicals in primary nonfunction of marginal fatty grafts from rats treated acutely with ethanol.  Mol Pharmacol . 1997;  52 912-919
  PubMedGoogle Scholar
• 41 Kohli V, Selzner M, Madden J F. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.  Transplantation . 1999;  67 1099-105
  CrossrefPubMedGoogle Scholar
• 42 Gao W, Bentley R C, Madden J F. Apoptosis of sinusoidal endothelial cells is a critical mechanism of prevention injury in rat liver transplantation.  Hepatology . 1998;  27 1652-1660
  CrossrefPubMedGoogle Scholar
• 43 Natori S, Selzner M, Valentino K. Apoptosis of sinusoidal endothelial cells occurs during liver preservation injury by a caspase-dependent mechanism.  Transplantation . 1999;  68 89-96
  PubMedGoogle Scholar
• 44 Kohli V, Madden J F, Bentley R C. Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.  Gastroenterology . 1999;  116 168-178
  PubMedGoogle Scholar
• 45 Cursio R, Gugenheim J, Ricci J E. A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis.  FASEB J . 1999;  13 253-261
  PubMedGoogle Scholar
• 46 Selzner M, Rüdiger H, Sindram D. Mechanisms of ischemic injury are different in the steatotic and normal rat liver.  Hepatology . 2000;  32 1280-1288
  CrossrefPubMedGoogle Scholar
• 47 Marcos A. Right lobe living donor liver transplantation: a review.  Liver Transplant . 2000;  6 3-20
  PubMedGoogle Scholar
• 48 Habenal M, Bilgin N, Karakayah H. Long-term follow-up of living related partial liver donors.  Transplant Proc . 1998;  30 708-709
  CrossrefPubMedGoogle Scholar
• 49 Selzner M, Clavien P A. Failure of regeneration of the steatotic rat liver-disruption at two different levels of the regeneration pathway.  Hepatology . 2000;  31 35-42
  CrossrefPubMedGoogle Scholar
• 50 Clavien P A, Yadav S S, Sindram D, Bentley R C. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans.  Ann Surg . 2000;  232 155-162
  CrossrefPubMedGoogle Scholar
• 51 Belghiti J, Noun R, Malafosse R. Continuous versus intermittent portal triad clamping for liver resection: a controlled study.  Ann Surg . 1999;  229 369-375
  CrossrefPubMedGoogle Scholar
• 52 Rüdiger H, Kang K, Clavien P A. Ischemic preconditioning of the liver is a novel protective strategy, which is comparable to intermittent inflow occlusion for ischemic periods up to 75 minutes (Abstract).  AASLD. 2000; 
  PubMedGoogle Scholar
• 53 Camargo Jr A C, Madden J F, Gao W. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent.  Hepatology . 1997;  26 1513-1520
  PubMedGoogle Scholar
• 54 Cressman D E, Greenbaum L E, DeAngelis R A. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice.  Science . 1996;  274 1379-1383
  CrossrefPubMedGoogle Scholar
• 55 Selzner M, Camargo C, Clavien P A. Ischemia impairs liver regeneration following major tissue loss in the rodent.  Hepatology . 1999;  30 469-475
  CrossrefPubMedGoogle Scholar