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Liver Transplantation: the Role of Metabolic Syndrome

  • Liver (J Bajaj, Section Editor)
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Opinion statement

The long-term survival in liver transplant recipients (LTRs) is currently at an historical high level stemming from improvement in perioperative care, infection control, and immunosuppression medications. However, compared to the general population, LTRs have decreased survival. Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity are key determinants of long-term mortality in LTRs. The incidence and prevalence of these metabolic comorbidities is considerably higher in LTRs and likely results from a combination of factors including exposure to chronic immunosuppression, weight gain, and recurrence of chronic liver disease after liver transplantation (LT). Although there is currently little guidance in managing these metabolic conditions post-LT, recommendations are often extrapolated from non-transplant cohorts. In the current review, we explore the relationship between metabolic syndrome and its comorbidities in LTRs.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141(4):1249–53. doi:10.1053/j.gastro.2011.06.061.

    Article  PubMed  Google Scholar 

  2. Kim WR, Lake JR, Smith JM, et al. OPTN/SRTR 2013 Annual Data Report: liver. Am J Transplant. 2015;15(Suppl 2):1–28. doi:10.1111/ajt.13197.

    Article  PubMed  Google Scholar 

  3. • Aberg F, Gissler M, Karlsen TH, et al. Differences in long-term survival among liver transplant recipients and the general population: a population-based Nordic study. Hepatology. 2015;61(2):668–77. doi:10.1002/hep.27538. This article describes liver transplant recipients in a large national registry and showed decreased overall survival compared with the general population.

    Article  PubMed  Google Scholar 

  4. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112(17):2735–52.

    Article  PubMed  Google Scholar 

  5. Lemieux I, Pascot A, Couillard C, et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men? Circulation. 2000;102(2):179–84.

    Article  CAS  PubMed  Google Scholar 

  6. Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53(8):2087–94.

    Article  CAS  PubMed  Google Scholar 

  7. Ferrannini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia. 1991;34(6):416–22.

    Article  CAS  PubMed  Google Scholar 

  8. Gustat J, Srinivasan SR, Elkasabany A, Berenson GS. Relation of self-rated measures of physical activity to multiple risk factors of insulin resistance syndrome in young adults: the Bogalusa Heart Study. J Clin Epidemiol. 2002;55(10):997–1006.

    Article  PubMed  Google Scholar 

  9. Expert Panel on Detection, Evaluation. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97.

    Article  Google Scholar 

  10. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–9.

    Article  PubMed  Google Scholar 

  11. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–421.

    Google Scholar 

  12. Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49(4):403–14.

    Article  CAS  PubMed  Google Scholar 

  13. Prati D, Shiffman ML, Diago M, et al. Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C. J Hepatol. 2006;44(4):679–85.

    Article  CAS  PubMed  Google Scholar 

  14. Kim NH, Kim JH, Kim YJ, et al. Clinical and metabolic factors associated with development and regression of nonalcoholic fatty liver disease in nonobese subjects. Liver Int. 2014;34(4):604–11. doi:10.1111/liv.12454.

    Article  CAS  PubMed  Google Scholar 

  15. Marzouk D, Sass J, Bakr I, et al. Metabolic and cardiovascular risk profiles and hepatitis C virus infection in rural egypt. Gut. 2007;56(8):1105–10.

    Article  CAS  PubMed  Google Scholar 

  16. Moucari R, Asselah T, Cazals-Hatem D, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134(2):416–23. doi:10.1053/j.gastro.2007.11.010.

    Article  CAS  PubMed  Google Scholar 

  17. Wang CS, Wang ST, Yao WJ, Chang TT, Chou P. Hepatitis C virus infection and the development of type 2 diabetes in a community-based longitudinal study. Am J Epidemiol. 2007;166(2):196–203.

    Article  PubMed  Google Scholar 

  18. Persico M, Capasso M, Persico E, et al. Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: insulin resistance and response to antiviral therapy. Hepatology. 2007;46(4):1009–15. doi:10.1002/hep.21782.

    Article  CAS  PubMed  Google Scholar 

  19. Dyal HK, Aguilar M, Bhuket T, et al. Concurrent obesity, diabetes, and steatosis increase risk of advanced fibrosis among HCV patients: a systematic review. Dig Dis Sci. 2015;60(9):2813–24. doi:10.1007/s10620-015-3760-3.

    Article  CAS  PubMed  Google Scholar 

  20. Chang ML, Tsou YK, Hu TH, et al. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance. PLoS One. 2014;9(8):e104783. doi:10.1371/journal.pone.0104783.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Younossi ZM, Elsheikh E, Stepanova M, et al. Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. J Viral Hepat. 2015;22(12):977–82. doi:10.1111/jvh.12448.

    Article  CAS  PubMed  Google Scholar 

  22. Meissner EG, Lee YJ, Osinusi A, et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology. 2015;61(3):790–801. doi:10.1002/hep.27424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wong RJ, Kanwal F, Younossi ZM, Ahmed A. Hepatitis C virus infection and coronary artery disease risk: a systematic review of the literature. Dig Dis Sci. 2014;59(7):1586–93. doi:10.1007/s10620-014-3222-3.

    Article  PubMed  Google Scholar 

  24. Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–21.

    Article  PubMed  Google Scholar 

  25. Ekstedt M, Hagstrom H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547–54. doi:10.1002/hep.27368.

    Article  CAS  PubMed  Google Scholar 

  26. Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31. doi:10.1053/j.gastro.2010.09.038.

    Article  PubMed  Google Scholar 

  27. Kwok R, Choi KC, Wong GL, et al. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut. 2016;65(8):1359–68. doi:10.1136/gutjnl-2015-309265.

    Article  PubMed  Google Scholar 

  28. Loomba R, Abraham M, Unalp A, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology. 2012;56(3):943–51. doi:10.1002/hep.25772.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bugianesi E, Zannoni C, Vanni E, Marzocchi R, Marchesini G. Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship? Dig Liver Dis. 2004;36(3):165–73.

    Article  CAS  PubMed  Google Scholar 

  30. Turati F, Talamini R, Pelucchi C, et al. Metabolic syndrome and hepatocellular carcinoma risk. Br J Cancer. 2013;108(1):222–8. doi:10.1038/bjc.2012.492.

    Article  CAS  PubMed  Google Scholar 

  31. Wong GL, Wong VW, Choi PC, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58(1):111–7. doi:10.1136/gut.2008.157735.

    Article  PubMed  Google Scholar 

  32. Siddiqui MS, Fuchs M, Idowu MO, et al. Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile. Clin Gastroenterol Hepatol. 2015;13(5):1000–8.e3. doi:10.1016/j.cgh.2014.10.008.

    Article  CAS  PubMed  Google Scholar 

  33. Peng S, Plank LD, McCall JL, Gillanders LK, McIlroy K, Gane EJ. Body composition, muscle function, and energy expenditure in patients with liver cirrhosis: a comprehensive study. Am J Clin Nutr. 2007;85(5):1257–66.

    CAS  PubMed  Google Scholar 

  34. Moller S, Wiinberg N, Hernriksen JH. Noninvasive 24-hour ambulatory arterial blood pressure monitoring in cirrhosis. Hepatology. 1995;22(1):88–95.

    CAS  PubMed  Google Scholar 

  35. Laryea M, Watt KD, Molinari M, et al. Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events. Liver Transpl. 2007;13(8):1109–14. doi:10.1002/lt.21126.

    Article  PubMed  Google Scholar 

  36. Bianchi G, Marchesini G, Marzocchi R, Pinna AD, Zoli M. Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression. Liver Transpl. 2008;14(11):1648–54. doi:10.1002/lt.21588.

    Article  PubMed  Google Scholar 

  37. Munoz SJ, Deems RO, Moritz MJ, Martin P, Jarrell BE, Maddrey WC. Hyperlipidemia and obesity after orthotopic liver transplantation. Transplant Proc. 1991;23(1 Pt 2):1480–3.

    CAS  PubMed  Google Scholar 

  38. Stegall MD, Everson G, Schroter G, Bilir B, Karrer F, Kam I. Metabolic complications after liver transplantation. Diabetes, hypercholesterolemia, hypertension, and obesity. Transplantation. 1995;60(9):1057–60.

    CAS  PubMed  Google Scholar 

  39. Navasa M, Bustamante J, Marroni C, et al. Diabetes mellitus after liver transplantation: prevalence and predictive factors. J Hepatol. 1996;25(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  40. Hanouneh IA, Feldstein AE, McCullough AJ, et al. The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation. Liver Transpl. 2008;14(9):1287–93. doi:10.1002/lt.21524.

    Article  PubMed  Google Scholar 

  41. Ruiz-Rebollo ML, Sanchez-Antolin G, Garcia-Pajares F, et al. Risk of development of the metabolic syndrome after orthotopic liver transplantation. Transplant Proc. 2010;42(2):663–5. doi:10.1016/j.transproceed.2010.02.018.

    Article  CAS  PubMed  Google Scholar 

  42. • Garcia-Pajares F, Penas-Herrero I, Sanchez-Ocana R, et al. Metabolic syndrome after liver transplantation: five-year prevalence and risk factors. Transplant Proc. 2016;48(9):3010–2. This recent article documented a 38% 5-year prevalence of metabolic syndrome in liver transplant recipients with pre-transplant obesity and diabetes along with 1-year post-transplant obesity as important risk factors.

    Article  CAS  PubMed  Google Scholar 

  43. James PA, Oparil S, Carter BL, et al. Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20. doi:10.1001/jama.2013.284427.

    Article  CAS  PubMed  Google Scholar 

  44. Parekh J, Corley DA, Feng S. Diabetes, hypertension and hyperlipidemia: prevalence over time and impact on long-term survival after liver transplantation. Am J Transplant. 2012;12(8):2181–7. doi:10.1111/j.1600-6143.2012.04077.x.

    Article  CAS  PubMed  Google Scholar 

  45. Albeldawi M, Aggarwal A, Madhwal S, et al. Cumulative risk of cardiovascular events after orthotopic liver transplantation. Liver Transpl. 2012;18(3):370–5. doi:10.1002/lt.22468.

    Article  PubMed  Google Scholar 

  46. Martinez-Saldivar B, Prieto J, Berenguer M, et al. Control of blood pressure in liver transplant recipients. Transplantation. 2012;93(10):1031–7. doi:10.1097/TP.0b013e31824cd5e6.

    Article  PubMed  Google Scholar 

  47. Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Immunosuppression impact on long-term cardiovascular complications after liver transplantation. Am J Surg. 2002;183(5):595–9.

    Article  CAS  PubMed  Google Scholar 

  48. Stegall MD, Everson G, Schroter G, Bilir B, Karrer F, Kam I. Metabolic complications after liver transplantation. Diabetes, hypercholesterolemia, hypertension, and obesity. Transplantation. 1995;60(9):1057–60.

    CAS  PubMed  Google Scholar 

  49. Sheiner PA, Magliocca JF, Bodian CA, et al. Long-term medical complications in patients surviving > or = 5 years after liver transplant. Transplantation. 2000;69(5):781–9.

    Article  CAS  PubMed  Google Scholar 

  50. Hanouneh IA, Feldstein AE, McCullough AJ, et al. The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation. Liver Transpl. 2008;14(9):1287–93. doi:10.1002/lt.21524.

    Article  PubMed  Google Scholar 

  51. Johnston SD, Morris JK, Cramb R, Gunson BK, Neuberger J. Cardiovascular morbidity and mortality after orthotopic liver transplantation. Transplantation. 2002;73(6):901–6.

    Article  PubMed  Google Scholar 

  52. Dopazo C, Bilbao I, Castells LL, et al. Analysis of adult 20-year survivors after liver transplantation. Hepatol Int. 2015;9(3):461–70. doi:10.1007/s12072-014-9577-x.

    Article  CAS  PubMed  Google Scholar 

  53. Adamczak M, Gazda M, Gojowy D, Dudzicz S, Karkoszka H, Wiecek A. 3a.03: hypertension in patients after liver transplantation. J Hypertens. 2015;33(Suppl 1:e32) doi:10.1097/01.hjh.0000467433.18172.d1.

  54. Neal DA, Brown MJ, Wilkinson IB, Alexander GJ. Mechanisms of hypertension after liver transplantation. Transplantation. 2005;79(8):935–40.

    Article  PubMed  Google Scholar 

  55. Saruta T. Mechanism of glucocorticoid-induced hypertension. Hypertens Res. 1996;19(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  56. Ong SL, Whitworth JA. How do glucocorticoids cause hypertension: role of nitric oxide deficiency, oxidative stress, and eicosanoids. Endocrinol Metab Clin N Am 2011;40(2):393–407, ix. doi: 10.1016/j.ecl.2011.01.010.

    Article  CAS  Google Scholar 

  57. Fairfield C, Penninga L, Powell J, Harrison EM, Wigmore SJ. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients. Cochrane Database Syst Rev. 2015;(12):CD007606. doi(12):CD007606. doi: 10.1002/14651858.CD007606.pub3.

  58. Canzanello VJ, Textor SC, Taler SJ, et al. Late hypertension after liver transplantation: a comparison of cyclosporine and tacrolimus (FK 506). Liver Transpl Surg. 1998;4(4):328–34.

    Article  CAS  PubMed  Google Scholar 

  59. Muduma G, Saunders R, Odeyemi I, Pollock RF. Systematic review and meta-analysis of tacrolimus versus ciclosporin as primary immunosuppression after liver transplant. PLoS One. 2016;11(11):e0160421. doi:10.1371/journal.pone.0160421.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hoorn EJ, Walsh SB, McCormick JA, Zietse R, Unwin RJ, Ellison DH. Pathogenesis of calcineurin inhibitor-induced hypertension. J Nephrol. 2012;25(3):269–75. doi:10.5301/jn.5000174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Leithead JA, Ferguson JW, Hayes PC. Modifiable patient factors are associated with the late decline in renal function following liver transplantation. Clin Transpl. 2012;26(3):E316–23. doi:10.1111/j.1399-0012.2012.01650.x.

    Article  Google Scholar 

  62. Howard G, Banach M, Cushman M, et al. Is blood pressure control for stroke prevention the correct goal? The lost opportunity of preventing hypertension. Stroke. 2015;46(6):1595–600. doi:10.1161/STROKEAHA.115.009128.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sciarretta S, Palano F, Tocci G, Baldini R, Volpe M. Antihypertensive treatment and development of heart failure in hypertension: a Bayesian network meta-analysis of studies in patients with hypertension and high cardiovascular risk. Arch Intern Med. 2011;171(5):384–94. doi:10.1001/archinternmed.2010.427.

    PubMed  Google Scholar 

  64. Lentine KL, Costa SP, Weir MR, et al. Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the american heart association and the American College of Cardiology Foundation: endorsed by the American Society of Transplant Surgeons, American Society of Transplantation, and National Kidney Foundation. Circulation. 2012;126(5):617–63.

    Article  PubMed  Google Scholar 

  65. Neal DA, Brown MJ, Wilkinson IB, Byrne CD, Alexander GJ. Hemodynamic effects of amlodipine, bisoprolol, and lisinopril in hypertensive patients after liver transplantation. Transplantation. 2004;77(5):748–50.

    Article  CAS  PubMed  Google Scholar 

  66. Watt KDS, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post liver transplant: results of the NIDDK long term follow-up study. Am J Transplant. 2010;10(6):1420–7. doi:10.1111/j.1600-6143.2010.03126.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Galioto A, Semplicini A, Zanus G, et al. Nifedipine versus carvedilol in the treatment of de novo arterial hypertension after liver transplantation: results of a controlled clinical trial. Liver Transpl. 2008;14(7):1020–8. doi:10.1002/lt.21442.

    Article  PubMed  Google Scholar 

  68. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349(10):931–40. doi:10.1056/NEJMoa021744.

    Article  CAS  PubMed  Google Scholar 

  69. Calvino J, Lens XM, Romero R, Sanchez-Guisande D. Long-term anti-proteinuric effect of losartan in renal transplant recipients treated for hypertension. Nephrol Dial Transplant. 2000;15(1):82–6.

    Article  CAS  PubMed  Google Scholar 

  70. Perez MJ, Garcia DM, Taybi BJ, et al. Cardiovascular risk factors after liver transplantation: analysis of related factors. Transplant Proc. 2011;43(3):739–41. doi:10.1016/j.transproceed.2011.03.004.

    Article  CAS  PubMed  Google Scholar 

  71. Laish I, Braun M, Mor E, Sulkes J, Harif Y, Ben AZ. Metabolic syndrome in liver transplant recipients: prevalence, risk factors, and association with cardiovascular events. Liver Transpl. 2011;17(1):15–22. doi:10.1002/lt.22198.

    Article  PubMed  Google Scholar 

  72. Fernandez-Miranda C, Guijarro C, de la Calle A, et al. Lipid abnormalities in stable liver transplant recipients—effects of cyclosporin, tacrolimus, and steroids. Transpl Int. 1998;11(2):137–42.

    Article  CAS  PubMed  Google Scholar 

  73. Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33(4):289–94.

    Article  CAS  PubMed  Google Scholar 

  74. Wu J, Zhu YH, Patel SB. Cyclosporin-induced dyslipoproteinemia is associated with selective activation of SREBP-2. Am J Phys. 1999;277(6 Pt 1):E1087–94.

    CAS  Google Scholar 

  75. Vaziri ND, Liang K, Azad H. Effect of cyclosporine on HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, HDL receptor, VLDL receptor, and lipoprotein lipase expressions. J Pharmacol Exp Ther. 2000;294(2):778–83.

    CAS  PubMed  Google Scholar 

  76. Hulzebos CV, Bijleveld CM, Stellaard F, et al. Cyclosporine A-induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation. Liver Transpl. 2004;10(7):872–80. doi:10.1002/lt.20168.

    Article  PubMed  Google Scholar 

  77. Manzarbeitia C, Reich DJ, Rothstein KD, Braitman LE, Levin S, Munoz SJ. Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients. Liver Transpl. 2001;7(2):93–9.

    Article  CAS  PubMed  Google Scholar 

  78. Roy A, Kneteman N, Lilly L, et al. Tacrolimus as intervention in the treatment of hyperlipidemia after liver transplant. Transplantation. 2006;82(4):494–500. doi:10.1097/01.tp.0000231711.82193.41.

    Article  CAS  PubMed  Google Scholar 

  79. • Chhatrala R, Siddiqui MB, Stravitz RT, et al. Evolution of serum atherogenic risk in liver transplant recipients: role of lipoproteins and metabolic and inflammatory markers. Liver Transpl. 2015;21(5):623–30. doi:10.1002/lt.24100. This article showed that specific findings of lipid panels in liver transplant recipients are different from controls and linked with immunosuppressive drug levels.

    Article  PubMed  Google Scholar 

  80. Idowu MO, Chhatrala R, Siddiqui MB, et al. De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients. Liver Transpl. 2015;21(11):1395–402. doi:10.1002/lt.24223.

    Article  PubMed  Google Scholar 

  81. Imagawa DK, Dawson S, Holt CD, et al. Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin. Transplantation. 1996;62(7):934–42.

    Article  CAS  PubMed  Google Scholar 

  82. Taylor PJ, Kubler PA, Lynch SV, Allen J, Butler M, Pillans PI. Effect of atorvastatin on cyclosporine pharmacokinetics in liver transplant recipients. Ann Pharmacother. 2004;38(2):205–8. doi:10.1345/aph.1D388.

    Article  CAS  PubMed  Google Scholar 

  83. Jun M, Zhu B, Tonelli M, et al. Effects of fibrates in kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2012;60(20):2061–71. doi:10.1016/j.jacc.2012.07.049.

    Article  CAS  PubMed  Google Scholar 

  84. dos Santos AG, Guardia AC, Pereira TS, et al. Rhabdomyolysis as a clinical manifestation of association with ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-alpha in liver-transplanted patients: a case report and literature review. Transplant Proc. 2014;46(6):1887–8. doi:10.1016/j.transproceed.2014.05.065.

    Article  PubMed  Google Scholar 

  85. Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 2003;41(4 Suppl 3):I–IV.

    Google Scholar 

  86. Almutairi F, Peterson TC, Molinari M, Walsh MJ, Alwayn I, Peltekian KM. Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia. Liver Transpl. 2009;15(5):504–8. doi:10.1002/lt.21710.

    Article  PubMed  Google Scholar 

  87. Weintraub H. Update on marine omega-3 fatty acids: management of dyslipidemia and current omega-3 treatment options. Atherosclerosis. 2013;230(2):381–9. doi:10.1016/j.atherosclerosis.2013.07.041.

    Article  CAS  PubMed  Google Scholar 

  88. Wang X, Li J, Riaz DR, Shi G, Liu C, Dai Y. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12(3):394–402.e1. doi:10.1016/j.cgh.2013.09.023.

    Article  PubMed  Google Scholar 

  89. Leonard J, Heimbach JK, Malinchoc M, Watt K, Charlton M. The impact of obesity on long-term outcomes in liver transplant recipients-results of the NIDDK liver transplant database. Am J Transplant. 2008;8(3):667–72. doi:10.1111/j.1600-6143.2007.02100.x.

    Article  CAS  PubMed  Google Scholar 

  90. Saab S, Lalezari D, Pruthi P, Alper T, Tong MJ. The impact of obesity on patient survival in liver transplant recipients: a meta-analysis. Liver Int. 2015;35(1):164–70. doi:10.1111/liv.12431.

    Article  PubMed  Google Scholar 

  91. • Fussner LA, Heimbach JK, Fan C, et al. Cardiovascular disease after liver transplantation: when, what, and who is at risk. Liver Transpl. 2015;21(7):889–96. doi:10.1002/lt.24137. This article showed that early weight gain after liver transplantation increases the risk of developing metabolic syndrome.

    Article  PubMed  Google Scholar 

  92. Richards J, Gunson B, Johnson J, Neuberger J. Weight gain and obesity after liver transplantation. Transpl Int. 2005;18(4):461–6.

    Article  PubMed  Google Scholar 

  93. Wawrzynowicz-Syczewska M, Karpinska E, Jurczyk K, Laurans L, Boron-Kaczmarska A. Risk factors and dynamics of weight gain in patients after liver transplantation. Ann Transplant. 2009;14(3):45–50.

    PubMed  Google Scholar 

  94. Everhart JE, Lombardero M, Lake JR, Wiesner RH, Zetterman RK, Hoofnagle JH. Weight change and obesity after liver transplantation: incidence and risk factors. Liver Transpl Surg. 1998;4(4):285–96.

    Article  CAS  PubMed  Google Scholar 

  95. Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Immunosuppression impact on long-term cardiovascular complications after liver transplantation. Am J Surg. 2002;183(5):595–9.

    Article  CAS  PubMed  Google Scholar 

  96. Masetti M, Montalti R, Rompianesi G, et al. Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function. Am J Transplant. 2010;10(10):2252–62. doi:10.1111/j.1600-6143.2010.03128.x.

    Article  CAS  PubMed  Google Scholar 

  97. LaMattina JC, Foley DP, Fernandez LA, et al. Complications associated with liver transplantation in the obese recipient. Clin Transpl. 2012;26(6):910–8. doi:10.1111/j.1399-0012.2012.01669.x.

    Article  Google Scholar 

  98. Dick AA, Spitzer AL, Seifert CF, et al. Liver transplantation at the extremes of the body mass index. Liver Transpl. 2009;15(8):968–77. doi:10.1002/lt.21785.

    Article  PubMed  Google Scholar 

  99. Perez-Protto SE, Quintini C, Reynolds LF, et al. Comparable graft and patient survival in lean and obese liver transplant recipients. Liver Transpl. 2013;19(8):907–15. doi:10.1002/lt.23680.

    Article  PubMed  Google Scholar 

  100. Cassiman D, Roelants M, Vandenplas G, et al. Orlistat treatment is safe in overweight and obese liver transplant recipients: a prospective, open label trial. Transpl Int. 2006;19(12):1000–5.

    Article  CAS  PubMed  Google Scholar 

  101. Lucey MR, Terrault N, Ojo L, et al. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013;19(1):3–26. doi:10.1002/lt.23566.

    Article  PubMed  Google Scholar 

  102. Tariciotti L, D'Ugo S, Manzia TM, et al. Combined liver transplantation and sleeve gastrectomy for end-stage liver disease in a bariatric patient: first European case-report. Int J Surg Case Rep. 2016;28:38–41.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Elli EF, Gonzalez-Heredia R, Sanchez-Johnsen L, Patel N, Garcia-Roca R, Oberholzer J. Sleeve gastrectomy surgery in obese patients post-organ transplantation. Surg Obes Relat Dis. 2016;12(3):528–34. doi:10.1016/j.soard.2015.11.030.

    Article  PubMed  Google Scholar 

  104. Honda M, Asonuma K, Hayashida S, et al. Incidence and risk factors for new-onset diabetes in living-donor liver transplant recipients. Clin Transpl. 2013;27(3):426–35. doi:10.1111/ctr.12103.

    Article  Google Scholar 

  105. Lv C, Zhang Y, Chen X, et al. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes. 2015;7(6):881–90. doi:10.1111/1753-0407.12275.

    Article  CAS  PubMed  Google Scholar 

  106. Li DW, Lu TF, Hua XW, et al. Risk factors for new onset diabetes mellitus after liver transplantation: a meta-analysis. World J Gastroenterol. 2015;21(20):6329–40. doi:10.3748/wjg.v21.i20.6329.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Yadav AD, Chang YH, Aqel BA, et al. New onset diabetes mellitus in living donor versus deceased donor liver transplant recipients: analysis of the UNOS/OPTN database. J Transp Secur. 2013;2013:269096. doi:10.1155/2013/269096.

    Google Scholar 

  108. John PR, Thuluvath PJ. Outcome of patients with new-onset diabetes mellitus after liver transplantation compared with those without diabetes mellitus. Liver Transpl. 2002;8(8):708–13.

    Article  PubMed  Google Scholar 

  109. Yoo HY, Thuluvath PJ. The effect of insulin-dependent diabetes mellitus on outcome of liver transplantation. Transplantation. 2002;74(7):1007–12. doi:10.1097/01.TP.0000032436.89407.31.

    Article  CAS  PubMed  Google Scholar 

  110. Moon JI, Barbeito R, Faradji RN, Gaynor JJ, Tzakis AG. Negative impact of new-onset diabetes mellitus on patient and graft survival after liver transplantation: long-term follow up. Transplantation. 2006;82(12):1625–8. doi:10.1097/01.tp.0000250361.60415.96.

    Article  PubMed  Google Scholar 

  111. Stockmann M, Konrad T, Nolting S, et al. Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation. Liver Transpl. 2006;12(4):535–43. doi:10.1002/lt.20633.

    Article  PubMed  Google Scholar 

  112. Perseghin G, Mazzaferro V, Sereni LP, et al. Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: effect of liver transplantation. Hepatology. 2000;31(3):694–703.

    Article  CAS  PubMed  Google Scholar 

  113. Sgourakis G, Dedemadi G. Corticosteroid-free immunosuppression in liver transplantation: an evidence-based review. World J Gastroenterol. 2014;20(31):10703–14. doi:10.3748/wjg.v20.i31.10703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Larsen JL, Bennett RG, Burkman T, et al. Tacrolimus and sirolimus cause insulin resistance in normal sprague dawley rats. Transplantation. 2006;82(4):466–70. doi:10.1097/01.tp.0000229384.22217.15.

    Article  CAS  PubMed  Google Scholar 

  115. Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev. 2006;(4)(4):CD005161. doi: 10.1002/14651858.CD005161.pub2.

  116. Penninga L, Wettergren A, Wilson CH, Chan AW, Steinbruchel DA, Gluud C. Antibody induction versus corticosteroid induction for liver transplant recipients. Cochrane Database Syst Rev. 2014;(5):CD010252. doi(5):CD010252. doi: 10.1002/14651858.CD010252.pub2.

  117. Sgourakis G, Dedemadi G. Corticosteroid-free immunosuppression in liver transplantation: an evidence-based review. World J Gastroenterol. 2014;20(31):10703–14. doi:10.3748/wjg.v20.i31.10703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Weiler N, Thrun I, Hoppe-Lotichius M, Zimmermann T, Kraemer I, Otto G. Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double-blinded trial. Transplantation. 2010;90(12):1562–6. doi:10.1097/TP.0b013e3181ff8794.

    Article  CAS  PubMed  Google Scholar 

  119. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the united states. Gastroenterology. 2015;148(3):547–55. doi:10.1053/j.gastro.2014.11.039.

    Article  PubMed  Google Scholar 

  120. Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001;7(4):363–73.

    Article  CAS  PubMed  Google Scholar 

  121. Yalamanchili K, Saadeh S, Klintmalm GB, Jennings LW, Davis GL. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease. Liver Transpl. 2010;16(4):431–9. doi:10.1002/lt.22004.

    PubMed  Google Scholar 

  122. Dureja P, Mellinger J, Agni R, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011;91(6):684–9. doi:10.1097/TP.0b013e31820b6b84.

    Article  PubMed  Google Scholar 

  123. Finkenstedt A, Auer C, Glodny B, et al. Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clin Gastroenterol Hepatol. 2013;11(12):1667–72. doi:10.1016/j.cgh.2013.06.025.

    Article  CAS  PubMed  Google Scholar 

  124. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121–9. doi:10.1002/hep.23276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–85. doi:10.1056/NEJMoa0907929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956–65. doi:10.1016/S0140-6736(14)61933-4.

    Article  CAS  PubMed  Google Scholar 

  127. Schmilovitz-Weiss H, Laish I, Levi Z, et al. Serum adipocyte fatty acid binding protein in liver transplant recipients and the metabolic syndrome. Ann Hepatol. 2012;11(3):343–9.

    CAS  PubMed  Google Scholar 

  128. Tandon P, Ney M, Irwin I, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012;18(10):1209–16. doi:10.1002/lt.23495.

    Article  PubMed  Google Scholar 

  129. Alvares-da-Silva MR. Reverbel da Silveira T. Comparison between handgrip strength, subjective global assessment, and prognostic nutritional index in assessing malnutrition and predicting clinical outcome in cirrhotic outpatients. Nutrition. 2005;21(2):113–7.

    Article  PubMed  Google Scholar 

  130. Figueiredo FA, Dickson ER, Pasha TM, et al. Utility of standard nutritional parameters in detecting body cell mass depletion in patients with end-stage liver disease. Liver Transpl. 2000;6(5):575–81.

    Article  CAS  PubMed  Google Scholar 

  131. Heimbach JK, Watt KD, Poterucha JJ, et al. Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease. Am J Transplant. 2013;13(2):363–8. doi:10.1111/j.1600-6143.2012.04318.x.

    Article  CAS  PubMed  Google Scholar 

  132. Brunault P, Salame E, Jaafari N, et al. Why do liver transplant patients so often become obese? The addiction transfer hypothesis. Med Hypotheses. 2015;85(1):68–75. doi:10.1016/j.mehy.2015.03.026.

    Article  PubMed  Google Scholar 

  133. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 26;336(7650):924–926. doi: 10.1136/bmj.39489.470347.AD.

  134. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society. Obesity. 2014;2:S5–39. doi:10.1002/oby.20821.

    Google Scholar 

  135. James PA, Oparil S, Carter BL, et al. Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20. doi:10.1001/jama.2013.284427.

    Article  CAS  PubMed  Google Scholar 

  136. American Diabetes Association. Standards of medical care in diabetes-2017: summary of revisions. Diabetes Care. 2017;40(1):S4–5. doi:10.2337/dc17-S003.

    Article  Google Scholar 

  137. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25):2889–934. doi:10.1016/j.jacc.2013.11.002.

    Article  PubMed  Google Scholar 

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    Brian C. Davis MD & M. Shadab Siddiqui MD

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Davis, B.C., Shadab Siddiqui, M. Liver Transplantation: the Role of Metabolic Syndrome. Curr Treat Options Gastro 15, 316–331 (2017). https://doi.org/10.1007/s11938-017-0135-1

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