The obesity pandemic is an inescapable problem in health care. A recent survey found nearly 80 million Americans, or 36% of the population older than 20 years, to be obese.[1] Those caring for persons with end-stage liver disease have seen a 5.4% increase in the number of liver transplant candidates with a body mass index greater than 30 kg/m2 in the United States.[2] This concern is reflected in the frequency of publications on this topic, including the work in this issue of Liver Transplantation by Perez Protto et al.,[3] who report equivalent results in a matched retrospective analysis of lean and morbidly obese patients undergoing liver transplantation at a single center and cite excellent outcomes for both groups. However, a large retrospective review of liver transplantation in obese patients from the United Kingdom pointed to higher degrees of morbidity and health care resource utilization in patients who were obese versus a leaner cohort.[4] Inferior graft survival and more postoperative complications have also been cited in a number of other studies.[5-8] Although a high body mass index has been found by some to be an independent predictor of mortality after transplantation,[9] others have demonstrated a survival benefit for obese patients.[10, 11] The issue of superior outcomes versus a survival benefit has resulted in a debate over the rationing of the precious resource of donor organs, with some, including the American Association for the Study of Liver Diseases through its published guidelines, advocating restrictions on the transplantation of obese patients.[12, 13] The superb clinical results described by Perez Protto et al. in this issue of Liver Transplantation are in contrast to the various conclusions of other single-center studies contributing to this unsettled issue[14-18] and thus invite a more critical examination of transplantation for the obese patient.

There is little doubt that obesity poses some risk to health, mostly through its association with cardiovascular disease, type 2 diabetes, osteoarthritis, and some cancers. A number of studies have reported U- or J-shaped correlations of obesity with overall mortality.[19, 20] Although one might postulate that obesity is universally associated with higher morbidity and mortality rates, this is not always the case. Findings in critically ill intensive care patients have revealed a somewhat unexpected protective association with survival, although the basis for this has yet to be defined.[21-24] In fact, many of these studies have shown higher mortality rates for underweight patients. The average American can expect to undergo 7 surgical procedures throughout his or her life[25]; as a result, surgery is being scrutinized with the goal of improving results. The National Surgical Quality Improvement Program of the American College of Surgeons provides a robust reporting system designed to produce risk-adjusted outcome measures for national surgical quality improvement.[26, 27] Studies using National Surgical Quality Improvement Program data have failed to find a direct correlation between obesity and mortality in surgical patients.[28-30] The term obesity paradox is used to describe the unexpected protective effect associated with an increased body mass index.[30] Similarly, retrospective analyses of single-center data sets have found no correlation of obesity with overall complications for general or colorectal cases.[31, 32]

In a retrospective study of renal transplant recipients, Lynch et al.[33] linked surgical site infections to premature graft loss, and although obese patients (body mass index > 30 kg/m2) had a higher rate of surgical site infections, obesity itself was not independently associated with worse outcomes in a multivariate analysis. Findings of increased wound complications (eg, infections, hernias, and dehiscence) in obese patients are pervasive across surgical specialties,[34-38] including solid organ transplantation.[39] In a retrospective review of liver transplants, Schaeffer et al.[40] also found that obesity did not affect survival, but it was associated with wound infections. Thus, it appears that although obese patients may have higher rates of wound complications, their survival with respect to surgery and critical illness is no worse.

The concern with obesity in the general population is related primarily to abdominal obesity and its association with cardiometabolic risk and metabolic syndrome.[41] The cluster of variables for metabolic syndrome include visceral obesity, systemic hypertension, dyslipidemia, and insulin resistance. Obesity is independently associated with cerebrovascular disease,[42, 43] coronary heart disease,[44-46] and an increase in overall mortality from cardiovascular complications.[47-49] Are there risks attributable to obesity that are independent of cardiovascular complications? Studies in patients undergoing surgery for coronary heart disease provide a surrogate answer to this question because cardiovascular risk factors are prevalent in both obese and normal-weight subjects. Although the findings are not universal, the majority of these studies have revealed that with the notable exception of a heightened rate of sternal wound infections, there is no increase in morbidity or mortality for the obese patient. Here again, underweight patients appear to be at the greatest risk for adverse outcomes.[50-53] Underweight patients also fare poorly in studies of dialysis and renal transplant patients.[54, 55]

Although excess fat is linked to mortality primarily through cardiovascular risks, the important question is which individuals in this population are in jeopardy. Epidemiological studies have found that 10% to 40% of obese individuals are metabolically healthy with higher insulin sensitivity, an absence of hypertension, and favorable lipid, inflammation, hormone, and liver enzyme profiles.[56] Conversely, there are normal-weight individuals who behave with a phenotypically obese metabolic profile, including insulin resistance, an increased risk for diabetes, hypertriglyceridemia, and atherosclerosis.[57] The difficulty in identifying risk is primarily related to 2 issues: (1) the lack of a consensus on the optimal definition of corpulence and (2) the lack of a mechanistic understanding of how obesity causes an increase in cardiovascular risk. The anthropometric use of the body mass index is convenient and reproducible but does not distinguish fat from the fat-free contributions of muscle and bone to body mass.[58-61] Obesity also exhibits a spectrum of fat distribution with visceral and subcutaneous adipose tissue. Although excess in either compartment can lead to insulin resistance, their structure, composition, metabolic activity, and functional significance differ with varying adipokine profiles. Visceral adipose tissue tends to be associated with a more adverse metabolic, dyslipidemic, and atherogenic phenotype, but the relationship between obesity and cardiometabolic disorders is more complex. Consequently, the pathophysiology associated with excess fat is not purely a matter of size or even distribution but stems from other parameters related to genetics[62-64] and environmental factors shaping the gut microbiome[65, 66] (ie, the populations of bacteria colonizing the gut that are responsible for energy harvesting), which differs in obese and lean individuals. Undoubtedly, better predictors of cardiovascular risk will be developed that supersede the current inaccurate anthropometric descriptions. These will likely incorporate variables of the fat phenotype and distribution as well as genetic and environmental influences.

Obesity is also associated with the explosive growth of nonalcoholic steatohepatitis, which, in turn, is linked to metabolic syndrome, although the causal mechanisms of this relation are not well understood. Nonalcoholic steatohepatitis is the fastest growing indication for liver transplantation in the United States, and this is a trend that shows no signs of slowing.[67] It is predicted that by 2025, nearly 25 million Americans will develop nonalcoholic steatohepatitis, a fifth of whom could undergo transplantation.[68] Furthermore, nonalcoholic steatohepatitis as an etiology of cirrhosis and as an indication for transplantation will accelerate over time because of increasing rates of childhood obesity. Outcomes for patients undergoing liver transplantation for nonalcoholic steatohepatitis have been comparable to outcomes for patients with other indications.[69-71] However, a large series looking at transplantation in patients with nonalcoholic steatohepatitis recently reported longer operative times, more intraoperative blood loss, and longer lengths of stay after transplantation.[68] The nonalcoholic steatohepatitis group had a significantly increased proportion of obese and morbidly obese patients (nearly 50%) in comparison with patients with other etiologies of liver disease. Although the outcomes were similar, the authors concluded that this growing group of patients stresses health care resources significantly.

Because cardiovascular disease significantly threatens operative success, transplant candidates are highly scrutinized and carefully selected to avoid these major sources of short-term morbidity and mortality. Thus, it is no surprise that obese liver transplant recipients have good short-term outcomes, just as the authors of the current study have confirmed.[3] The longer term risks associated with metabolic syndrome or its components affect overall long-term survival in the liver recipient population.

The prevalence of metabolic syndrome has been reported to be 44% to 58% in those followed for at least 6 months after liver transplantation[72-74] versus 23% in the general population.[75] Components of metabolic syndrome are exacerbated after transplantation by organ-sustaining immunosuppressive agents (particularly calcineurin inhibitors and corticosteroids).[76] It has been shown that 26% of transplant patients develop new-onset diabetes after transplantation, and this does not even account for those with nondiabetic levels of hyperglycemia.[77] Hypertension is also affected by immunosuppressive agents, particularly calcineurin inhibitors, which increase vasoconstriction systemically and in the kidneys. A greater than 50% increase in the prevalence of high blood pressure is seen after liver transplantation.[76, 78] Weight gain after transplantation is also common.[79, 80] Although steroids are often blamed, it has been shown that the strongest predictor of posttransplant weight gain is a high pretransplant body mass index,[72, 81] and patients manifest excessive weight gain even under steroid-sparing regimens.[82] These factors and a number of others all influence the long-term outcomes of liver transplants. A prospective, long-term follow-up of liver transplant recipients based on the National Institute of Diabetes and Digestive and Kidney Diseases database revealed the top causes of death more than 1 year after liver transplantation to be graft failure, malignancies, cardiovascular complications, and renal failure, all of which can be interrelated with metabolic syndrome.[83]

When nonalcoholic steatohepatitis is the indication for transplantation, posttransplant steatohepatitis and fibrosis are more common,[84] and furthermore, the presence of metabolic syndrome is predictive of nonalcoholic steatohepatitis recurrence.[85] This raises cardiovascular morbidity and death rates.[86] Cardiovascular events are seen with greater frequency in posttransplant patients with metabolic syndrome versus liver transplant recipients without metabolic syndrome.[73, 74] Renal insufficiency, commonly seen after transplantation and often attributed to calcineurin inhibitor toxicity, is also affected by diabetes and hypertension. In a study of renal failure after liver transplantation,[87] renal biopsies revealed dysfunction to be nearly equally attributable to calcineurin inhibitor toxicity and hypertensive changes or diabetic nephropathy. Collectively, hypertension, weight gain, type 2 diabetes, and cardiovascular complications (essentially metabolic syndrome and its individual components) are all more prevalent in obese liver transplant recipients versus lean recipients and significantly worsen under immunosuppressive therapy. This constellation of risk factors associated with obesity raises posttransplant mortality, but at later time points in this highly select patient population.

With the notable exception of wound complications, no significant short-term morbidity or mortality risk factors have been clearly linked to obesity in liver transplant recipients. It must be appreciated that liver transplant candidates are carefully selected to avoid the obesity-related health hazards that would lead to perioperative cardiovascular events. The majority of studies on the obese liver transplant population have queried large databases that lack granularity, or they are retrospective, single-center analyses often covering different eras of transplantation, and this consequently limits the strength of their conclusions. To the question whether obesity poses a risk to liver transplant recipients, the answer is emphatically yes! Obesity affects long-term outcomes because of its interaction with immunosuppression as well as the increased potential for the development of fatty liver. Obese patients derive benefits from surgery in general and, when indicated, from transplantation,[10, 88, 89] but at the same time, they invite more scrutiny by practitioners. Consequently, in comparison with normal-weight individuals, obese patients are more often denied the advantages that these treatments afford.[90] Obesity is an accelerating health concern, but the mechanisms associated with the increased risk (particularly the cardiovascular risk) are poorly understood. The identification of obesity as a hazard has almost exclusively relied on anthropometric definitions and established comorbidities such as hypertension and type 2 diabetes. Systems biology, though conceptually promising, has not yielded clinically useful associations that guide therapeutic interventions.

In summary, excellent results following liver transplantation can be obtained for highly select obese patients, as confirmed by the work in this issue of Liver Transplantation. However, obesity will continue to challenge the transplant community because of its impact on the development of liver disease; its stress on resource utilization; and the long-term risks of cardiovascular disease, which are magnified by immunosuppression. Future prospective studies are warranted to gain a better understanding of the complexity, heterogeneity, and impact of obesity, particularly in the liver transplant population.


  1. Top of page
  • 1
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 2012:18.
  • 2
    Kim WR, Stock PG, Smith JM, Heimbach JK, Skeans MA, Edwards EB, et al. OPTN/SRTR 2011 annual data report: liver. Am J Transplant 2013;13(suppl 1):73102.
  • 3
    Perez-Protto SE, Quintini C, Reynolds LF, You J, Cywinski JB, Sessler DI, Miller C. Comparable graft and patient survival in lean and obese liver transplant recipients. Liver Transpl 2013;19:907915.
  • 4
    Hakeem AR, Cockbain AJ, Raza SS, Pollard SG, Toogood GJ, Attia MA, et al. Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom. Liver Transpl 2013;19:551562.
  • 5
    LaMattina JC, Foley DP, Fernandez LA, Pirsch JD, Musat AI, D'Alessandro AM, Mezrich JD. Complications associated with liver transplantation in the obese recipient. Clin Transplant 2012;26:910918.
  • 6
    Nair S, Cohen DB, Cohen MP, Tan H, Maley W, Thuluvath PJ. Postoperative morbidity, mortality, costs, and long-term survival in severely obese patients undergoing orthotopic liver transplantation. Am J Gastroenterol 2001;96:842845.
    Direct Link:
  • 7
    Nair S, Verma S, Thuluvath PJ. Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States. Hepatology 2002;35:105109.
  • 8
    Pruett T. Obesity and the liver transplant recipient. Liver Transpl 2002;8:171173.
  • 9
    Dick AA, Spitzer AL, Seifert CF, Deckert A, Carithers RL Jr, Reyes JD, Perkins JD. Liver transplantation at the extremes of the body mass index. Liver Transpl 2009;15:968977.
  • 10
    Pelletier SJ, Schaubel DE, Wei G, Englesbe MJ, Punch JD, Wolfe RA, et al. Effect of body mass index on the survival benefit of liver transplantation. Liver Transpl 2007;13:16781683.
  • 11
    Rustgi VK, Marino G, Rustgi S, Halpern MT, Johnson LB, Tolleris C, Taddei TH. Impact of body mass index on graft failure and overall survival following liver transplant. Clin Transplant 2004;18:634637.
  • 12
    Murray KF, Carithers RL Jr; for AASLD. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 2005;41:14071432.
  • 13
    Thuluvath PJ. Morbid obesity with one or more other serious comorbidities should be a contraindication for liver transplantation. Liver Transpl 2007;13:16271629.
  • 14
    Braunfeld MY, Chan S, Pregler J, Neelakanta G, Sopher MJ, Busuttil RW, Csete M. Liver transplantation in the morbidly obese. J Clin Anesth 1996;8:585590.
  • 15
    Fujikawa T, Fujita S, Mizuno S, Shenkman E, Vogel B, Lipori P, et al. Clinical and financial impact of obesity on the outcome of liver transplantation. Transplant Proc 2006;38:36123614.
  • 16
    Hade AM, Shine AM, Kennedy NP, McCormick PA. Both under-nutrition and obesity increase morbidity following liver transplantation. Ir Med J 2003;96:140142.
  • 17
    Hillingsø JG, Wettergren A, Hyoudo M, Kirkegaard P. Obesity increases mortality in liver transplantation—the Danish experience. Transpl Int 2005;18:12311235.
  • 18
    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;8:667672.
  • 19
    Allison DB, Zhu SK, Plankey M, Faith MS, Heo M. Differential associations of body mass index and adiposity with all-cause mortality among men in the first and second National Health and Nutrition Examination Surveys (NHANES I and NHANES II) follow-up studies. Int J Obes Relat Metab Disord 2002;26:410416.
  • 20
    Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:10831096.
  • 21
    O'Brien JM Jr, Phillips GS, Ali NA, Lucarelli M, Marsh CB, Lemeshow S. Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury. Crit Care Med 2006;34:738744.
  • 22
    Peake SL, Moran JL, Ghelani DR, Lloyd AJ, Walker MJ. The effect of obesity on 12-month survival following admission to intensive care: a prospective study. Crit Care Med 2006;34:29292939.
  • 23
    Pickkers P, de Keizer N, Dusseljee J, Weerheijm D, van der Hoeven JG, Peek N. Body mass index is associated with hospital mortality in critically ill patients: an observational cohort study. Crit Care Med; doi:10.1097/CCM.0b013e31828a2aa1.
  • 24
    Tremblay A, Bandi V. Impact of body mass index on outcomes following critical care. Chest 2003;123:12021207.
  • 25
    Gawande A. Two hundred years of surgery. N Engl J Med 2012;366:17161723.
  • 26
    Khuri SF, Daley J, Henderson W, Hur K, Demakis J, Aust JB, et al. The Department of Veterans Affairs' NSQIP: the first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the measurement and enhancement of the quality of surgical care. National VA Surgical Quality Improvement Program. Ann Surg 1998;228:491507.
  • 27
    Khuri SF, Henderson WG, Daley J, Jonasson O, Jones RS, Campbell DA Jr, et al.; for Principal Site Investigators of the Patient Safety in Surgery Study. The Patient Safety in Surgery Study: background, study design, and patient populations. J Am Coll Surg 2007;204:10891102.
  • 28
    Al-Refaie WB, Parsons HM, Henderson WG, Jensen EH, Tuttle TM, Rothenberger DA, et al. Body mass index and major cancer surgery outcomes: lack of association or need for alternative measurements of obesity? Ann Surg Oncol 2010;17:22642273.
  • 29
    Davenport DL, Xenos ES, Hosokawa P, Radford J, Henderson WG, Endean ED. The influence of body mass index obesity status on vascular surgery 30-day morbidity and mortality. J Vasc Surg 2009;49:140147.
  • 30
    Mullen JT, Moorman DW, Davenport DL. The obesity paradox: body mass index and outcomes in patients undergoing nonbariatric general surgery. Ann Surg 2009;250:166172.
  • 31
    Benoist S, Panis Y, Alves A, Valleur P. Impact of obesity on surgical outcomes after colorectal resection. Am J Surg 2000;179:275281.
  • 32
    Dindo D, Muller MK, Weber M, Clavien PA. Obesity in general elective surgery. Lancet 2003;361:20322035.
  • 33
    Lynch RJ, Ranney DN, Shijie C, Lee DS, Samala N, Englesbe MJ. Obesity, surgical site infection, and outcome following renal transplantation. Ann Surg 2009;250:10141020.
  • 34
    Greenblatt DY, Rajamanickam V, Mell MW. Predictors of surgical site infection after open lower extremity revascularization. J Vasc Surg 2011;54:433439.
  • 35
    Mullen JT, Davenport DL, Hutter MM, Hosokawa PW, Henderson WG, Khuri SF, Moorman DW. Impact of body mass index on perioperative outcomes in patients undergoing major intra-abdominal cancer surgery. Ann Surg Oncol 2008;15:21642172.
  • 36
    Mustain WC, Davenport DL, Hourigan JS, Vargas HD. Obesity and laparoscopic colectomy: outcomes from the ACS-NSQIP database. Dis Colon Rectum 2012;55:429435.
  • 37
    Sandy-Hodgetts K, Carville K, Leslie GD. Determining risk factors for surgical wound dehiscence: a literature review. Int Wound J; doi:10.1111/iwj.12088.
  • 38
    Veljkovic R, Protic M, Gluhovic A, Potic Z, Milosevic Z, Stojadinovic A. Prospective clinical trial of factors predicting the early development of incisional hernia after midline laparotomy. J Am Coll Surg 2010;210:210219.
  • 39
    Mehrabi A, Fonouni H, Wente M, Sadeghi M, Eisenbach C, Encke J, et al. Wound complications following kidney and liver transplantation. Clin Transplant 2006;20(suppl 17):97110.
  • 40
    Schaeffer DF, Yoshida EM, Buczkowski AK, Chung SW, Steinbrecher UP, Erb SE, Scudamore CH. Surgical morbidity in severely obese liver transplant recipients—a single Canadian centre experience. Ann Hepatol 2009;8:3840.
  • 41
    Cornier MA, Després JP, Davis N, Grossniklaus DA, Klein S, Lamarche B, et al.; for American Heart Association Obesity Committee of the Council on Nutrition; Physical Activity and Metabolism; Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Epidemiology and Prevention; Council on the Kidney in Cardiovascular Disease, and Stroke Counci. Assessing adiposity: a scientific statement from the American Heart Association. Circulation 2011;124:19962019.
  • 42
    Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, Manson JE, Buring JE. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation 2005;111:19921998.
  • 43
    Strazzullo P, D'Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke 2010;41:e418e426.
  • 44
    Gruson E, Montaye M, Kee F, Wagner A, Bingham A, Ruidavets JB, et al. Anthropometric assessment of abdominal obesity and coronary heart disease risk in men: the PRIME study. Heart 2010;96:136140.
  • 45
    Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990;322:882889.
  • 46
    Wilsgaard T, Arnesen E. Body mass index and coronary heart disease risk score: the Tromsø study, 1979 to 2001. Ann Epidemiol 2007;17:100105.
  • 47
    Cui R, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S, et al.; for JACC Study Group. Body mass index and mortality from cardiovascular disease among Japanese men and women: the JACC study. Stroke 2005;36:13771382.
  • 48
    Jonsson S, Hedblad B, Engström G, Nilsson P, Berglund G, Janzon L. Influence of obesity on cardiovascular risk. Twenty-three-year follow-up of 22,025 men from an urban Swedish population. Int J Obes Relat Metab Disord 2002;26:10461053.
  • 49
    Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008;359:21052120.
  • 50
    Alam M, Siddiqui S, Lee VV, Elayda MA, Nambi V, Yang EY, et al. Isolated coronary artery bypass grafting in obese individuals: a propensity matched analysis of outcomes. Circ J 2011;75:13781385.
  • 51
    Bhamidipati CM, LaPar DJ, Mehta GS, Kern JA, Upchurch GR Jr, Kron IL, Ailawadi G. Albumin is a better predictor of outcomes than body mass index following coronary artery bypass grafting. Surgery 2011;150:626634.
  • 52
    Engel AM, McDonough S, Smith JM. Does an obese body mass index affect hospital outcomes after coronary artery bypass graft surgery? Ann Thorac Surg 2009;88:17931800.
  • 53
    Sung SH, Wu TC, Huang CH, Lin SJ, Chen JW. Prognostic impact of body mass index in patients undergoing coronary artery bypass surgery. Heart 2011;97:648654.
  • 54
    Chang SH, Coates PT, McDonald SP. Effects of body mass index at transplant on outcomes of kidney transplantation. Transplantation 2007;84:981987.
  • 55
    Johansen KL, Young B, Kaysen GA, Chertow GM. Association of body size with outcomes among patients beginning dialysis. Am J Clin Nutr 2004;80:324332.
  • 56
    Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie ME, Messier V, et al. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes (Lond) 2011;35:971981.
  • 57
    Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, Blair SN. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J 2013;34:389397.
  • 58
    Kragelund C, Omland T. A farewell to body-mass index? Lancet 2005;366:15891591.
  • 59
    Rothman KJ. BMI-related errors in the measurement of obesity. Int J Obes (Lond) 2008;32(suppl 3):S56S59.
  • 60
    Welborn TA, Dhaliwal SS. Preferred clinical measures of central obesity for predicting mortality. Eur J Clin Nutr 2007;61:13731379.
  • 61
    Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, et al.; for INTERHEART Study Investigators. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 2005;366:16401649.
  • 62
    Blackett PR, Sanghera DK. Genetic determinants of cardiometabolic risk: a proposed model for phenotype association and interaction. J Clin Lipidol 2013;7:6581.
  • 63
    Herrera BM, Lindgren CM. The genetics of obesity. Curr Diab Rep 2010;10:498505.
  • 64
    Lusis AJ, Attie AD, Reue K. Metabolic syndrome: from epidemiology to systems biology. Nat Rev Genet 2008;9:819830.
  • 65
    Cani PD. Gut microbiota and obesity: lessons from the microbiome. Brief Funct Genomics; doi:10.1093/bfgp/elt014.
  • 66
    Park DY, Ahn YT, Park SH, Huh CS, Yoo SR, Yu R, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 2013;8:e59470.
  • 67
    Singal AK, Guturu P, Hmoud B, Kuo YF, Salameh H, Wiesner RH. Evolving frequency and outcomes of liver transplantation based on etiology of liver disease. Transplantation 2013;95:755760.
  • 68
    Agopian VG, Kaldas FM, Hong JC, Whittaker M, Holt C, Rana A, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg 2012;256:624633.
  • 69
    Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States. Liver Transpl 2012;18:2937.
  • 70
    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;141:12491253.
  • 71
    Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant 2009;9:782793.
  • 72
    Bianchi G, Marchesini G, Marzocchi R, Pinna AD, Zoli M. Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression. Liver Transpl 2008;14:16481654.
  • 73
    Laish I, Braun M, Mor E, Sulkes J, Harif Y, Ben Ari Z. Metabolic syndrome in liver transplant recipients: prevalence, risk factors, and association with cardiovascular events. Liver Transpl 2011;17:1522.
  • 74
    Laryea M, Watt KD, Molinari M, Walsh MJ, McAlister VC, Marotta PJ, et al. Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events. Liver Transpl 2007;13:11091114.
  • 75
    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;287:356359.
  • 76
    Kallwitz ER. Metabolic syndrome after liver transplantation: preventable illness or common consequence? World J Gastroenterol 2012;18:36273634.
  • 77
    Kuo HT, Sampaio MS, Ye X, Reddy P, Martin P, Bunnapradist S. Risk factors for new-onset diabetes mellitus in adult liver transplant recipients, an analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing database. Transplantation 2010;89:11341140.
  • 78
    Watt KDS. Obesity and metabolic complications of liver transplantation. Liver Transpl 2010;16(suppl 2):S65S71.
  • 79
    Richards J, Gunson B, Johnson J, Neuberger J. Weight gain and obesity after liver transplantation. Transpl Int 2005;18:461466.
  • 80
    Wawrzynowicz-Syczewska M, Karpińska E, Jurczyk K, Laurans L, Boroń-Kaczmarska A. Risk factors and dynamics of weight gain in patients after liver transplantation. Ann Transplant 2009;14:4550.
  • 81
    Anastácio LR, Ferreira LG, de Sena Ribeiro H, Lima AS, Vilela EG, Toulson Davisson Correia MI. Body composition and overweight of liver transplant recipients. Transplantation 2011;92:947951.
  • 82
    Elster EA, Leeser DB, Morrissette C, Pepek JM, Quiko A, Hale DA, et al. Obesity following kidney transplantation and steroid avoidance immunosuppression. Clin Transplant 2008;22:354359.
  • 83
    Watt KD, 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;10:14201427.
  • 84
    Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl 2009;15:18431851.
  • 85
    El Atrache MM, Abouljoud MS, Divine G, Yoshida A, Kim DY, Kazimi MM, et al. Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome. Clin Transplant 2012;26:E505E512.
  • 86
    Bhagat V, Mindikoglu AL, Nudo CG, Schiff ER, Tzakis A, Regev A. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl 2009;15:18141820.
  • 87
    O'Riordan A, Dutt N, Cairns H, Rela M, O'Grady JG, Heaton N, Hendry BM. Renal biopsy in liver transplant recipients. Nephrol Dial Transplant 2009;24:22762282.
  • 88
    Glanton CW, Kao TC, Cruess D, Agodoa LY, Abbott KC. Impact of renal transplantation on survival in end-stage renal disease patients with elevated body mass index. Kidney Int 2003;63:647653.
  • 89
    Pelletier SJ, Maraschio MA, Schaubel DE, Dykstra DM, Punch JD, Wolfe RA, et al. Survival benefit of kidney and liver transplantation for obese patients on the waiting list. Clin Transpl 2003:7788.
  • 90
    Segev DL, Simpkins CE, Thompson RE, Locke JE, Warren DS, Montgomery RA. Obesity impacts access to kidney transplantation. J Am Soc Nephrol 2008;19:349355.