Surgical Advances in Obese Candidates and Recipients

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1 SUPPLEMENT Surgical Advances in Obese Candidates and Recipients Julie Heimbach Transplant Surgery, Mayo Clinic, Rochester, MN Received August 2, 2016; accepted August 25, The obesity epidemic is having a major impact on liver transplantation (LT). More than one-third of the US population is obese, which has contributed to the rapidly rising incidence of obesity-related liver disease and a steady rise in the number of patients who require LT for nonalcoholic steatohepatitis (NASH). (1) Although only a very small minority of patients with obesityrelated liver disease will progress to decompensated cirrhosis and consideration for LT, the vast number of patients affected is driving the increased demand. (2-4) In fact, NASH has become the second most common indication for listing for LT in the United States, and the third most common indication for transplantation. (5-7) The rising incidence of obesity-related liver disease has also led to a significant impact on the incidence of hepatocellular carcinoma (HCC), which can affect the need for LT. Although the risk of HCC in patients with NASH is lower than in patients with viral hepatitis, the size of the at-risk population is much greater. (8,9) Though outcomes for LT may be similar in wellselected obese versus nonobese patients (Table 1), (10-15) Abbreviations: HCC, hepatocellular carcinoma; ICU, intensive care unit; LOS, length of stay; LT, liver transplantation; NASH, nonalcoholic steatohepatitis; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; SG, sleeve gastrectomy; SRTR, Scientific Registry of Transplant Recipients; UNOS, United Network for Organ Sharing. Address reprint requests to Julie Heimbach, M.D., Transplant Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN Telephone: ; FAX: ; heimbach.julie@mayo.edu Copyright VC 2016 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI /lt Potential conflict of interest: Nothing to report. S62 SUPPLEMENT complication rates for LT in obese patients may be higher (Table 2). (16-21) In addition, obese wait-listed patients have less access to transplantation. (22) Access to available grafts, particularly living donor grafts, will be lower due to graft-to-body-weight restrictions. They may also have less access to the waiting list, though these data aremoredifficulttocapture. (23) Longterm post-lt outcomes may also be affected by obesity-related complications such as recurrent NASH, diabetes, heart disease, and cancer. (24,25) In addition to improving access to LT, weight loss may reduce the risk of recurrent NASH and may also affect other obesity-related complications. However, achieving weight loss is very challenging. A recent study using paired biopsies demonstrated that patients with nonalcoholic fatty liver disease who were successful with achieving >10% total body weight loss either through noninvasive weight loss methods or via bariatric surgery (Fig. 1) had improvement in liver fibrosis. (26) Similar findings on the efficacy of 10% total body weight loss were also reported by Vilar-Gomez et al., (27) though in this report, only 9% of the cohort were able to achieve weight loss. Bariatric surgery may be effective for selected patients in achieving weight loss, though most patients on the LT waiting list have decompensated liver disease and therefore are not candidates for bariatric surgery because of the likelihood of further decompensation of liver disease and subsequent increased risk of perioperative mortality. The risk of 30-day morality in patients with decompensated cirrhosis undergoing bariatric surgery was noted to be 16.7% in a recent report using the nationwide inpatient survey data. (28) Sarcopenia is now an established risk factor for adverse perioperative outcomes, and obese patients may suffer from sarcopenia, despite their excess body weight. (29) Whether intentional medically supervised pretransplant weight loss may exacerbate sarcopenia and portend worse rather than better posttransplant outcomes is not known. Therefore, the

2 LIVER TRANSPLANTATION, Vol. 22, No. S1, 2016 TABLE 1. Summary of Studies on the Impact of Obesity on Patient and Graft Survival Outcomes Following LT BMI Cohorts, Author Era n kg/m 2 Findings Notes Nair et al. (10) (2002) Pelletier et al. (11) (2007) Leonard et al. (12) (2008) Dick et al. (13) (2009) Perez-Protto et al. (14) (2013) Orci et al. (15) (2013) , UNOS data September 2001 to December 2004, UNOS data , NIDDK; , Mayo Clinic , UNOS data 18,172 <25 25,647 wait-list candidates, 4488 transplanted < < ,538 < Decreased patient survival for BMI > 40 kg/m 2 at 30 days and years 1-5 and decreased for BMI > 35 kg/m 2 at 5 years Worse survival for wait-listed candidates with BMI < 20 kg/ m 2 ; no difference for obese candidates or recipients No differences in survival except worse for BMI < 18.5 kg/m 2 Decreased survival for BMI < 18.5 kg/m 2 and for BMI > 40 kg/m 2 Single center 134 >38 versus No differences in patient or graft survival , SRTR 38,194 < No differences in survival for obese and normal weight; BMI < 18.5 kg/m 2 did worse. No difference for those with changes in BMI Earlier era of transplant Looked at both pretransplant and posttransplant survival Ascites was a predictor of post-lt death Small number of patients in extreme groups, relative to total Single center; compared specifically to cohort of normal weight Compared listing BMI to transplant BMI for high and low BMI patients management of obesity before transplant is complex and the limited options that are available must be tailored to the individual patient. Pretransplant Obesity Management Prior to being placed on the waiting list, it is essential that wait-listed patients are carefully screened for obesity-related complications such as coronary artery disease given that the cause of death for most patients with fatty liver disease is actually cardiovascular rather than liver-related. (4) Once listed, patients may have a prolonged wait time, and therefore, careful monitoring of wait-listed patients for the development of cardiac symptoms and continued rescreening is required. In addition to carefully screening for comorbidities associated with obesity, should obese wait-listed patients be asked to lose weight, and if so, how? There are very limited data available to answer this question. However, based on the limited evidence that is available, much of which is indirect, the approach should be tailored to the individual patient considering most importantly the degree of underlying liver disease and their functional status. Well-compensated obese patients who are waiting for LT, such as those with HCC, may be candidates for either noninvasive or invasive pretransplant weight loss. The goal of pretransplant weight loss would be to reduce perioperative complications, increase opportunities for transplantation (such as access to living donor LT), and hopefully reduce longterm complications of obesity. Patients with decompensated liver disease are not candidates for surgical weight loss interventions before transplantation. Severely decompensated or markedly sarcopenic obese patients are also not candidates for noninvasive pretransplant weight loss. If a pretransplant weight loss intervention is attempted, what should it be? A structured noninvasive, multidisciplinary weight loss program involving ongoing dietary education and physical activity may be SUPPLEMENT S63

3 LIVER TRANSPLANTATION, November 2016 TABLE 2. Summary of Studies Related to the Effect of Obesity on Complications Following LT BMI Cohorts, Author Year n kg/m 2 Findings Notes Fujikawa et al. (16) (2006) Nair et al. (17) (2009) Schaeffer et al. (18) (2009) LaMattina et al. (19) (2012) Agopian et al. (20) (2012) Hakeem et al. (21) (2013) , , , Canadian , , , UK center 700 < > < > < < < < >35 No difference in cost, LOS, reoperation, surgical complications for the graft or patient No differences in resource utilization, surgical complications for the graft or patient Increased wound complications, longer LOS Increased operating time, LOS, infection, transfusion, operative complication Increased operative time, hospital stay, and blood loss Longer hospital and ICU stay, increased infection only n 5 37 patients with BMI > 35 kg/m 2 Scoring system combining diabetes, obesity, and prior abdominal surgery Small numbers Patient and graft survival outcome similar Patient and graft outcome similar Patient and graft outcomes similar beneficial for selected patients. Efficacy of noninvasive weight loss efforts is low, but the risk is also low and therefore a structured approach aimed at lifestyle modification should be a part of the initial strategy for wait-list management of selected (see above) obese patients. (30) For those who are unsuccessful with noninvasive weight loss, a very small number may be candidates for pretransplant obesity surgery. Though data are extremely limited, the procedure that may be optimal for this population would be laparoscopic sleeve gastrectomy (SG), a restrictive procedure in which endoscopic access to the distal stomach and duodenum is preserved which may be of importance in case the patient develops gastric varices while waiting for LT or requires access to the biliary tree to manage bile leaks or strictures after LT. (31-33) Weight loss with SG is also more gradual and generally lower than the weight loss noted with Roux-en-Y gastric bypass, which is both a restrictive and malabsorptive procedure. Whether other options such as the recently approved intragastric balloon may be of benefit for wait-listed patients remains to be seen. A single case series from India of pretransplant patients who underwent intragastric balloon placement has been published, though the safety of the intragastric balloon in patients with cirrhosis has not been established which will limit access in the United States. Posttransplant Obesity Management Posttransplant weight loss can be anticipated to have similar benefits as for the nontransplant population. In addition to reducing obesity-related risks such as cardiovascular disease and diabetes, there may also be a benefit in reducing the risk of recurrent steatosis in the liver allograft. (34,35) Again, a structured, noninvasive, multidisciplinary weight loss program should be the foundation, though efficacy is limited. If not successful, or for patients with severe obesity, posttransplant bariatric surgery may be considered. On the basis of the very limited number of available reports, SG appears to be a superior option over Roux-en-Y gastric bypass based on a shorter operative time, a reduced rate of complications, as well as benefits such as lack of malabsorption, preserved access to the biliary tree, and more gradual weight loss than can be expected from SG. (36-39) S64 SUPPLEMENT

4 LIVER TRANSPLANTATION, Vol. 22, No. S1, 2016 FIG. 1. A diagram of the bariatric procedure. Perioperative Obesity Management A single series of combined SG and LT has been published from the Mayo Clinic. (30) In this report, obese patients who were unsuccessful with a noninvasive weight loss protocol prior to LT were offered a SG simultaneous with LT. Outcomes between those with noninvasive weight loss versus the SG group were compared, and it was noted that patients with SG1LT had similar perioperative outcomes, but superior weight loss and markedly improved metabolic profiles in the early follow-up period. Complications were uncommon though 1 patient developed a leak from the staple line, which led to a prolonged recovery. In addition, reflux symptoms are common and patients require close monitoring to ensure they are able to maintain adequate nutrition and hydration in the early postoperative period. Longer-term follow-up with larger numbers are needed to determine if this approach can be justified. Summary Obesity-related liver disease has reached epidemic proportions. Research focused on optimal methods of treating and preventing the underlying problem of obesity is paramount. In the meantime, strategies aimed at addressing the consequences of end-stage liver disease in the obese patient may be employed before, during, and after LT, and the optimal approach depends on the clinical condition of the individual patient. SUPPLEMENT S65

5 LIVER TRANSPLANTATION, November 2016 REFERENCES 1) Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, JAMA 2014;311: ) Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10: ) Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al.; for American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterology. The diagnosis and management of non-alcoholic fatty liver disease: practice guidelines by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012;142: ) Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. 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6 LIVER TRANSPLANTATION, Vol. 22, No. S1, ) Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al.; for STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes-3-year outcomes. N Engl J Med 2014;370: ) Patil DT, Yerian LM. Evolution of nonalcoholic fatty liver disease recurrence after liver transplantation. Liver Transpl 2012;18: ) 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: ) Khoraki J, Katz MG, Funk LM, Greenberg JA, Fernandez LA, Campos GM. Feasibility and outcomes of laparoscopic sleeve gastrectomy after solid organ transplantation. Surg Obes Relat Dis 2016;12: ) Lin MY, Tavakol MM, Sarin A, Amirkiai SM, Rogers SJ, Carter JT, Posselt AM. Safety and feasibility of sleeve gastrectomy in morbidly obese patients following liver transplantation. Surg Endosc 2013;27: ) Al-Nowaylati AR, Al-Haddad BJ, Dorman RB, Alsaied OA, Lake JR, Chinnakotla S, et al. Gastric bypass after liver transplantation. Liver Transpl 2013;19: SUPPLEMENT S67

Debate: A Bridge Too Far Liver Transplantation for Nonalcoholic Steatohepatitis Will Overwhelm the Organ Supply

LIVER TRANSPLANTATION 20:S32 S37, 2014 SUPPLEMENT Debate: A Bridge Too Far Liver Transplantation for Nonalcoholic Steatohepatitis Will Overwhelm the Organ Supply Julie Heimbach Liver Transplant Program,