Obesity and Liver Disease: The New Era of Liver Transplantation
Authors: Jorge A. Marrero
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. See Article on Page 487 Nonalcoholic fatty liver disease (NAFLD) is a spectrum that ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. NAFLD is now the most common chronic liver disease in many developed countries.1 The latest Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients annual liver transplant report showed that hepatitis C virus (HCV) infection was no longer the most common indication for liver transplant; instead, "other/unknown etiology" became the leading indication, and importantly, the highest number of transplants performed were for other/unknown liver diseases.2 The majority of cases categorized as other/unknown liver disease most likely represented NAFLD. This is an important threshold because we are in transition to a noncommunicable disease era of liver disease, with NAFLD leading the way. Obesity is the most common risk factor for the development of NAFLD. Features of the metabolic syndrome including type 2 diabetes mellitus, dyslipidemia, and hypertension are all highly prevalent in NAFLD. Cardiovascular diseases are the most common cause of death in these patients, with liver‐related mortality being the second most common cause.3 The annual direct costs associated with NAFLD in the United States have been estimated to be about $103 billion and are highest in those between 45 and 65 years of age.4 NAFLD is a metabolic disease with multiple comorbidities and a significant burden, making it a challenge to manage. The optimal management for liver transplant candidates with obesity and NAFLD is undefined. Weight loss strategies are limited due to liver decompensation, and these patients are at risk for developing sarcopenia, frailty, and malnutrition, further complicating their management. Bariatric surgery with sleeve gastrectomy has been performed prior to, during, and after liver transplantation successfully; but the sample sizes have been too small to make broad recommendations.5 Patients with NAFLD had the highest pretransplant mortality rates among adults wait‐listed for liver transplant.2 In the perioperative period, patients with obesity had higher nonoperative biliary complications, wound infection and dehiscence, overall infections, and length of stay.6 Interestingly, the overall and graft survival rates of obese patients (body mass index [BMI] < 40 kg/m2) do not appear to differ from those of lean individuals. Patients with a BMI > 40 kg/m2 had reduced 5‐year graft and patient survival rates,7 and the American Association for the Study of Liver Diseases and the American Society of Transplantation have determined that a BMI > 40 kg/m2 is a relative contraindication to liver transplantation.8 Although survival outcomes appear to be comparable between obese and lean individuals, it is clear that obese patients have higher morbidities. It is in this context of NAFLD as the main indication for liver transplantation and the impact of obesity in the outcomes of liver transplantation that Parikh and colleagues evaluated the temporal trends in the rise of obesity and NAFLD‐related wait‐list additions and made projections for the future burden of NAFLD on the liver transplant wait list in the United States.9 The authors used data from the OPTN database from 2000 to 2014, the continuous National Health and Nutrition Examination Survey from 1999 to 2014, and the Behavioral Risk Factor Surveillance System from 2000 to 2014 in order to determine the historical number of wait‐list additions per year, to obtain estimates of national obesity prevalence per year, to estimate obesity prevalence by year and regional divisions instituted by the United Network of Organ Sharing. The authors found that there was an overall increase of 44.9% in the obese population in the United States between 2000 and 2014. NAFLD‐related additions to the wait list also increased from 391 in 2000 to 1,605 in 2014. Interestingly, the NAFLD‐related transplant wait‐list additions were predicted by the prevalence of obesity 9 years prior. In terms of future projections, the authors estimate that the obese population will increase to over 92 million adults by 2025, and the number of NAFLD‐related wait‐list additions is expected to increase by 55.4% (from 1,354 to 2,104) between 2016 and 2030. The authors conclude that there is an expected marked increase in the demand for liver transplantation for patients with NAFLD in the next decade specifically due to an increase in the obese population in the United States. The study by Parikh and colleagues confirms previous reports. Using the best databases available, this study provides the best population‐based estimates on the prevalence of obesity and additions to the liver transplant wait list. The authors find that there is a 9‐year lag between changes in obesity prevalence translating into NAFLD. It is important to note that a decrease in the complications from HCV infection is not expected until well into the next decade, so the burden of chronic liver disease will continue to rise. The authors use the term "nonalcoholic steatohepatitis" throughout their article, but a preferred term is "NAFLD" because of the absence of histopathology in the databases studied. Overall, it is a well‐executed study that shows sobering data on the future disease burden. The increase in obesity and NAFLD‐related wait‐list additions portends a radical change in the way hepatology is practiced moving forward. First, hepatologists will need to assume a significant role in addressing the obesity epidemic, as they did for the hepatotrophic viruses, and participate in public health efforts to curb this issue including in pediatric patients. Second, therapeutic efforts to prevent the progression of NAFLD are inconsistent across medical centers. Because this is a metabolic disease with other medical comorbidities, such as diabetes, addressing obesity and NAFLD will require a multidisciplinary, synergistic approach between hepatologists, dieticians, endocrinologists, psychologists, endoscopists, and surgeons to work together on preventive and therapeutic interventions, as shown in Fig. 1. These services are present in most medical centers in their own silos, and I propose that hepatologists, who already have experience working with other disciplines, should take the lead in marshaling together the multidisciplinary obesity team. Importantly, hepatologists (and other members of the multidisciplinary obesity team) should undergo training by health lifestyle practitioners in order to develop expertise in healthy lifestyle interventions for obese patients, proven to be effective for maintaining long‐term results.10 The care of patients with NAFLD would benefit from a specialized team‐based management of chronic disease strategy, which is being used in cirrhosis with demonstrated advances in quality, cost, use, and outcomes. As health care moves toward value‐based compensation and controlling health care costs is critical, there is urgency in developing this multidisciplinary approach to obesity and in turn NAFLD. Third, the increase in wait‐list additions due to obesity with or without NAFLD has the potential to add significant financial strain to liver transplant programs. The perioperative complications of obese patients will require significant innovations in the care of these patients including treatment while waiting for transplantation (i.e., endoscopic and/or pharmacologic approaches to obesity), transferring perioperative care to the outpatient setting (including aggressive wound care), and aggressive posttransplant interventions by the multidisciplinary obesity team to achieve the best long‐term outcomes.Figure 1: The multidisciplinary obesity team.In this transitional era to increased noncommunicable liver diseases in the United States, the role of the hepatologist will include not only directly treating specific liver diseases and their complications but also serving as part of multidisciplinary teams treating obesity.