Liver Transplantation for Nonalcoholic Steatohepatitis: The New Epidemic

Objective:To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH). Summary of Background Data:With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited. Methods:We conducted an analysis from our prospective database of 144 adult NASH patients who underwent LT between December 1993 and August 2011. Outcomes and resource utilization were compared with other common indications for LT. Independent predictors of graft and patient survival were identified. Results:The average Model for End-Stage Liver Disease score was 33. The frequency of NASH as the primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the second most common indication for LT at our center behind hepatitis C. NASH patients had significantly longer operative times (402 vs 322 minutes; P < 0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001), and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5-year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable with other diagnoses. Age greater than 55 years, pretransplant intubation, dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor age greater than 55 years, and cold ischemia time greater than 550 minutes were significant independent predictors of survival for all patients, whereas body mass index greater than 35 was a predictor in NASH patients only. Conclusions:We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.

[1]  J. Neuberger,et al.  Renal function in patients undergoing transplantation for nonalcoholic steatohepatitis cirrhosis: Time to reconsider immunosuppression regimens? , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  H. Petrowsky,et al.  Strategies for safer liver surgery and partial liver transplantation. , 2007, The New England journal of medicine.

[3]  U. Neumann,et al.  Validation of cardiovascular risk scores in a liver transplant population , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  P. Thuluvath,et al.  Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States , 2002, Hepatology.

[5]  C. Meyer,et al.  Intraoperative blood losses and transfusion requirements during adult liver transplantation remain difficult to predict , 2001, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[6]  J. Perkins,et al.  Liver transplantation at the extremes of the body mass index , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[7]  R. Porte,et al.  Minimizing Blood Loss in Liver Transplantation: Progress through Research and Evolution of Techniques , 2005, Digestive Surgery.

[8]  M. Hawn,et al.  Impact of Obesity on Resource Utilization for General Surgical Procedures , 2005, Annals of surgery.

[9]  M. Malinchoc,et al.  The Impact of Obesity on Long‐term Outcomes in Liver Transplant Recipients—Results of the NIDDK Liver Transplant Database , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  V. Lohsiriwat,et al.  Impact of Metabolic Syndrome on the Short-Term Outcomes of Colorectal Cancer Surgery , 2010, Diseases of the colon and rectum.

[11]  J. Capella,et al.  Predictors of Prolonged Hospital Stay following Open and Laparoscopic Gastric Bypass for Morbid Obesity: Body Mass Index, Length of Surgery, Sleep Apnea, Asthma and the Metabolic Syndrome , 2004, Obesity surgery.

[12]  J. Hiatt,et al.  Analysis of Long-term Outcomes of 3200 Liver Transplantations Over Two Decades: A Single-Center Experience , 2005, Annals of surgery.

[13]  P. Fontes,et al.  Outcome After Liver Transplantation for NASH Cirrhosis , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  J. Ludwig,et al.  Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. , 1980, Mayo Clinic proceedings.

[15]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2008. , 2010, JAMA.

[16]  M. Manos,et al.  Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease , 2005, Hepatology.

[17]  G. Klintmalm,et al.  Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[18]  E. Lyden,et al.  Outcomes of liver transplantation for cryptogenic cirrhosis: a single-center study of 71 patients. , 2003, Transplantation proceedings.

[19]  J. Gornbein,et al.  Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants. , 2001, Transplantation.

[20]  G. Marchesini,et al.  Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome , 2003, Hepatology.

[21]  R. Wolfe,et al.  Effect of body mass index on the survival benefit of liver transplantation , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[22]  G. Klintmalm,et al.  The impact of operative bleeding on outcome in transplantation of the liver. , 1993, Surgery, gynecology & obstetrics.

[23]  C. González Hernández,et al.  [Cryptogenic cirrhosis?]. , 1999, Anales de medicina interna.

[24]  L. Wong,et al.  Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy. , 2005, Kidney international.

[25]  R. Wiesner,et al.  Resource utilization in liver transplantation: effects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group. , 1999, JAMA.

[26]  J. Lysaght,et al.  Obesity and post‐operative complications in patients undergoing non‐bariatric surgery , 2010, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[27]  R. Fisher,et al.  Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[28]  S. Nasraway,et al.  Pretransplant renal dysfunction predicts poorer outcome in liver transplantation. , 1997, Clinical nephrology.

[29]  R Bethene Ervin,et al.  Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006. , 2009, National health statistics reports.

[30]  Eric B. Edwards,et al.  MELD and PELD: Application of survival models to liver allocation , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[31]  E. Brunt,et al.  Histopathology of nonalcoholic fatty liver disease. , 2010, World journal of gastroenterology.

[32]  A. Sanyal.  NASH: A global health problem , 2011, Hepatology research : the official journal of the Japan Society of Hepatology.

[33]  J. Després,et al.  Metabolic syndrome increases operative mortality in patients undergoing coronary artery bypass grafting surgery. , 2007, Journal of the American College of Cardiology.

[34]  J. Heimbach,et al.  Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. , 2011, Gastroenterology.

[35]  G. Ioannou,et al.  Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States , 2012, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[36]  S. Smallbone,et al.  Outcomes of , 2010 .

[37]  Philipp Dutkowski,et al.  Are There Better Guidelines for Allocation in Liver Transplantation?: A Novel Score Targeting Justice and Utility in the Model for End-Stage Liver Disease Era , 2011, Annals of surgery.

[38]  J. Ahmad,et al.  Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[39]  T. Hyslop,et al.  Impact of obesity on perioperative morbidity and mortality after pancreaticoduodenectomy. , 2009, Journal of the American College of Surgeons.

[40]  R. Fisher,et al.  Incidence of prolonged length of stay after orthotopic liver transplantation and its influence on outcomes , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[41]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.

[42]  N. Chalasani,et al.  Treatment of nonalcoholic fatty liver disease , 2003, Current treatment options in gastroenterology.

[43]  Chunhong Bai,et al.  Long-term follow-up of patients with nonalcoholic fatty liver. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[44]  Sam S. Chang,et al.  Increased body mass index predicts increased blood loss during radical cystectomy. , 2004, The Journal of urology.

[45]  T. Gonwa,et al.  Continued Influence of Preoperative Renal Function on Outcome of Orthotopic Liver Transplant (OLTX) in the US: Where Will MELD Lead Us? , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[46]  L. Wong,et al.  Implications of worse renal dysfunction and medical comorbidities in patients with NASH undergoing liver transplant evaluation: impact on MELD and more , 2011, Clinical transplantation.

[47]  J. Emond,et al.  Survival Outcomes Following Liver Transplantation (SOFT) Score: A Novel Method to Predict Patient Survival Following Liver Transplantation , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[48]  Fernando Costa,et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. , 2006, Current opinion in cardiology.

[49]  S. Feng,et al.  Factors influencing liver transplant length of stay at two large‐volume transplant centers , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[50]  Mauro Salizzoni,et al.  Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. , 2002, Gastroenterology.