Advertisement

Digestive Diseases and Sciences

, Volume 62, Issue 10, pp 2915–2922 | Cite as

Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes

  • George Cholankeril
  • Robert J. Wong
  • Menghan Hu
  • Ryan B. Perumpail
  • Eric R. Yoo
  • Puneet Puri
  • Zobair M. Younossi
  • Stephen A. Harrison
  • Aijaz AhmedEmail author
Original Article

Abstract

Background and Aims

Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied.

Methods

A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003–2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan–Meier methods and multivariate Cox proportional hazards models.

Results

Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH −77.81%, 95% CI 76.37–79.25 vs. HCV −72.15%, 95% CI 71.37–72.93, P < .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71–0.79, P < .001).

Conclusions

Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.

Keywords

Fatty liver disease Hepatitis C virus Alcoholic liver disease Liver transplantation 

Abbreviations

HCV

Hepatitis C virus

HCC

Hepatocellular carcinoma

LT

Liver transplantation

MELD

Model for end-stage liver disease

UNOS

United Network for Organ Sharing

OPTN

Organ Procurement and Transplantation Network

Notes

Author’s contribution

George Cholankeril, Robert J. Wong, Menghan Hu, and Ryan B. Perumpail helped in study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; and statistical analysis. Eric R. Yoo, Puneet Puri, Zobair M. Younossi, and Stephen A. Harrison contributed to analysis and interpretation of data and critical revision of the manuscript for important intellectual content. Aijaz Ahmed helped in study concept and design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; and study supervision.

Compliance with ethical standards

Conflicts of interest

None of the authors have any conflict of interests related to this publication.

References

  1. 1.
    Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: US, 2011–2014. NCHS Data Brief. 2015;219:1–8.Google Scholar
  2. 2.
    Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–2273.CrossRefPubMedGoogle Scholar
  3. 3.
    Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States. Liver Transpl. 2012;18:29–37.CrossRefPubMedGoogle Scholar
  4. 4.
    Angulo P. Nonalcoholic fatty liver disease and liver transplantation. Liver Transpl. 2006;12:523–534.CrossRefPubMedGoogle Scholar
  5. 5.
    Charlton M, Kasparova P, Weston S, et al. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl. 2001;7:608–614.CrossRefPubMedGoogle Scholar
  6. 6.
    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;141:1249–1253.CrossRefPubMedGoogle Scholar
  7. 7.
    Kemmer N, Neff GW, Franco E, et al. Nonalcoholic fatty liver disease epidemic and its implications for liver transplantation. Transplantation. 2013;96:860–862.PubMedGoogle Scholar
  8. 8.
    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;8:667–672.CrossRefPubMedGoogle Scholar
  9. 9.
    Taniguchi M. Liver transplantation in the MELD era–analysis of the OPTN/UNOS registry. Clin Transpl. 2012:41–65.Google Scholar
  10. 10.
    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;148:547–555.CrossRefPubMedGoogle Scholar
  11. 11.
    Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the US. Hepatology (Baltimore, Md). 2014;59:2188–2195.CrossRefGoogle Scholar
  12. 12.
    National Survey on Drug Use and Health: Detailed Tables [Internet]. 2014. http://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs2014/NSDUH-DetTabs2014.htm-tab7-29b.
  13. 13.
    Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology (Baltimore, Md). 2016;64:73–84.CrossRefGoogle Scholar
  14. 14.
    Das K, Das K, Mukherjee PS, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology (Baltimore, Md). 2010;51:1593–1602.CrossRefGoogle Scholar
  15. 15.
    Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686–690.CrossRefPubMedGoogle Scholar
  16. 16.
    Ekstedt M, Franzen LE, Holmqvist M, et al. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2009;44:366–374.CrossRefPubMedGoogle Scholar
  17. 17.
    Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology (Baltimore, Md). 1999;29:664–669.CrossRefGoogle Scholar
  18. 18.
    Maheshwari A, Thuluvath PJ. Cryptogenic cirrhosis and NAFLD: Are they related? Am J Gastroenterol. 2006;101:664–668.CrossRefPubMedGoogle Scholar
  19. 19.
    Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology (Baltimore, Md). 2000;32:689–692.CrossRefGoogle Scholar
  20. 20.
    Caldwell SH, Lee VD, Kleiner DE, et al. NASH and cryptogenic cirrhosis: a histological analysis. Ann Hepatol. 2009;8:346–352.PubMedGoogle Scholar
  21. 21.
    Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001;7:363–373.CrossRefPubMedGoogle Scholar
  22. 22.
    Maor-Kendler Y, Batts KP, Burgart LJ, et al. Comparative allograft histology after liver transplantation for cryptogenic cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases. Transplantation. 2000;70:292–297.CrossRefPubMedGoogle Scholar
  23. 23.
    Sutedja DS, Gow PJ, Hubscher SG, Elias E. Revealing the cause of cryptogenic cirrhosis by posttransplant liver biopsy. Transplant Proc. 2004;36:2334–2337.CrossRefPubMedGoogle Scholar
  24. 24.
    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;16:431–439.PubMedGoogle Scholar
  25. 25.
    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;95:755–760.CrossRefPubMedGoogle Scholar
  26. 26.
    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;12:394.e1–402.e1.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyUniversity of Tennessee Health Sciences CenterMemphisUSA
  2. 2.Division of Gastroenterology and Hepatology, Alameda Health SystemHighland HospitalOaklandUSA
  3. 3.Department of BiostatisticsBrown University Public School of HealthProvidenceUSA
  4. 4.Division of Gastroenterology and Hepatology, Stanford University Medical CenterStanford University School of MedicinePalo AltoUSA
  5. 5.Department of MedicineUniversity of Illinois College of MedicineChicagoUSA
  6. 6.Division of Gastroenterology, Hepatology and NutritionVirginia Commonwealth UniversityRichmondUSA
  7. 7.Department of Medicine, Center for Liver DiseasesInova Fairfax HospitalFalls ChurchUSA
  8. 8.Betty and Guy Beatty Center for Integrated ResearchInova Health SystemFalls ChurchUSA
  9. 9.Radcliffe Department of MedicineUniversity of OxfordOxfordUK

Personalised recommendations