Abstract
Background
Non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is
a rising indication for liver transplantation. This unique population, with multiple
comorbidities, has potential for worse post-transplant outcomes. We compared post-transplant
survival of NASH and non-NASH HCC patients using a large cohort.
Methods
Adults transplanted for HCC between 2008 and 2018, from United Network for Organ Sharing
(UNOS) and University Health Network (UHN) databases were divided into two populations:
NASH and non-NASH. Recipient characteristics and post-transplant survival were compared.
Subgroup analyses were performed within and beyond Milan criteria.
Results
2071 of 20,672 (10.0%) patients underwent transplantation for NASH HCC, with annual
proportional increase of 1.2%UHN (p = 0.02) and 1.3%UNOS (p < 0.001). The 1-,3-,5-year
post-transplant survival were 90.8%, 83.9%, 76.3% NASH HCC versus 91.9%, 82.1%, 74.9%
non-NASH HCC (p = 0.94). No survival differences were observed in populations within
or beyond Milan. Competing-risk analysis demonstrated no differences in risk for cardiovascular-related
death (HR1.24, 95%CI 0.87–1.55, p = 0.16), or HCC recurrence-related death (HR1.21,
95%CI 0.89–1.65, p = 0.23). NASH HCC patients had lower risk of liver-related deaths
(HR0.57, 95%CI 0.34–0.98, p = 0.04).
Discussion
NASH HCC is a rising indication for liver transplantation. Despite demographic differences,
no post-transplantation survival differences were observed between NASH and non-NASH
HCC. This justifies equivalent organ allocation, irrespective of NASH status.
Abbreviations:
AFP (alpha fetoprotein), AIH (autoimmune hepatitis), BMI (body mass index), CIT (cold ischemia time), CI (confidence interval), DBD (donor after brain death), DCD (donor after cardiac death), HR (hazard ratio), HBV (hepatitis B virus), HCV (hepatitis C virus), HCC (hepatocellular carcinoma), IQR (interquartile range), LT (liver transplantation), MELD (model for end-stage liver disease), NASH (on-alcoholic steatohepatitis), OS (overall survival), PBC (primary biliary cirrhosis), PSC (primary sclerosing cholangitis), STAR (standard transplant analysis and research), US (United States), UHN (University Health Network), UNOS (United Network for Organ Sharing)To read this article in full you will need to make a payment
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References
- The natural history of nonalcoholic fatty liver disease: a population-based cohort study.Gastroenterology. 2005; 129: 113-121
- Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research.Semin Liver Dis. 2012; 32: 3-13
- Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009.Hepatology. 2015; 62: 1723-1730
- NAFLD and MAFLD as emerging causes of HCC: a populational study.JHEP Rep. 2021; 3100231
- A structured literature review of the epidemiology and disease burden of non-alcoholic steatohepatitis (NASH).Adv Ther. 2019; 36: 1574-1594
- Evolving frequency and outcomes of liver transplantation based on etiology of liver disease.Transplantation. 2013; 95: 755-760
- Hepatitis C remains leading indication for listings and receipt of liver transplantation for hepatocellular carcinoma.Dig Liver Dis. 2020; 52: 98-101
- NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances.Am J Gastroenterol. 2018; 113: 1649-1659
- Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.Hepatology. 2014; 59: 2188-2195
- High incidence of hepatocellular carcinoma and postoperative complications in patients with nonalcoholic steatohepatitis as a primary indication for deceased liver transplantation.Eur J Gastroenterol Hepatol. 2019; 31: 205-210
- Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma.BMC Cancer. 2015; 15: 210
- Lower rates of receiving model for end-stage liver disease exception and longer time to transplant among nonalcoholic steatohepatitis hepatocellular carcinoma.Liver Transplant. 2016; 22: 1356-1366
- Evidence of bias during liver transplant evaluation of non-alcoholic steatohepatitis cirrhosis patients.Liver Int. 2019; 39: 1165-1173
- Outcomes of liver transplantation for nonalcoholic steatohepatitis-associated hepatocellular carcinoma.HPB, Oxford)2021
- Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma.Transplantation. 2018; 102: 640-647
- Liver transplantation recipients with nonalcoholic steatohepatitis have lower risk hepatocellular carcinoma.Liver Transplant. 2017; 23: 1015-1022
- Transplant data: sources, collection, and caveats.Am J Transplant. 2004; 4: 13-26
- University, Health Network is continent’s top organ transplant program.Tor Star. 2018 Mar 15;
- Canadian liver transplant allocation for hepatocellular carcinoma.J Hepatol. 2019; 71: 1058-1060
- Liver allocation policies in the USA: past, present, and the future.Dig Dis Sci. 2019; 64: 985-992
- Reply to: "Canadian liver transplant allocation for hepatocellular carcinoma.J Hepatol. 2019; 71: 1060
- The impact of allocation changes on patients with hepatocellular carcinoma.Clin Liver Dis. 2020; 24: 657-663
- The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.Hepatology. 2010; 51: 1972-1978
- Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization.World J Gastroenterol. 2006; 12: 6992-6997
- Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.N Engl J Med. 1996; 334: 693-699
- Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates.Clin Gastroenterol Hepatol. 2019; 17: 748-755 e3
- Outcomes of liver transplantation for non-alcoholic steatohepatitis: a European Liver Transplant Registry study.J Hepatol. 2019; 71: 313-322
- Assessing competing risks for death following liver transplantation for hepatocellular carcinoma.Dig Dis Sci. 2019; 64: 1001-1007
- Nonalcoholic steatohepatitis becomes the leading indication for liver transplant registrants among US adults born between 1945 and 1965.J Clin Exp Hepatol. 2020; 10: 30-36
- Future trends in demand for liver transplant: birth cohort effects among patients with NASH and HCC.Transplantation. 2019; 103: 140-148
- Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease.Hepatology. 2012; 55: 1809-1819
- Time-varying impact of comorbidities on mortality after liver transplantation: a national cohort study using linked clinical and administrative data.BMJ Open. 2015; 5e006971
- Post-transplantation outcome in non-alcoholic steatohepatitis cirrhosis: comparison with alcoholic cirrhosis.Ann Hepatol. 2019; 18: 855-861
- Reduced rates of post-transplant recurrent hepatocellular carcinoma in non-alcoholic steatohepatitis: a propensity score matched analysis.Transpl Int. 2022; 3510175
- Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population.Clin Gastroenterol Hepatol. 2015; 13: 594-601 e1
- Non-alcoholic steatohepatitis: limited available treatment options but promising drugs in development and recent progress towards a regulatory approval pathway.Drugs. 2015; 75: 1373-1392
Article info
Publication history
Published online: February 02, 2023
Accepted:
January 30,
2023
Received:
November 26,
2022
Publication stage
In Press Corrected ProofFootnotes
☆This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Identification
Copyright
© 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
