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Transplantation. 2022 Jan 01;106(1):106-116. doi: 10.1097/TP.0000000000003681.

Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation.

Transplantation

Oren Shaked, Jack Demetris, Josh Levitsky, Sandy Feng, Bao-Li Loza, Jeff Punch, Jorge Reyes, Goran Klintmalm, Whitney Jackson, Michele DesMarais, Peter Sayre, Abraham Shaked, K Rajender Reddy

Affiliations

  1. Department of Surgery, University of California San Francisco, San Francisco, CA.
  2. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
  3. Division of Hepatology and Comprehensive Transplant Center, Northwestern Memorial Hospital, Chicago, IL.
  4. Department of Surgery, University of Pennsylvania, Philadelphia, PA.
  5. Department of Surgery, University of Michigan, Ann Arbor, MI.
  6. Department of Surgery, University of Washington, Seattle, WA.
  7. Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
  8. Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO.
  9. Immune Tolerance Network, San Francisco, CA.
  10. Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA.

PMID: 33982909 PMCID: PMC8349377 DOI: 10.1097/TP.0000000000003681

Abstract

BACKGROUND: Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

METHODS: Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist.

RESULTS: One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis.

CONCLUSIONS: In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Conflict of interest statement

K.R.R. received advisory board from Abbvie, Gilead, Merck, BMS, Spark Therapeutics, Dova, Shionogi, and Mallinckrodt and research grants (paid to the University of Pennsylvania) from Merck, Gilead, Ma

References

  1. Davern TJ, Lake JR. Recurrent disease after liver transplantation. Semin Gastrointest Dis. 1998;9:86–109. - PubMed
  2. Agopian VG, Kaldas FM, Hong JC, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg. 2012;256:624–633. - PubMed
  3. Younossi ZM, Stepanova M, Afendy M, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011;9:524–530.e1; quiz e60. - PubMed
  4. Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141:1249–1253. - PubMed
  5. Marsman WA, Wiesner RH, Rodriguez L, et al. Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation. 1996;62:1246–1251. - PubMed
  6. Andert A, Ulmer TF, Schöning W, et al. Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation. Hepatobiliary Pancreat Dis Int. 2017;16:617–623. - PubMed
  7. Dumortier J, Giostra E, Belbouab S, et al. Non-alcoholic fatty liver disease in liver transplant recipients: another story of “seed and soil”. Am J Gastroenterol. 2010;105:613–620. - PubMed
  8. Dureja P, Mellinger J, Agni R, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011;91:684–689. - PubMed
  9. Kim H, Lee K, Lee KW, et al. Histologically proven non-alcoholic fatty liver disease and clinically related factors in recipients after liver transplantation. Clin Transplant. 2014;28:521–529. - PubMed
  10. Shaked A, DesMarais MR, Kopetskie H, et al. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. Am J Transplant. 2019;19:1397–1409. - PubMed
  11. Brunt EM, Kleiner DE, Wilson LA, et al.; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53:810–820. - PubMed
  12. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699. - PubMed
  13. Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis c virus infection as the leading indication for liver transplantation in the United States. Clin Gasterentol Hepatol. 2018;16:1356–1358. - PubMed
  14. Gitto S, de Maria N, di Benedetto F, et al. De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients. Eur J Gastroenterol Hepatol. 2018;30:766–773. - PubMed
  15. Idowu MO, Chhatrala R, Siddiqui MB, et al. De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients. Liver Transpl. 2015;21:1395–1402. - PubMed
  16. Bhagat V, Mindikoglu AL, Nudo CG, et al. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl. 2009;15:1814–1820. - PubMed
  17. Hejlova I, Honsova E, Sticova E, et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016;22:644–655. - PubMed
  18. Seo S, Maganti K, Khehra M, et al. De novo nonalcoholic fatty liver disease after liver transplantation. Liver Transpl. 2007;13:844–847. - PubMed
  19. Vallin M, Guillaud O, Boillot O, et al. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014;20:1064–1071. - PubMed
  20. Arguello G, Balboa E, Arrese M, et al. Recent insights on the role of cholesterol in non-alcoholic fatty liver disease. Biochim Biophys Acta. 2015;1852:1765–1778. - PubMed
  21. Hałoń A, Patrzałek D, Rabczyński J. Hepatic steatosis in liver transplant donors: rare phenomenon or common feature of donor population? Transplant Proc. 2006;38:193–195. - PubMed
  22. Jamieson RW, Zilvetti M, Roy D, et al. Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model. Transplantation. 2011;92:289–295. - PubMed
  23. Galvin Z, Rajakumar R, Chen E, et al. Predictors of de novo nonalcoholic fatty liver disease after liver transplantation and associated fibrosis. Liver Transpl. 2019;25:56–67. - PubMed
  24. Yalamanchili K, Saadeh S, Klintmalm GB, et al. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease. Liver Transpl. 2010;16:431–439. - PubMed
  25. Watt KD. Metabolic syndrome: is immunosuppression to blame? Liver Transpl. 2011;17(Suppl 3):S38–S42. - PubMed

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