Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium

Author:

Verna Elizabeth C.1ORCID,Phipps Meaghan M.1ORCID,Halazun Karim J.2ORCID,Markovic Daniela3,Florman Sander S.4,Haydel Brandy M.4,Ruiz Richard5,Klintmalm Goran5ORCID,Lee David D.6ORCID,Taner Burcin6ORCID,Hoteit Maarouf A.7,Tevar Amit D.8,Humar Abhinav8ORCID,Chapman William C.9,Vachharajani Neeta9,Aucejo Federico N.10,Melcher Marc L.11ORCID,Nguyen Mindie H.12,Nydam Trevor L.13,Markmann James F.14,Mobley Constance15ORCID,Ghobrial Rafik M.15,Langnas Alan N.16,Carol Carney 16,Berumen Jennifer17,Schnickel Gabriel T.17ORCID,Sudan Debra18,Hong Johnny C.19,Rana Abbas20,Jones Christopher M.21,Fishbein Thomas M.22,Busuttil Ronald W.23,Agopian Vatche23,

Affiliation:

1. Department of Medicine, Division of Digestive and Liver Diseases, Columbia University, New York, New York, USA

2. Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Weill Cornell Medicine, New York, New York, USA

3. Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

4. Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, New York, USA

5. Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA

6. Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA

7. Penn Transplant Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA

8. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

9. Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA

10. Cleveland Clinic Foundation, Cleveland, Ohio, USA

11. Department of Surgery, Stanford University, Palo Alto, California, USA

12. Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA

13. Department of Surgery, Division of Transplant Surgery, University of Colorado School of Medicine, Denver, Colorado, USA

14. Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

15. Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, Texas, USA

16. Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA

17. Department of Surgery, Division of Transplantation and Hepatobiliary Surgery, University of California, San Diego, California, USA

18. Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

19. Department of Surgery, Division of Transplant Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

20. Department of Surgery, Baylor College of Medicine, Houston, Texas, USA

21. Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA

22. Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia, USA

23. Department of Surgery, Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Abstract

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Transplantation,Hepatology,Surgery

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