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

Elizabeth C Verna; Meaghan M Phipps; Karim J Halazun; Daniela Markovic; Sander S Florman; Brandy M Haydel; Richard Ruiz; Goran Klintmalm; David D Lee; Burcin Taner; Maarouf A Hoteit; Amit D Tevar; Abhinav Humar; William C Chapman; Neeta Vachharajani; Federico N Aucejo; Marc L Melcher; Mindie H Nguyen; Trevor L Nydam; James F Markmann; Constance Mobley; Rafik M Ghobrial; Alan N Langnas; Carol Carney; Jennifer Berumen; Gabriel T Schnickel; Debra Sudan; Johnny C Hong; Abbas Rana; Christopher M Jones; Thomas M Fishbein; Ronald W Busuttil; Vatche Agopian; US Multicenter HCC Transplant Consortium

doi:10.1097/LVT.0000000000000007

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

Liver Transpl. 2023 Jan 1;29(1):34-47. doi: 10.1097/LVT.0000000000000007. Epub 2022 Dec 23.

Authors

Elizabeth C Verna¹, Meaghan M Phipps¹, Karim J Halazun², Daniela Markovic³, Sander S Florman⁴, Brandy M Haydel⁴, Richard Ruiz⁵, Goran Klintmalm⁵, David D Lee⁶, Burcin Taner⁶, Maarouf A Hoteit⁷, Amit D Tevar⁸, Abhinav Humar⁸, William C Chapman⁹, Neeta Vachharajani⁹, Federico N Aucejo¹⁰, Marc L Melcher¹¹, Mindie H Nguyen¹², Trevor L Nydam¹³, James F Markmann¹⁴, Constance Mobley¹⁵, Rafik M Ghobrial¹⁵, Alan N Langnas¹⁶, Carol Carney¹⁶, Jennifer Berumen¹⁷, Gabriel T Schnickel¹⁷, Debra Sudan¹⁸, Johnny C Hong¹⁹, Abbas Rana²⁰, Christopher M Jones²¹, Thomas M Fishbein²², Ronald W Busuttil²³, Vatche Agopian²³; US Multicenter HCC Transplant Consortium

Affiliations

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.

PMID: 36630156
DOI: 10.1097/LVT.0000000000000007

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.

Publication types

Multicenter Study

MeSH terms

Adult
Carcinoma, Hepatocellular* / epidemiology
Carcinoma, Hepatocellular* / pathology
Carcinoma, Hepatocellular* / surgery
Humans
Liver Neoplasms* / epidemiology
Liver Neoplasms* / pathology
Liver Neoplasms* / surgery
Liver Transplantation* / adverse effects
Neoplasm Recurrence, Local / pathology
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / surgery
Retrospective Studies
Risk Factors