Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study

Edison Xu; Parissa Tabrizian; Julio Gutierrez; Maarouf Hoteit; Tara Ghaziani; Kali Zhou; Neehar Parikh; Veeral Ajmera; Elizabeth Aby; Amy Shui; Rebecca Marino; Allison Martin; Christopher Wong; Karissa Kao; Shravan Dave; Sander Florman; Francis Yao; Neil Mehta

doi:10.1097/HEP.0000000000001231

Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study

Hepatology. 2025 Jan 14. doi: 10.1097/HEP.0000000000001231. Online ahead of print.

Authors

Edison Xu¹, Parissa Tabrizian², Julio Gutierrez³, Maarouf Hoteit⁴, Tara Ghaziani⁵, Kali Zhou⁶, Neehar Parikh⁷, Veeral Ajmera⁸, Elizabeth Aby⁹, Amy Shui¹⁰, Rebecca Marino², Allison Martin³, Christopher Wong⁶, Karissa Kao⁷, Shravan Dave⁸, Sander Florman², Francis Yao¹⁰, Neil Mehta¹⁰

Affiliations

¹ Department of Medicine, University of California, San Francisco, San Francisco, CA.
² Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY.
³ Center of Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, CA.
⁴ Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA.
⁵ Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA.
⁶ Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles CA.
⁷ Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.
⁸ Division of Gastroenterology and Hepatology, University of California, San Diego, San Diego, CA.
⁹ Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN.
¹⁰ Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA.

PMID: 39808828
DOI: 10.1097/HEP.0000000000001231

Abstract

Background aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate downstaging and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL;p=0.08), MELD (9 vs. 9;p=0.52), and Child-Pugh (A vs. A;p=0.30). At 2 years from first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged (p<0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion<10, 51% for sum 10-12, and 39% for sum>12 (p=0.01). Y-90 achieved higher DS success than transarterial chemoembolization (TACE) in AC (74% vs. 65%;p<0.001). 48% of UNOS-DS and 40% of AC underwent LT (p=0.10). 5-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%;p=0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%;p=0.02).

Conclusions: Despite higher HCC recurrence and lower ITT survival in AC, post-LT survival was comparable between UNOS-DS and AC. Y-90 attained higher DS success than TACE in AC. LT after downstaging is feasible in AC, though defining an upper limit in tumor burden may be necessary.