Citation: Brown, A.E.; Shui, A.M.; Adelmann, D.; Mehta, N.; Roll, G.R.; Hirose, R.; Syed, S.M. Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation. Cancers 2023, 15, 620. https://doi.org/10.3390/ cancers15030620 Academic Editor: Tomoharu Yoshizumi Received: 20 December 2022 Revised: 12 January 2023 Accepted: 17 January 2023 Published: 19 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation Audrey E. Brown 1, * , Amy M. Shui 2 , Dieter Adelmann 3 , Neil Mehta 4 , Garrett R. Roll 5 , Ryutaro Hirose 5 and Shareef M. Syed 5 1 Department of Surgery, University of California, San Francisco, CA 94143, USA 2 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA 3 Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94143, USA 4 Department of Gastroenterology, University of California, San Francisco, CA 94143, USA 5 Department of Transplant Surgery, University of California, San Francisco, CA 94143, USA * Correspondence: audrey.brown@ucsf.edu Simple Summary: This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant. We sought to understand the impact that the number and type of local regional therapies (LRTs) have on peri-operative outcomes and complications after liver transplantation. The patients who received more than 3 LRTs prior to a liver transplant had a higher risk of biliary leak but otherwise similar outcomes to those who received fewer LRTs. Abstract: The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is un- known. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution- specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings. Keywords: liver transplantation; hepatocellular carcinoma; local regional therapy; biliary complications; arterial complications 1. Introduction Liver transplant has long been established as the gold-standard therapy for patients with localized hepatocellular carcinoma (HCC) not amenable to resection [1]. In 2002, the Milan Criteria were adopted by the United Network for Organ Sharing (UNOS), introducing exception points for HCC patients, and in 2015, the Organ Procurement and Transplantation Network (OPTN) implemented a policy change that required a mandatory wait time of 6 months prior to listing for a liver transplant. The average wait time for liver transplant varies widely by UNOS region, but for at least 65% of patients, the wait time exceeds 6 months, and for many patients, the wait time has gotten longer over time [2]. Cancers 2023, 15, 620. https://doi.org/10.3390/cancers15030620 https://www.mdpi.com/journal/cancers