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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study
William Chung, Kevin Wong, Noel Ravindranayagam, Lauren Tang, Josephine Grace, Darren Wong, Danny Con, Marie Sinclair, Avik Majumdar, Numan Kutaiba, Samuel Hui, Paul Gow, Vijayaragavan Muralidharan, Alexander Dobrovic, Adam Testro
William Chung, Kevin Wong, Noel Ravindranayagam, Lauren Tang, Josephine Grace, Darren Wong, Danny Con, Marie Sinclair, Avik Majumdar, Samuel Hui, Paul Gow, Adam Testro, Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia
William Chung, Lauren Tang, Josephine Grace, Darren Wong, Marie Sinclair, Avik Majumdar, Paul Gow, Adam Testro, Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
Numan Kutaiba, Department of Radiology, Austin Health, Heidelberg 3084, Victoria, Australia
Samuel Hui, Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
Vijayaragavan Muralidharan, Department of Surgery, University of Melbourne, Austin Health, Heidelberg 3048, Victoria, Australia
Alexander Dobrovic, Department of Surgery, Beacon Laboratory, Austin Precinct, The University of Melbourne, Austin Hospital, Heidelberg 3048, Victoria, Australia
Author contributions: Chung W contributed to study design, data collection, statistical analysis, manuscript writing and revision; Wong K, Ravindranayagam N and Tang L contributed to data collection; Grace J, Wong D, Sinclair M, Majumdar A, Kutaiba N, Gow P, Muralidharan V, Dobrovic A and Testro A contributed to study design, assisted with statistical analysis, and provided critical appraisal of the manuscript; Con D and Hui S contributed to assisted with statistical analysis of the study and critical appraisal of manuscript.
Institutional review board statement: This study was approved by the Austin Health Human Ethics Research Committee (No. HREC/87459/Austin-2022).
Informed consent statement: As this was a retrospective study by medical records review, informed consent was not obtained from study participants.
Conflict-of-interest statement: Dobrovic A has received honoraria as a speaker from Bio-Rad. Chung W, Wong K, Ravindranayagam N, Tang L, Grace J, Wong D, Con D, Sinclair M, Majumdar A, Kutaiba N, Hui S, Gow P, Muralidharan V and Testro A do not have any conflicts of interests to declare.
Data sharing statement: De-identified patient data may be provided upon request at william.chung2@austin.org.au.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: William Chung, FRACP, MBBS, Attending Doctor, Doctor, Research Fellow, Staff Physician, Department of Gastroenterology, Austin Health, No. 145 Studley Road, Heidelberg 3084, Victoria, Australia. william.chung2@austin.org.au
Received: March 28, 2024
Revised: May 13, 2024
Accepted: May 30, 2024
Published online: September 18, 2024
Processing time: 125 Days and 7.5 Hours
BACKGROUND
Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.
AIM
To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT.
METHODS
This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing.
RESULTS
Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes.
CONCLUSION
Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.
Core Tip: In this single centre, retrospective study of adult patients who received liver transplantation (LT) for Hepatocellular carcinoma in Australia, statin, aspirin or metformin use after LT was not associated with a difference in the composite endpoint of hepatocellular carcinoma (HCC)-recurrence and all-cause mortality, HCC-recurrence or HCC-related mortality.
