Pahari H, Peer JA, Tripathi S, Singhvi SK, Dhir U. Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand? World J Gastrointest Pharmacol Ther 2024; 15(5): 97570 [DOI: 10.4292/wjgpt.v15.i5.97570]
Corresponding Author of This Article
Hirak Pahari, DNB, MBBS, Surgeon, Department of Liver Transplant and Hepatobiliary Surgery, Sir Ganga Ram Hospital, Old Rajinder Nagar, New Delhi 110060, Delhi, India. hirak.pahari@gmail.com
Research Domain of This Article
Transplantation
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Pharmacol Ther. Sep 5, 2024; 15(5): 97570 Published online Sep 5, 2024. doi: 10.4292/wjgpt.v15.i5.97570
Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand?
Hirak Pahari, Javid A Peer, Shikhar Tripathi, Suresh K Singhvi, Ushast Dhir
Hirak Pahari, Suresh K Singhvi, Ushast Dhir, Department of Liver Transplant and Hepatobiliary Surgery, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India
Javid A Peer, Shikhar Tripathi, Department of Surgical Gastroenterology and Liver Transplant, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India
Author contributions: Pahari H and Peer JA devised the concept; Pahari H, Peer JA and Tripathi S performed the research and literature review; Tripathi S, Singhvi S and Dhir U completed the manuscript; Singhvi S and Dhir U prepared the tables and figure; Pahari H, Peer JA and Tripathi S reviewed and revised the manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest to disclose.
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: Hirak Pahari, DNB, MBBS, Surgeon, Department of Liver Transplant and Hepatobiliary Surgery, Sir Ganga Ram Hospital, Old Rajinder Nagar, New Delhi 110060, Delhi, India. hirak.pahari@gmail.com
Received: June 2, 2024 Revised: August 22, 2024 Accepted: August 28, 2024 Published online: September 5, 2024 Processing time: 92 Days and 15.3 Hours
Abstract
Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.
Core Tip: The advent of immune checkpoint inhibitors as a downstaging therapy has been followed with great interest since the results of the IMBRAVE study, especially for multifocal hepatocellular carcinoma beyond criteria and certain cases with portal vein tumor thrombosis. Multiple case reports have shown benefit but with a degree of caution. Our review aims to identify the key points and recommendations for the safe usage of these life-saving immunomodulators in the setting of liver transplantation using the current available literature.
