Recurrence of Hepatocellular Carcinoma After Liver Transplantation: The Blind Spot of HCC Management

Abstract

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) significantly impacts transplant outcomes, responsible for half of all deaths in the first 5 years after LT for HCC, with a 12-15-month median overall survival after recurrence. Recent advances in post-LT risk stratification and efficacy data of radical local treatments with curative intent support risk-adapted tailored surveillance. To date, only immunosuppressive regimen minimisation has been recognised as a potential preventive measure, although the respective roles of calcineurin inhibitor minimisation and mTOR inhibitor introduction remain inconclusive. Retrospective studies highlight the considerable heterogeneity between patients with recurrent HCC after LT in terms of timing, anatomical distribution, and applicability of treatments. Selected patients may benefit in a durable manner from local approaches with a curative intent, while tyrosine kinase inhibitors remain the first line systemic treatments. The use of immune checkpoint inhibitors is a major challenge associated with major risks of graft rejection and related mortality, that should be evaluated in prospective clinical trials. The impact on recurrent HCC of recent changes of pre-LT management, such as expanded selection criteria or the increasing use of downstaging strategies including post-ICI LT, has not been evaluated yet. Recurrent HCC after LT is a major unmet need, calling for a prospective and multicentre effort to improve outcomes for this special population.

Keywords: HCC recurrence; graft rejection; hepatocellular carcinoma; immune checkpoint inhibitors; liver transplantation; risk stratification; tyrosine kinase inhibitors.

FIGURE 1

Clinical course and management of HCC recurrence after liver transplantation. (a) Timeline illustrating the temporal incidence density of recurrence events and overall survival at 5 years post‐transplantation. Post‐transplantation survival without recurrence is 80%–85%, while approximately 15% of patients experience recurrence despite stringent selection criteria. Early recurrence (≤ 24 months) is an independent poor prognostic factor, with median survival of only 10–13 months after recurrence detection. (b) The types of recurrence (extrahepatic, combined intra‐and‐extrahepatic, and intrahepatic) with common metastatic sites (lungs, liver, and bones). (c) Major risk factors for recurrence. (d) Treatment algorithm stratified by disease pattern at recurrence. AFP: alpha foetoprotein, CNI: calcineurin inhibitors.