Immunotherapy as a bridge to liver transplantation for hepatocellular carcinoma, a multi centric experience

Introduction: Immune-checkpoint inhibitors (ICIs) increasingly downstage hepatocellular carcinoma
(HCC) to liver transplantation (LT), but their sustained immune activation may heighten the risk of graft
rejection when given before or after transplant. Evidence remains limited to small and heterogeneous studies,
suggesting higher rejection rates with short wash-out intervals. More data are needed to define safe timing
and immunosuppression strategies around transplantation in ICI-exposed patients. Therefore, real-world
multicentre data are needed.
Aim: We aim to evaluate the impact of immunotherapy on graft outcomes, the risk for rejection and post-
transplant HCC recurrence.
Methods: We retrospectively collected data from patients treated with ICIs between January 2020 and October
2025 who underwent liver transplantation in all transplant centres in Belgium and in Beaujon Hospital, Paris.
We collected demographic data, pre-transplant HCC characteristics (number and size of nodules, alpha-
fetoprotein levels), and post-transplant outcomes.
Results: We collected data from 15 patients. The cohort consisted predominantly of men (80%), with a mean
age at LT of 55.6 ± 12.3 years. Cirrhosis was mainly of viral origin (40%), and alcohol-related liver disease
accounted for 20%. The mean MELD score was 12.1 ± 4.3, and most patients were classified as Child–Pugh
A. The mean ALBI score was −2.2 ± 0.8. At HCC diagnosis, patients had on average 2.1 nodules, and the
median size of the largest lesion was 55 mm (range 24–119). BCLC stage was B in most patients (80%),
while two were classified as BCLC C and one as BCLC D. Mean alpha-fetoprotein at LT was 29.9 ng/mL.
All but one patient received Atezolizumab plus Bevacizumab before LT. One patient received Durvalumab
for a mixed HCC–iCCA lesion with predominant intrahepatic cholangiocarcinoma features. The median
washout period between immunotherapy and LT was 5 months (range 1–23). The mean interval between
HCC diagnosis and LT was 27.4 ± 19.6 months. Six patients (40%) underwent additional bridging therapies
(radio- or chemoembolization, external radiotherapy, microwave ablation, etc.). On the liver explants (N =
12), 30% were classified as disease-free (pT0N0) and 30% as pT1 (a or b) N0. Two patients were pT2N0 and
two were pT3N0. After a median follow-up of 10 months (range 1–32), two patients developed recurrence at
5.5- and 13-months post-LT, respectively. One patient had been classified as pT3N0 and the other as pT1bN0
with poorly differentiated HCC. The latter patient died from oncological progression despite salvage chemo
and immunotherapy. Early allograft rejection within the first postoperative month occurred in two patients,
both successfully treated with steroids. Among the 11 patients with available data on induction therapy, 8
received Basiliximab. Six patients are currently maintained on tacrolimus monotherapy without additional
immunosuppressive agents.
Conclusions: Immunotherapy prior to liver transplantation appears feasible in carefully selected patients, with
acceptable rates of rejection and early post-transplant outcomes. In our cohort, ICIs effectively contributed
to tumour control and downstaging, enabling access to LT in patients with advanced HCC. However, longer
follow-up and larger prospective studies are required to better assess the long-term risk of recurrence and to
refine optimal timing and immunosuppression strategies in ICI-exposed candidates