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@article{Bhoori:2026:10.1016/j.jhep.2026.02.019,
author = {Bhoori, S and Rivoltini, L and Pinato, DJ and Bellia, V and Maspero, M and Bongini, M and de, Cristofaro J and Vaiani, M and Dosi, M and Vergani, E and Vergani, B and Leoncini, G and Daveri, E and Di, Maio G and Simonotti, N and Cappetti, B and Cova, A and Rini, F and Bergamini, S and Lalli, L and Sposito, C and Mazzaferro, V},
doi = {10.1016/j.jhep.2026.02.019},
journal = {J Hepatol},
pages = {117--129},
title = {Efficacy of liver transplantation after response to atezolizumab-bevacizumab downstaging of intermediate and advanced hepatocellular carcinoma (ImmunoXXL).},
url = {http://dx.doi.org/10.1016/j.jhep.2026.02.019},
volume = {85},
year = {2026}
}
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TY  - JOUR
AB  - BACKGROUND & AIMS: Liver transplantation (LT) is a curative treatment option in early and intermediate hepatocellular carcinoma (HCC) following downstaging with locoregional therapies (LRT). Tumor response to immune checkpoint inhibitors may extend LT eligibility to intermediate and advanced stages. METHODS: In this prospective phase II study, patients with intermediate and advanced HCCs beyond extended transplant criteria, not amenable to further LRTs, were downstaged with atezolizumab-bevacizumab (Atezo-Bev) prior to LT. The primary endpoint was recurrence-free survival with safety and efficacy as additional outcomes. Spectral quantitative pathology and immune signatures in tumor tissue and peripheral blood were studied longitudinally. RESULTS: Sixteen patients with HCC beyond expanded transplant criteria (median tumor size 6.5 cm [IQR 3-8], median AFP 283 ng/ml [IQR 6-1,080], portal vein thrombosis 50%) were downstaged to LT after a median of 4.7 months (IQR 2.4-7.6). Prior LRTs were used in 15 (94%) patients. The washout period from the last Atezo-Bev dose to transplant was 57.5 (IQR 29-87) days. Median follow-up was 16 months (95% CI 4-22). Pre-transplant immune-related adverse events occurred in 3 (19%) patients and post-transplant acute rejection in 4 (25%). Post-LT 90-day morbidity and mortality were 62.5% (95% CI 35-85%) and 6.3% (95% CI 0.2-30%) respectively. Explant pathology revealed 10 complete and 6 partial responses. Responding patients harboured a tumor microenvironment with features suggestive of immune activation/extinguishment, correlated with duration of Atezo-Bev treatment and length of pre-LT washout. One (6.2%) HCC post-LT recurrence occurred during follow-up. Recurrence-free and post-transplant overall survival were 90% and 94% after 2 years, respectively. CONCLUSIONS: LT following Atezo-Bev downstaging achieves promising recurrence-free survival in intermediate and advanced HCC beyond conventional transplant criteria. Acute rejection see
AU  - Bhoori,S
AU  - Rivoltini,L
AU  - Pinato,DJ
AU  - Bellia,V
AU  - Maspero,M
AU  - Bongini,M
AU  - de,Cristofaro J
AU  - Vaiani,M
AU  - Dosi,M
AU  - Vergani,E
AU  - Vergani,B
AU  - Leoncini,G
AU  - Daveri,E
AU  - Di,Maio G
AU  - Simonotti,N
AU  - Cappetti,B
AU  - Cova,A
AU  - Rini,F
AU  - Bergamini,S
AU  - Lalli,L
AU  - Sposito,C
AU  - Mazzaferro,V
DO  - 10.1016/j.jhep.2026.02.019
EP  - 129
PY  - 2026///
SP  - 117
TI  - Efficacy of liver transplantation after response to atezolizumab-bevacizumab downstaging of intermediate and advanced hepatocellular carcinoma (ImmunoXXL).
T2  - J Hepatol
UR  - http://dx.doi.org/10.1016/j.jhep.2026.02.019
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41763363
VL  - 85
ER  -
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