This research focuses on analysing data collected as part of your usual care. Currently, the eligibility of patients with hepatocellular carcinoma for liver transplantation is based on the calculation of scores. These scores mainly take into account the volume of the tumour measured by imaging, one or more blood markers and the patient's general condition.

However, these scores do not take into account:

• the concept of downstaging (i.e. the prior reduction of tumour volume through locoregional or systemic treatments, which subsequently allows access to LT), which is becoming increasingly widespread
• the dynamics of hepatocellular carcinoma (tumour recurrence while waiting on the transplant list, administration of wait-and-see treatments)
• certain anatomopathological parameters (such as the macro-trabecular subtype of HCC).

The aim of our study is to develop a new score incorporating these factors in order to identify patients with hepatocellular carcinoma who could truly benefit from a liver transplant.

To answer the question posed in the research, data will be collected from 402 people who received a liver transplant for hepatocellular carcinoma at three hospitals in the Paris region between 1 January 2018 and 31 December 2023, and from 160 people at two international hospitals in Canada and Belgium.

Hepatocellular carcinoma (HCC) is a major public health problem. It is the fifth most common cancer and the third leading cause of cancer death worldwide. Its prevalence continues to increase and mortality associated with HCC remains high, unlike the overall cancer mortality rate. Liver transplantation (LT) remains the only curative treatment option that addresses both the tumour disease and the underlying liver disease. However, this approach presents a major challenge: the occurrence of tumour recurrence after LT, which is highly morbid. Rigorous selection for LT of candidates with HCC is essential and is currently based on standardised scores, such as AFP, Milan or Up to Seven scores, which take into account tumour volume and the patient's general condition prior to LT.

The recent arrival of immunotherapy in the management of advanced HCC has opened up new prospects for LT. In particular, the question arises as to whether LT should be offered to patients initially diagnosed with advanced HCC who have benefited from downstaging treatments, including immunotherapy.

At the same time, due to the shortage of transplants, waiting times on the LT list are getting longer in some countries and patients are increasingly receiving expectant management for their HCC. They are exposed to the risk of HCC progression or recurrence while on the list, ruling out any possibility of subsequent LT. Certain histological subtypes of HCC, particularly macrotrabecular HCC, have recently been identified as being associated with a poor prognosis, but little data is available on the risk of recurrence of these HCCs after LT raising questions about the relevance of LT for these patients.

Finally, the impact of the choice of immunosuppression on the risk of HCC recurrence after LT remains largely unexplored.

Main objective:

In accordance with TRIPOD recommendations (40), the objective is to improve the predictive scores for LT failure in patients with HCC by analysing biological, clinical, imaging and anatomopathological parameters at enrolment. This score will also include the number and type of HCC recurrences, as well as the associated expectant management. The objective is to determine the threshold of predictive score for achieving a probability of LT failure in patients of less than 20%.

Secondary objectives:

• To study overall survival and recurrence-free survival in patients with a selection score with a previously identified LT failure target (defined as removal from the LT list or recurrence after LT) <20%.
• To compare the performance of different selection scores for LT eligibility (AFP score, Milan score, Up-to-Seven, newly identified score) on LT failure rate, overall survival and recurrence-free survival in patients with HCC.
• To assess the impact of HCC recurrence and watchful waiting on TH failure rate, overall survival and recurrence-free survival in HCC patients on the LT list.
• To assess the impact of HCC subtypes, particularly macro-trabecular HCC, on LT failure rates, overall survival and recurrence-free survival in patients on the LT waiting list.
• To assess the impact of underlying liver disease etiology and the presence of portal hypertension on LT failure rates, overall survival and recurrence-free survival in patients on the LT waiting list.
• To assess the impact of modulating immunosuppressive therapy on the risk of recurrence and the occurrence of rejection in patients transplanted for HCC.

Inclusion Criteria

1. Adults (≥18 years).
2. Underwent LT for HCC between January 1, 2018 and December 31, 2023.

Exclusion Criteria

1. No evidence of HCC (imaging or histology).
2. LT performed for another intrahepatic tumor other than HCC.
3. The patient's objection to the use of their data.

We will retrospectively include patients who underwent LT for HCC between 1 January 2018 and 31 December 2023 in the Paris, Montreal and Brussels centres.

The derivation cohort will include patients from the AP-HP, while the validation cohort will include patients from the centres in Montreal and Brussels.