INTRODUCTION:Primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are one of the leading causes of cancer-related mortality. Transarterial chemoembolisation (TACE) and radioembolisation (TARE) are established palliative treatments yet they are traditionally performed during inpatient hospitalisation. Recent technical and organisational advances allow for safe same-day ambulatory procedures. In particular, the extent to which ambulatory intra-arterial therapy aligns with patients' expectations, comfort and quality of life remains poorly documented. The Care pathway for Hepatic intra-arterial Oncology in an ambulatory Context study (CHOC) trial aims to evaluate the implementation and effectiveness from both patient-centred and clinical perspectives of an ambulatory care pathway for intra-arterial treatment of primary liver cancer in a multicentre randomised hybrid type 1 trial. METHODS AND ANALYSIS:CHOC is a pragmatic, multicentre, randomised controlled hybrid type 1 trial comparing ambulatory versus conventional inpatient care for patients undergoing TACE or TARE for primary liver cancer. A total of 206 patients (103 per arm) will be randomised 1:1 and followed for 7 months. The primary outcome is the patient's global satisfaction score, measured 3 days post-procedure using the EORTC PATSAT-C33 questionnaire. Secondary outcomes include quality of life, safety, clinical outcomes, cost analysis and an embedded qualitative implementation study assessing acceptability, adoption, feasibility and sustainability across centres. Economic analyses will estimate both per-patient costs and the 5-year budget impact for the French national health insurance. ETHICS AND DISSEMINATION:The study has received ethical approval from the Protection of Persons Committee and adheres to the Declaration of Helsinki, good clinical practice and French regulatory requirements. Findings will be disseminated through peer-reviewed publications, conferences and participating centres to guide broader implementation of ambulatory interventional radiology care. TRIAL REGISTRATION NUMBER:NCT06990659.

The use of immune checkpoint inhibitors (ICIs) after liver transplantation (LT) remains controversial due to rejection risk. This study aims to characterize patients receiving ICIs post-LT and identify the risk factors for rejection. This retrospective, multicenter study included patients who received at least one ICI (anti-programmed cell death 1, anti-programmed cell death ligand 1, or anti-cytotoxic T cell-associated protein 4) post-LT. Fifty-two patients were included (77% male), median age 66 (interquartile range [IQR], 57.5-69.7) years at ICI initiation. The median interval between LT and ICI was 4.5 (IQR, 2.6-9.9) years. ICIs were administered for hepatocellular carcinoma recurrence (62%) or de novo cancer (38%), with similar rejection and survival rates. Rejection occurred in 7 patients (13%) and was moderate/severe, developing at a median of 27 (IQR, 23-57) days post-ICI. The increase of immunosuppression and calcineurin inhibitor use at ICI initiation was associated with reduced rejection risk (P = .04 and P = .013, respectively). Rejection was associated with significantly lower survival (P = .0003). Overall survival following the introduction of ICI at 3, 6, and 12 months was 65%, 46.9%, and 38.9%, respectively. Rejection post-ICI occurs less frequently than previously reported, but early after therapy initiation, it is severe and linked to the absence of calcineurin inhibitors. Optimizing immunosuppression may enhance the safety of ICI use in transplant recipients.

BACKGROUND:Invasive aspergillosis is a rare but severe complication of liver transplantation. Incidence varies from 1·2% to 5·6% and mortality is greater than 50%. Few studies have investigated this complication. We aimed to describe cases of, and identify the factors associated with, invasive aspergillosis occurrence and mortality. METHODS:This nationwide, retrospective, matched case-control study included cases of invasive aspergillosis occurring after liver transplantation between Jan 1, 2007, and Dec 31, 2021, matched 1:1 on centre and transplantation period to control individuals without invasive aspergillosis across 15 liver transplantation centres in France. Cases were patients aged 18 years or older who presented with proven or probable invasive aspergillosis. The matched control was the next patient who received a transplant at the same transplantation centre after the case. Cases were retrospectively identified in each centre using the mycology laboratory database and the French Medicalised Information System Programme. Data were retrieved from hospital charts. The primary outcome was the identification of risk factors associated with the development of invasive aspergillosis following liver transplantation. Multivariable analysis using conditional logistic regression with a random effect for study centres was done to establish risk factors. FINDINGS:Among 14 332 liver transplantations, 196 recipients with invasive aspergillosis (62 [32%] female and 134 [68%] male) were identified and matched with 196 control individuals (54 [28%] female and 142 [73%] male). Invasive aspergillosis occurred at a median of 29 days (IQR 7-173) after liver transplantation. Risk factors for developing invasive aspergillosis were history of chronic kidney disease (adjusted odds ratio 4·13 [95% CI 2·35-7·24]), liver transplantation for acute liver disease (3·41 [1·44-8·06]), post-liver transplantation renal replacement therapy (3·82 [1·96-7·42]), and post-liver transplantation vasopressor support for longer than 24 h (2·82 [1·70-4·68]). INTERPRETATION:This study identifies three patient populations at risk of invasive aspergillosis after liver transplantation: patients with history of chronic kidney disease, those who have received a transplant for acute liver disease, and those who had a post-operative period marked by organ failure. This identification could lead to new invasive aspergillosis prophylactic strategies. FUNDING:None.

PURPOSE: Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises in a context of chronic inflammation driven by metabolic dysfunction, long-term alcohol use, viral hepatitis, and other etiologies. This study aimed to investigate whether intrahepatic and circulating immune profiles in HCC patients correlate with patient characteristics or clinical parameters. METHODS: Fresh tumor tissue, paired non-tumor liver tissue, and peripheral blood samples from 93 patients with HCC were analyzed using multiparametric flow cytometry to characterize lymphocyte subsets (T cells, NK cells, NKT cells, and B cells), immune checkpoint molecule expression (ICOS, 4-1BB, OX40, PD-1, TIM-3, LAG-3, and CTLA-4), and activation status. Associations between immune parameters and patient demographic or clinical features were assessed. RESULTS: Circulating alpha-fetoprotein (AFP) levels positively correlated with tumor-infiltrating PD-1high CD8+ T cell frequency (r=0.45, p<0.0001), but this correlation was not observed in non-tumoral or circulating compartments. CONCLUSION: AFP-producing HCC is linked to intra-tumoral immune exhaustion, marked by PD-1high CD8+ T cell accumulation, suggesting a localized immunosuppressive effect mediated by tumor-secreted AFP.

LBA479 Background: At a preplanned interim analysis of CheckMate 9DW (NCT04039607), with 35.2 months of median follow-up, nivolumab plus ipilimumab (NIVO + IPI) demonstrated significant overall survival (OS) benefit vs lenvatinib or sorafenib (LEN/SOR) (hazard ratio [HR] 0.79 [95% CI, 0.65–0.96]; P = 0.0180), higher objective response rate (ORR; 36% vs 13%, P < 0.0001) with durable responses, and manageable safety in patients (pts) with previously untreated unresectable HCC (Yau T et al. Lancet 2025;405:1851–64). Based on these results, NIVO + IPI combination was approved as a first-line (1L) treatment for unresectable HCC by the US FDA, European Commission, and in other countries. We report updated efficacy and safety results at a median follow-up of 4 years. Methods: Adults with previously untreated histologically confirmed advanced HCC, either ineligible for or having progressed after curative surgical/locoregional therapies, ≤ 1 measurable untreated lesion per RECIST v1.1, Child–Pugh score 5 or 6, and ECOG performance status 0 or 1 were included. Pts were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles) followed by NIVO 480 mg Q4W or investigator’s choice of SOR 400 mg BID or LEN 8 mg or 12 mg QD until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was OS; secondary endpoints included ORR and duration of response (DOR) per blinded independent central review (BICR). Results: A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated in the LEN/SOR arm, 275 (85%) received LEN. After a median (range) follow-up of 52.5 (44.0–66.1) months, NIVO + IPI continued to show OS benefit vs LEN/SOR (HR, 0.78; 95% CI, 0.65–0.93), with higher 48-month OS rates (31% vs 18%; Table). ORR was higher with NIVO + IPI vs LEN/SOR (36% vs 13%), with higher complete response rates (8% vs 2%, respectively) and durable responses (median DOR, 34.3 vs 12.9 months, respectively; Table). A summary of treatment-related adverse events (TRAEs) is shown in the Table. Conclusions: After 4 years of follow-up, 1L NIVO + IPI continued to show sustained efficacy benefit vs LEN/SOR in unresectable HCC and manageable safety with no new concerns. These results continue to support NIVO + IPI as a standard-of-care treatment in these patients. Clinical trial information: NCT04039607 . Efficacy NIVO + IPI(n = 335) LEN/SOR(n = 333) Median OS (95% CI), mo 23.7 (18.8–29.4) 20.6 (17.7–22.5) HR (95% CI) 0.78 (0.65–0.93) 48-mo OS rate (95% CI), % 31 (26–36) 18 (14–23) ORR, a n (%); (95% CI) 122 (36); 31–42 44 (13); 10–17 Median DOR a,b (95% CI), mo 34.3 (22.6–47.7) 12.9 (10.2–33.9) Safety, n (%) (n = 332) (n = 325) Any-grade/grade 3–4 TRAEs 277 (83)/136 (41) 297 (91)/138 (142) Any-grade/grade 3–4 TRAEs leading to discontinuation 59 (18)/44 (13) 34 (10)/21 (6) a Per BICR. b In responders only.

BACKGROUND & AIMS:Hepatitis B, caused by the Hepatitis B virus (HBV), is a significant global health concern, often leading to chronic hepatitis B in individuals unable to mount an effective immune response. Chronic HBV substantially increases the risk of severe liver diseases, including cirrhosis and hepatocellular carcinoma. Dendritic cells (DC) and Natural killer (NK) cells play crucial roles in the early immune response to HBV, but their function is compromised in chronic hepatitis B patients. We investigated how Hepatitis B surface antigen (HBsAg) influences the interplay between DC subpopulations and NK cells. METHODS:Blood-derived DC subsets were pre-exposed to HBsAg and then co-cultured with NK cells under various stimulation conditions. We subsequently evaluated the modulations of DC, and the phenotypic and functional responses of NK cells. Similarly, DC subsets were exposed to serum from HBV-infected individuals with varying levels of HBsAg or directly purified from HBV patients to assess their ability to stimulate NK cell responses. RESULTS:Our findings show that HBsAg disrupts cDC2-mediated NK cell activation through Toll-like receptor (TLR)7/8-dependent pathways and cDC1-mediated NK cell degranulation via TLR3-dependent mechanisms. Exposure of pDC to HBsAg alters NK cell activation, phenotype and degranulation through TLR9-dependent pathways. This impairment was recapitulated following exposure to serum from HBV-infected patients in an HBsAg-dependent manner. Consistently, circulating HBsAg in patients with chronic HBV infection was associated with impaired pDC-mediated NK cell cytotoxicity. CONCLUSIONS:These results uncover key mechanisms by which HBsAg modulates pDC-NK cell interactions, shedding light on how HBV evades innate immune responses and contributes to immune dysfunction.

Liver surface nodularity (LSN) is a recognized non-invasive biomarker of cirrhosis. This study introduces auto-LSN, an artificial intelligence (AI)-based algorithm for fully automated LSN quantification, assesses its association with fibrosis stage and its non-inferiority in diagnostic performance for advanced chronic liver disease (ACLD) and cirrhosis compared to the FDA-approved, semi-automated liver boundary analysis (LBA) software. This retrospective, bicentric study included patients with chronic liver disease risk factors who underwent CT and liver biopsy between April 2014 and March 2020. Fibrosis stages were grouped into F3–F4 (ACLD) vs F0–F2, and F4 (cirrhosis) vs F0–F3 per the METAVIR. LSN was measured with auto-LSN and LBA. Their association with fibrosis grade and diagnostic accuracy for ACLD and cirrhosis were compared using a −0.05 non-inferiority margin. Mann–Whitney–Wilcoxon tests, Spearman correlation, and area under the receiver operating characteristic curve (AUC) were used. In 127 patients (68 ± 12 years; 97 men), auto-LSN demonstrated a positive correlation with fibrosis stage (ρ = 0.59; 95

4197 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by aggressive tumor dissemination and resistance to therapy; processes significantly driven by the epithelial-to-mesenchymal transition (EMT). Netrin-1 is a key regulator for EMT. NP137, an anti-netrin-1 antibody, has shown to inhibit EMT in preclinical models and in a phase 1 monotherapy trial. Methods: LAPNET-01 (NCT06203821) is a single arm phase Ib clinical study to assess the combination of NP137 with mFOLFIRINOX in naive locally advanced unresectable PDAC. A safety lead-in (3–12 pts, 3+3 design, NP137 14 vs 9 mg/kg) was followed by a 40-patient expansion. Treatment consisted of NP137 + mFOLFIRINOX every 2 weeks, up to 12 cycles. The primary endpoint was safety at 6 months (all-grade and grade 3/4 adverse events [AEs], CTCAE v5.0). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), surgical conversion rate and exploratory transcriptomic analyses. Laser capture microdissection was performed on 22 pre-treatment and 6 surgery samples to allow microbulk RNA sequencing. Immunohistochemistry was also performed on pre-treatment samples. Results: A total of 43 patients were enrolled in this trial. NP137 was well tolerated. AE occurred in 100% of patients (58% grade ≥ 3). ORR and disease control rate were 29% and 95%. Median PFS was 10.9 months (95% CI, 10.0 – 15.6) and median OS was 16.4 months (95% CI, 12.8 – NR) with 21 patients still alive at time of the data cut-off. Surgery was made possible in 23% of patients. Microbulk RNA sequencing revealed that the main pathway downregulated with the combination mFOLFIRINOX+NP137 is EMT, bringing a clinical validation of the main mechanism of action of NP137. Moreover, patients with tumors expressing high levels of the netrin-1 receptor neogenin (high-NEO1) at baseline (both at the RNA and proteic level (IHC)) demonstrated an improved outcomes compared to the low-NEO1 subgroup including longer median PFS (15.7 vs 10.2 months, p = 0.01) and longer median OS (not reached vs 16.5, p = 0.024). These results are consistent with experimental data demonstrating the implication of NEO1 in PDAC EMT and its progression. Conclusions: NP137 in combination with mFOLFIRINOX demonstrates a favorable safety profile, promising clinical activity and a mechanistically distinct mode of action supported by translational analyses. These results warrant further investigation of netrin-1 blockade in randomized trials and provide a rationale for biomarker-driven development of NP137 in PDAC. Further work is ongoing to better characterize the distribution of NEO1 in first-line unresectable PDAC. Clinical trial information: NCT06203821 .

4104 Background: Nivolumab plus ipilimumab (NIVO + IPI) was globally approved as a first-line (1L) treatment for unresectable hepatocellular carcinoma (HCC) based on the phase 3 CheckMate 9DW trial (NCT04039607). We report 4-year follow-up results and overall survival (OS) by depth of response (DpR). Methods: Methods were reported previously (Yau T. Lancet 2025). Briefly, adults with previously untreated unresectable HCC were randomized 1:1 to receive NIVO + IPI (then NIVO for ≤ 2 years) or lenvatinib/sorafenib (LEN/SOR). OS analyses were done by best percentage change in tumor burden from baseline. We also present exploratory analyses on long-term survivors (survival ≥ 4 years after randomization). Results: A total of 668 patients (pts) were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated with LEN/SOR, 275 (85%) received LEN. At a median (range) follow-up of 52.5 (44.0–66.1) mo, NIVO + IPI continued to show OS benefit (95% CI) vs LEN/SOR (HR 0.78 [0.65–0.93]) with higher objective response rate (ORR; 95% CI) by blinded independent central review (BICR; 36% [31–42] vs 13% [10–17]) and more durable responses. Pts with deeper tumor reduction had numerically improved median OS on both NIVO + IPI and LEN/SOR; the trend was more pronounced with NIVO + IPI specifically in pts with tumor shrinkage ≥ 30% (Table). More pts treated with NIVO + IPI (n = 62) were long-term survivors vs pts treated with LEN/SOR (n = 33). In long-term survivors, ORR by BICR was higher with NIVO + IPI vs LEN/SOR (76% vs 24%), with higher rates of complete response (CR; 21% vs 6%; Table); median duration of response was not reached in either group. Among long-term survivors, median (range) treatment-free interval was 23.3 (0.1–56.6) mo with NIVO + IPI and 0.5 (0.1–54.0) mo with LEN/SOR; 26 of 62 (42%) and 2 of 33 (6%) patients, respectively, were off study treatment and remained free from subsequent treatment. Baseline characteristics and incidence of TRAEs in long-term survivors were consistent with all randomized pts. Conclusions: 1L NIVO + IPI continued to show sustained efficacy benefit vs LEN/SOR in unresectable HCC with no new safety concerns at the 4-year follow-up. These analyses suggest deeper responses with NIVO + IPI may be associated with improved survival outcomes. Long-term survivors treated with NIVO + IPI had higher ORR and CR rates vs LEN/SOR, and were more likely to remain free of subsequent treatment. These results reinforce NIVO + IPI as a 1L treatment for unresectable HCC. Clinical trial information: NCT04039607 . DpR, a % NIVO + IPI(n = 290) b LEN/SOR(n = 286) b Median OS (95% CI), mo Median OS (95% CI), mo −100 to ≤−60 NR (NE) NR (28.3–NE) −60 to ≤−30 31.1 (19.9–40.4) 20.9 (15.1–30.9) −30 to 20 17.0 (14.8–22.0) 20.5 (17.1–22.9) ≥20 14.3 (6.0–17.5) 7.8 (4.8–19.3) Best overall response in long-term survivors a NIVO + IPI (n = 62) LEN/SOR (n = 33) ORR (95% CI), % 76 (63–86) 24 (11–42) CR, % 21 6 a By BICR. b Response evaluable pts. NE, not estimable; NR, not reached.

Netrin1, a developmental cue, is a master regulator of tumour epithelial-to-mesenchymal transition (EMT)1, a mechanism that is known to drive resistance to chemotherapy2. A netrin1 antibody (NP137)3 has been shown to inhibit tumour EMT in preclinical1 and clinical4 settings. In animal models of pancreatic cancer, netrin1 and its receptor neogenin have been shown to promote tumour progression5, EMT5 and metastasis6. Here we report the results of a phase 1b study that assesses the combination of NP137 with modified FOLFIRINOX (mFOLFIRINOX) in first line patients with locally advanced pancreatic cancer (ClinicalTrials.gov: NCT05546853 ). Forty-three patients were enrolled and received mFOLFIRINOX plus NP137 every other week for up to 12 cycles. NP137 was well tolerated. Median progression-free survival (PFS) was 10.85 months (95% confidence interval, 10.03-15.61) and median overall survival was 16.43 months (95% confidence interval, 12.75-non-reached), with 21 patients remaining alive at the time of data cut-off. Post-therapy conversion surgery occurred in 23% of patients. Laser capture microdissection was performed on pre-therapeutic biopsies and surgical specimens. Microbulk RNA sequencing confirmed that the main pathway that was down-regulated with the combination of mFOLFIRINOX plus NP137 was EMT. Moreover, survival outcomes were extended for patients with tumour cells that expressed high levels of the netrin1 receptor neogenin-median PFS 15.65 months in neogenin-high versus 10.22 months in neogenin low. Our results support the idea that netrin1 blockade alleviates resistance to chemotherapy by inhibiting EMT, particularly in neogenin-high pancreatic cancer.

Introduction Les données épidémiologiques françaises de référence englobent tous les cancers primitifs du foie ne distinguant pas le principal type qui est le carcinome hépatocellulaire (CHC) et reposent sur des données ne couvrant pas l’ensemble du territoire (zone registres). Objectif : décrire l’épidémiologie du CHC selon le sexe, dans une cohorte française représentative. Méthodes Les cas de CHC (tous âges) ont été identifiés par le code CIM-10 C22.0 dans l’échantillon représentatif à 2% du Système National des Données de Santé (ESND) entre 2015 et 2021. Les taux d’incidence, prévalence et de mortalité ont été calculés selon le sexe (référence : population totale ESND) et extrapolés à l’échelle nationale (données INSEE). Les méthodes de survie utilisées étaient : Kaplan–Meier et modèle de Cox. Résultats Au total, 246 femmes et 961 hommes ont été inclus. En 2021, l’incidence du CHC était de 20,4/100000PA chez les hommes et 4,5/100000PA chez les femmes (soit 6654 nouveaux cas chez les hommes, 1575 chez les femmes en France). La prévalence était de 67,7/100000PA chez les hommes et 14,6/100000PA chez les femmes (soit 22083 cas chez les hommes, 5079 chez les femmes en France) (augmentation significative par rapport à 2015). La mortalité était de 8,1/100000PA chez les hommes et 2/100000PA chez les femmes (soit 2662 décès chez les hommes, 696 chez les femmes). Les rapports de risque femmes/hommes étaient RRF/H=0.22 (p<0.001), RRF/H=0.21 (p<0.001) et RRF/H=0.25 (p<0.00) respectivement pour l’incidence, la prévalence et la mortalité. Ces écarts tendaient à croître depuis 2015 (incidence : RRF/H=0.31, p<0.001, prévalence : RRF/H=0.25, p<0.001).La survie à 2 ans était de 31% chez les femmes et 37% chez les hommes (p log-rank=0.01). Cette différence était observée uniquement après 65 ans, et s’expliquait par l’âge, l’alcool et le tabac. Discussion/Conclusion Cette étude représentative, précise les disparités épidémiologiques selon le sexe concernant le CHC en France, invitant à mieux comprendre les mécanismes biologiques /comportementaux sous-jacents afin de promouvoir un dépistage plus précoce et une prise en charge équitable

Background & Aims Unresectable hepatocellular carcinoma (HCC) remains a major global health burden. Immunotherapy-based combinations have become the standard of care in first-line (1L) treatment, but evidence on subsequent therapies is limited. We aim at describing access to and outcomes of second-line (2L) treatments following atezolizumab–bevacizumab (AB) compared with sorafenib (Sor), using real-world data from the prospective, French CHIEF cohort. Methods Patients were included in the CHIEF cohort, part of the prospective, real-world STRETCH study (Systemic TReatment sEquences in paTients with unresectable HCC). Adults with unresectable HCC who received 1L treatment with AB or Sor between September 2019 and September 2024 were analyzed. Median overall survival (mOS) and median progression-free survival were calculated from 2L treatment initiation. Results Among 1,103 patients included (AB, n = 899; Sor, n = 204), baseline characteristics were broadly similar, with most patients having Child-Pugh A liver function (77.1% vs. 70.3%) and Barcelona Clinic Liver Cancer stage C disease (66.3% vs. 84.3%). The mOS was 22.3 (95% CI 18.5–27.4) months with AB and 9.4 (7.3–12.7) months with Sor (p <0.0001). After progression, 42.1% of AB-treated and 60.0% of Sor-treated patients received 2L treatment (p <0.001). After AB, 70.8% received tyrosine kinase inhibitors (TKIs) with mOS of 13.0 (9.8–15.5) months; patients receiving immunotherapy or combination regimens did not reach survival (p = 0.0009). The mOS with 2L TKIs was similar after AB or Sor (13.0 vs. 8.6 months; p = 0.082). Conclusions In this prospective real-world cohort, access to 2L treatment was lower after AB than after Sor. Nonetheless, 2L TKIs achieved numerically similar survival outcomes irrespective of 1L therapy, whereas immunotherapy rechallenge yielded encouraging results in selected patients. Impact and implications The increasing use of immunotherapy-based combinations in first-line treatment for unresectable hepatocellular carcinoma raises crucial questions about optimal sequencing strategies after progression. In this study, we provide prospective, real-world evidence on second-line treatment access and outcomes in the post-immunotherapy setting. These findings are important for clinicians and researchers seeking to refine treatment algorithms and ensure equitable access to effective therapies. In practice, the numerically similar survival achieved with tyrosine kinase inhibitors across treatment sequences and the promising results of immunotherapy rechallenge may inform individualized patient management and guide the design of future clinical trials evaluating sequential strategies.

BACKGROUND:The burden of hepatocellular carcinoma (HCC) increases worldwide. We report the current landscape of HCC, in France. METHODS:Carcinome HépatocellulaIrE en France (CHIEF) is a national, prospective, observational cohort initiated in 2019 with the aim of including 5000 patients with HCC, with a 5-year follow-up for each. CHIEF Epidemio 2000, is the first global analysis. RESULTS:In September 2021, 2043 patients were included in 32 centers. We analyzed 1640 patients, 86% men, 68-year-old, BMI 26.8. 70.8% of patients had cirrhosis (MELD score 9, Child-Pugh A in 77.8%, and portal hypertension in 39%. Liver disease was related to alcohol 58.5%, metabolic syndrome 39%, and virus 23.3%. HCC was confirmed by histology in 46.3%. The Milan criteria fulfilled 32.9%, median AFP 39 ng/ml, 5.9% portal thrombosis, and 10.7% metastases. BCLC classes 0, A, B, C, and D were 6.1, 29.8, 28.8, 32.1, and 3.2%, respectively. HCC was detected during a surveillance program in 35.2% associated with better survival (P < 0.001). Median follow-up was 17.76 months (29.1% deaths). The 6, 12, and 18 months overall survival rates were 84.9% (95% CI: 82.8-87), 76.7% (95% CI: 74.2-79.2), 69.3% (95% CI: 66.4-72.3). One-year survival for BCLC 0, A, B, C, and D was at 95.6, 89.7, 81.7, 54.9, and 40%, respectively (P < 0.0001). First-line treatment was curative, locoregional, or systemic in 40.5, 36.2, and 19.2%, with 1-year survival at 92.9, 82.2, and 57.8%, respectively (P < 0.0001). Atezolizumab-bevacizumab yielded a median overall survival of 17.05 months versus nine for TKI (P < 0.0001). CONCLUSION:In real-life data, metabolic syndrome becomes the second cause of HCC in France. The 1-year survival rates are high for all treatments applied, and Immunotherapy yields similar results than in trials.