IMAT-HCC model: Liver stiffness-enhanced integrated risk stratification for HCC recurrence after resection.

BACKGROUND &

aimsEarly enthusiasm for adjuvant immunotherapy with atezolizumab plus bevacizumab after curative treatment of hepatocellular carcinoma (HCC) has been tempered by longer follow-up, which questioned the durability of benefit. Beyond treatment efficacy, inadequate patient selection may have contributed. We aimed to externally validate the high-risk criteria adopted in the IMbrave050 trial and to investigate whether integrating liver stiffness measurement (LSM) could improve recurrence risk stratification and provide a pragmatic framework for future adjuvant trial enrolment.

methodsWe retrospectively analysed 147 patients who underwent curative liver resection for HCC between 2010 and 2020 at our institution. High-risk status was defined by IMbrave050 criteria. LSM was assessed preoperatively. Competing-risk analyses (Fine-Gray) evaluated predictors of recurrence and liver-related outcomes; we quantified the added value of LSM using category-based net reclassification improvement. We then defined an integrated selection rule (Integrated Model for Adjuvant Trial Selection in Hepatocellular Carcinoma [IMAT-HCC]) as IMbrave050-IN or IMbrave050-OUT with LSM ≥15 kPa.

resultsOver a median 34 months, 88/147 patients (59.9%) recurred. Both IMbrave050 high-risk features and LSM ≥15 kPa were independently associated with recurrence (subhazard ratio [SHR] 1.66, 95% CI 1.09-2.54; and SHR 1.62, 95% CI 1.07-2.47, respectively). Patients classified as IMbrave050-OUT but with LSM ≥15 kPa showed recurrence rates comparable to IMbrave050-IN patients, whereas those with LSM <15 kPa had substantially lower risk. The IMAT-HCC rule provided clearer separation of cumulative incidence functions than IMbrave050 alone and improved patient reclassification (overall net reclassification improvement 8.0%), driven by correct up-classification of patients who eventually recurred.

conclusionIntegrating LSM into tumour-based risk criteria refines identification of biologically high-risk patients after resection and improves exclusion of truly low-risk individuals. IMAT-HCC represents a simple, non-invasive and trial-ready selection rule that may enhance enrichment strategies for future adjuvant trials in HCC. IMPACT AND IMPLICATIONS: This study demonstrates that integrating liver stiffness measurement with tumour-based criteria refines the identification of patients at high biological risk of recurrence after curative resection for hepatocellular carcinoma. By addressing the limitations of purely tumour-centric selection strategies (i.e. IMbrave050 criteria), it highlights the prognostic relevance of the underlying liver disease in shaping post-resection outcomes. Incorporation of this approach into clinical research and trial design could improve risk stratification and patient selection for adjuvant therapies, while avoiding overgeneralisation given the retrospective, single-centre nature of the study.