Agreement: I AgreeBody: Dear Editor, Strandberg and colleagues’ development and validation of the Cirrhosis Outcome Risk Estimator (CORE) is certainly a timely and important advance for population-level identification of patients at risk of severe liver outcomes. In large Swedish derivation and validation cohorts, the authors show that CORE achieves markedly better discrimination for 10-year major adverse liver outcomes (MALO) than FIB-4 (AUC ≈0.88 vs 0.79) while relying only on routine variables (age, sex, AST, ALT, GGT), making it attractive for primary-care implementation (1) We congratulate the authors and offer focused commentary intended to strengthen the pathway from model publication to safe, equitable clinical use. Initially, CORE addresses a recognised need: current guidance supports simple first-line tests such as FIB-4 for population screening, but FIB-4 was not originally derived to predict long-term clinical events and shows reduced performance when fibrosis prevalence is low (2,3). CORE’s superior AUC and use of routinely available biochemistry therefore have immediate appeal for scalable screening strategies, intuitively. In contrast, important evidence gaps should be prioritised before widespread implementation. Firstly, external validity across populations with different aetiologies. CORE was derived and validated predominantly in Northern European cohorts; populations with higher prevalence of viral hepatitis, different patterns of metabolic risk, or distinct genetic/ethnic backgrounds may show different calibration and discrimination. International external validation (Middle East, Africa, South Asia, Latin America) is essential (1,4,5). Secondly, threshold selection and net benefit. The appropriate CORE cut-point for referral must be set by local decision-curve analysis that explicitly balances specialist capacity, downstream testing (elastography, hepatology referral), and harms from false positives; one size will not fit all. The original decision-curve analyses are a starting point, but country-specific prevalence and resource modelling must inform thresholds (1). Lastly, impact on patient-centred outcomes. Superior discrimination does not automatically translate into improved morbidity, mortality, or cost-effectiveness; prospective implementation studies or pragmatic trials are needed to test whether CORE-guided pathways improve detection of treatable disease and patient outcomes while remaining affordable (3). In addition, practical implementation challenges require workstreams beyond model validation: integration into electronic health records (automated calculation and flagging), laboratory standardisation for AST/ALT/GGT reporting, clinician education on interpreting predicted absolute risk, and linkage pathways (e.g., reflex transient elastography for those above threshold). Experience from other population risk tools (e.g., LiverRisk) demonstrates that even well-performing scores require careful operationalisation to deliver clinical benefit (4). We can put a finger on CORE being a promising advance with clear potential to enhance early detection of clinically important liver disease. To translate promise into practice, we urge rapid international external validation, context-specific threshold setting using decision-curve methods, and prospective studies of implementation impact in regions with high MASLD and mixed viral burdens. Such coordinated effort will ensure that CORE achieves meaningful, equitable improvements in liver health worldwide (1,5). Yours sincerely, Anas Al-Qatefy https://orcid.org/0000-0003-4485-3737 Faculty of Medicine, Mansoura National University References 1. Strandberg R, Åberg F, Asteljoki J V, Luukkonen PK, Salomaa V, Jula A, et al. Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort study. BMJ [Internet]. 2025 Sep 29 [cited 2025 Sep 30];390:e083182. Available from: https://www.bmj.com/content/390/bmj-2024-083182 2. Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatol [Internet]. 2021 Sep 1 [cited 2025 Sep 30];75(3):659–89. Available from: https://pubmed.ncbi.nlm.nih.gov/34166721/ 3. Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology [Internet]. 2019 Apr 1 [cited 2025 Sep 30];156(5):1264-1281.e4. Available from: https://pubmed.ncbi.nlm.nih.gov/30660725/ 4. Serra-Burriel M, Juanola A, Serra-Burriel F, Thiele M, Graupera I, Pose E, et al. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. The Lancet [Internet]. 2023 Sep 16 [cited 2025 Sep 30];402(10406):988–96. Available from: https://pubmed.ncbi.nlm.nih.gov/37572680/ 5. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology [Internet]. 2023 Apr 1 [cited 2025 Sep 30];77(4):1335. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10026948/ No competing Interests: YesThe following competing Interests: Electronic Publication Date: Tuesday, September 30, 2025 - 01:16AI use: Yes I have used AIHighwire Comment Subject: Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort studyAI use details: Few sentences were refined using a manually controlled AI-based language model to optimise academic clarity.Workflow State: ReleasedFull Title: Reassessing the Cirrhosis Outcome Risk Estimator (CORE) as an Alternative to the Fibrosis Index (FIB-4): A Question of Reliability Highwire Comment Response to: Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort studyCheck this box if you would like your letter to appear anonymously:: Last Name: Al-QatefyFirst name and middle initial: AnasEmail: aanwar@std.mansnu.edu.egAddress: Mansoura, EgyptOccupation: ResearcherAffiliation: Faculty of Medicine, Mansoura National UniversityBMJ: Additional Article Info: Rapid responseTwitter: https://x.com/anasalqatefy