Abstract
BACKGROUND: Non-invasive tests (NITs) are central to diagnosing and stratifying risk in steatotic liver disease (SLD). However, it remains unclear whether guideline-recommended NIT cut-offs apply to metabolic and alcohol-related liver disease (MetALD). AIM: Evaluate the diagnostic and prognostic performance of five NITs in patients with MetALD. METHODS: Single-centre study with 423 SLD patients, of whom 102 (24%) had MetALD. Patients were classified using histological or controlled attenuation parameter-defined hepatic steatosis and self-reported alcohol intake. We assessed the circulating markers of FIB-4, LiverRisk score, ELF and ADAPT together with transient elastography (TE) using established cut-offs for advanced fibrosis (≥ F3). Liver histology served as reference. Prognostic performance for hepatic decompensation and all-cause mortality was evaluated over a median follow-up of 62 months. RESULTS: Among circulating NITs in MetALD, ELF and ADAPT both had the highest diagnostic accuracy (AUROC = 0.90), while it was lowest with LiverRisk score (AUROC = 0.74). The indeterminate zone between rule-out and rule-in cut-offs was largest for FIB-4 (34%). TE and circulating NIT concordance was highest for LiverRisk score (81%) to rule-out ≥ F3, and highest for ELF (88%) to rule-in ≥ F3. All included NITs predicted decompensation-free survival with their corresponding rule-out or rule-in cut-offs. A sequential 2-tier testing strategy (FIB-4 → TE) effectively stratified risk of decompensation. Incorporating a second-tier test (ELF or ADAPT) before TE reduced the number of TE referrals by 43% and 45%, without loss of prognostic performance. CONCLUSION: Widely available NITs are applicable for MetALD, where cut-offs can be used to diagnose advanced fibrosis and predict clinical outcomes.