Global multicenter validation of noninvasive fibrosis assessment pathways in MetALD and ALD

Gu H.; Díaz L.A.; Baeza N.; Idalsoaga F.; Zhou X.-D.; Zheng M.-H.; Maiwall R.; Sarin S.K.; Kulkarni A.V.; Ramyasri R.; de la Tijera F.H.; Pinto H.C.; Carvalhana S.; Fernandes R.; Khan M.Q.; Alazawi W.; Li W.; Temperley L.; Marti-Aguado D.; Gratacós-Ginès J.; Pose E.; Poca M.; Cuyas B.; Montes P.; Barreyro F.J.; Ayares G.; Yip T.C.-F.; Wong V.W.-S.; Wong G.L.-H.; Lai J.C.-T.; Villela-Nogueira C.; Leite N.; Salles G.F.; Cardoso C.R.L.; Contreras D.; Velarde-Ruiz Velasco J.A.; Galimberti A.; Bessone F.; Valentin-Cortez F.J.; Mijangos-Trejo A.; Chavez-Tapia N.C.; Ridruejo E.; Peralta M.; Roblero J.P.; Simian D.; Gil P.; El-Kassas M.; Mattos A.Z.; Acuña J.; Araujo R.C.; Ferraz I.L.; Marrugo K.; Vera Torres A.; Torres J.D.; Mejía Valdés V.; Córdova J.; Mendizabal M.; Couto C.A.; Cançado G.G.L.; Cotter T.G.; Anouti A.; Rady E.D.; Dahshi H.; Patel S.; Singal A.K.; Pekarska K.; Parker R.; Ibrahim M.A.; Jalal P.K.; Castro-Narro G.; Noureddin M.; Alkhouri N.; Dunn W.; Kamath P.S.; Sanyal A.; Sterling R.K.; Ajmera V.; Loomba R.; Arrese M.; Bataller R.; Arab J.P. · Hepatology Communications (2026) · DOI: 10.1097/hc9.0000000000001020

Resumen

Background: – Noninvasive tests are well validated in metabolic dysfunction–associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test–based clinical care pathways for fibrosis risk stratification in MetALD and ALD. Methods: – This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013–2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC. Results: – Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0–61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD). Conclusions: – In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD. Copyright