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

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.

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Journal
Hepatology Communications
Published
2026-07-27
DOI
https://doi.org/10.1097/hc9.0000000000001020
Primary Topic
Liver Disease Diagnosis and Treatment
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article
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article

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

Elisa Pose, Fátima Higuera de La Tijera, Ahmad Anouti, Ângelo Mattos et al.
Hepatology Communications
Liver Disease Diagnosis and Treatment
article

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

Elisa Pose, Fátima Higuera de La Tijera, Ahmad Anouti, Ângelo Mattos, Patrick S. Kamath, Hamza Dahshi, Juan Pablo Roblero, Manual Mendizabal, Terry Cheuk‐Fung Yip, Ming‐Hua Zheng, Winston Dunn, Gil F. Salles, Fernando Javier Barreyro, Francisco J Valentin-Cortez, Ezequiel Ridruejo, Jacqueline Córdova, Mirta Peralta, Xiaodong Zhou, Cláudia Alves Couto, Naim Alkhouri, Katrīna Pekarska, Jimmy Che‐To Lai, Mohamed El‐Kassas, Daniela Simian, A Torres, Guilherme Grossi Lopes Cançado, Rita Fernandes, Mohamad Ali Ibrahim, Rakhi Maiwall, Alejandra Mijangos-Trejo, Laura Temperley, N Chavéz-Tapia, Gustavo Ayares, Berta Cuyàs, Grace Lai–Hung Wong, Hyundam Gu, Juan Diego Torres, Ramón Bataller, Johana Acuña, Helena Pinto, V. Valdes, Luis Antonio Diaz, María Poca, Elias D. Rady, David Marti-Aguado, Nathalie Leite, Arun Sanyal, Richard Parker, Prasun K. Jalal, Sheel Patel, José Antonio Velarde-Ruiz Velasco, Graciela Castro-Narro, William Alazawi, Fernando Bessone, Francisco Idalsoaga, Katherine Marrugo, Veeral Ajmera, Pedro Montes, Anand V. Kulkarni, Mohammad Qasim Khan, Sofia Carvalhana, Pamela Gil, Rohit Loomba, Ramagundam Ramyasri, Alceo Galimberti, Roberta Chaves Araujo, Vincent Wai-Sun Wong, Thomas G. Cotter, Wenhao Li, Ashwani K. Singal, Marco Arrese, Richard K. Sterling, Natalia Baeza, Daniza Contreras, Claudia Regina Lopes Cardoso, Juan Pablo Arab, Shiv K. Sarin, Mazen Noureddin, Igor Lima Ferraz, Jordi Gratacós-Ginès, Cristiane Villela-Nogueira
article en

Abstract

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.

Hepatology CommunicationsVol. 10(8)
Universitat Autònoma de Barcelona (ES), Western University (CA), Mayo Clinic (US), University of Lisbon (PT), University of Louisville (US), Pontificia Universidad Católica de Chile (CL), Queen Mary University of London (GB), Chinese University of Hong Kong (HK), National University of Misiones (AR), Baylor College of Medicine (US), Virginia Commonwealth University (US), Universidad de Guadalajara (MX), Wenzhou Medical University (CN), Leeds Teaching Hospitals NHS Trust (GB), London Health Sciences Centre (CA), First Affiliated Hospital of Wenzhou Medical University (CN), Hospital de Sant Pau (ES), Hospital General de México (MX), WinnMed (US), Daniel Alcides Carrión National University (PE), University of California San Diego (US), Irmandade da Santa Casa de Misericórdia de São Paulo (BR), Southwestern Medical Center (US), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX), Hospital Universitario Austral (AR), Hospital Médica Sur (MX), Methodist Hospital (US), Administração Regional de Saúde de Lisboa e Vale do Tejo (PT), Hospital Provincial de Rosario (AR), Hospital General Dr. Manuel Gea Gonzalez (MX), Centro de Investigación Biomédica en Red (ES), Conceptual Mindworks (United States) (US), Hospital Civil de Guadalajara (MX), Institute of Liver and Biliary Sciences (IN), Santa Casa de Misericórdia de Marília (BR), Texas Health Harris Methodist Hospital Fort Worth (US), University of Kansas Medical Center (US), Hospital Muñiz (AR), Hospital Clínico de la Universidad de Chile (CL), Fundación Santa Fe de Bogotá (CO), Hospital das Clínicas da Universidade Federal de Minas Gerais (BR), Instituto Nacional de Diabetes, Endocrinología y Nutrición (DO), Hospital Universitário Clementino Fraga Filho (BR), Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (AR), Hospital de Santa Maria (PT), Clinics Hospital of Ribeirão Preto (BR), INCLIVA Health Research Institute (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Southwestern Medical Center (US), Helwan University (EG), The University of Texas Southwestern Medical Center (US)
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