Citations 2
Global multicenter validation of noninvasive fibrosis assessment pathways in MetALD and ALD
Gu, Hyundam , Diaz, Luis Antonio, Baeza, Natalia, Idalsoaga, Francisco, Zheng, Ming‐Hua , Maiwall, Rakhi , Sarin, Shiv K., Kulkarni, Anand V., Ramyasri, Ramagundam, Tijera, Fátima Higuera de La, Pinto, Helena , Carvalhana, Sofia, Fernandes, Rita , Khan, Mohammad Qasim , Alazawi, William, Li, Wenhao, Temperley, Laura , Marti-Aguado, David, Gratacós-Ginès, Jordi, Montes, Pedro, Yip, Terry Cheuk‐Fung , Wong, Vincent Wai-Sun, Villela-Nogueira, Cristiane, Leite, Nathalie, Salles, Gil F. , Cardoso, Claudia Regina Lopes, Contreras, Daniza, Galimberti, Alceo, Bessone, Fernando, Valentin-Cortez, Francisco J , Mijangos-Trejo, Alejandra, Chavéz-Tapia, N, Simian, Daniela , Gil, Pamela, Mattos, Ângelo, Acuña, Johana , Araujo, Roberta Chaves, Ferraz, Igor Lima, Marrugo, Katherine, Torres, A , Torres, Juan Diego , Valdes, V., Córdova, Jacqueline, Mendizabal, Manual, Couto, Cláudia Alves , Cotter, Thomas G., Anouti, Ahmad , Rady, Elias D. , Patel, Sheel , Singal, Ashwani K., Parker, Richard, Ibrahim, Mohamad Ali , Jalal, Prasun K., Noureddin, Mazen, Alkhouri, Naim , Kamath, Patrick S. , Sanyal, Arun, Sterling, Richard K., Ajmera, Veeral, Loomba, Rohit, Arrese, Marco, Bataller, Ramón , Arab, Juan Pablo, Jalal, Prasun K , Cuyas, Berta , Cheuk-Fung Yip, Terry , Zheng, Ming-Hua , Díaz, Luis Antonio , Baeza, Natalia , Idalsoaga, Francisco , Zhou, Xiao-Dong , Sarin, Shiv Kumar , Kulkarni, Anand V., Ramyasri, Ramagundam, Carvalhana, Sofia , Alazawi, William , Li, Wenhao , Aguado, David Martí , Gratacós‐Ginès, Jordi , Pose, Elisa , Poca, María , Cuyàs, Berta , Barreyro, Fernando Javier , Ayares, Gustavo , Wong, Vincent Wai‐Sun , Wong, Grace Lai‐Hung , Lai, Jimmy Che‐To , Cardoso, Claudia R.L. , Velasco, J.A. Velarde-Ruiz , Galimberti, Alceo, Bessone, Fernando , Chávez-Tapia, Norberto Carlos , Ridruejo, Ezequiel , Peralta, Mirta , Roblero, Juan Pablo , El‐Kassas, Mohamed , Araújo, Roberta Chaves , Marrugo, Katherine , Mendizabal, Manuel , Cançado, Guilherme Grossi Lopes , Cotter, T G , Dahshi, Hamza , Singal, Ashwani K. , Pekarska, Katrīna , Jalal, Prasun K. , Castro-Narro, Graciela E , Noureddin, Mazen , Dunn, Winston , Sanyal, Arun J. , Sterling, Richard K. , Ajmera, Veeral , Loomba, Rohit , Arrese, Marco , Arab, Juan Pablo
Hepatology Communications | July 28, 2026 | Volume: 10 | Issue: 8 | Pages: No page available
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.
Clinical, histological and molecular profiling of different stages of alcohol-related liver disease
Ventura‐Cots, Meritxell , Argemí, Josepmaria , Jones, Patricia D. , Lackner, Carolin , Hag, Mohamed El , Abraldeṣ, Juan G. , Alvarado, Edilmar, Clemente, Ana , Ravi, Samhita , Altamirano, José , Barace, Sergio , Caballería, Juan , Carvalhana, Sofia , Cortez‐Pinto, Helena , Costa, Adília, Degré, Delphine, Fernández‐Carrillo, Carlos , García–Tsao, Guadalupe , Koskinas, John , Lanthier, Nicolas , Lozano, Juan José , Lucey, Michael R. , Masson, Steven , Mathurin, Philippe, Miquel, Rosa , Moreno, Christophe , Mounajjed, Taofic, Sancho‐Bru, Pau , Sands, R. Warren , Szafranska, Justyna , Verset, Laurine , Schnabl, Bern, Shah, Vijay H. , Shawcross, Debbie L. , Verna, Elizabeth C. , Vargas, Vı́ctor , Woosley, John T. , Mueller, Sebastian , Stärkel, Peter , Mathurin, Philippe , Alboraie, Mohamed , Bosques, Francisco , Lanthier, Nicolas , Louvet, Alexandre , Masson, Steven , Mathurin, Philippe , Sancho-Bru, Pau , Shah, Vijay, Shawcross, Debbie Lindsay , Bataller, Ramon A , Cortez-Pinto, Helena , Vargas, Victor , Ventura Cots, Meritxell , Abraldes, Juan G , Alves, António , Brown, Robert S. , Cabezas, Joaquín , Ganne‐Carrié, Nathalie , Genescà, Joan , Louvet, Alexandre , Méndez‐Sánchez, Nahúm , Òdena, Gemma , Kim, Won Kyum , Schnabl, Bernd , Sempoux, Christine , Stauber, Rudolf E , Straub, Beate Katharina , Tiniakos, Dina , Trépo, Eric , Villanueva, Càndid , Ziol, Marianne
Gut | January 6, 2022 | Volume: 71 | Issue: 9 | Pages: 1856-1866
Objective Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. Design Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. Results Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. Conclusions Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.