Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.
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Ventura-Cots Meritxell, Argemi Josepmaria, Jones Patricia D, Lackner Carolin, El Hag Mohamed, Abraldes Juan G, Alvarado Edilmar, Clemente Ana, Ravi Samhita, Alves Antonio, Alboraie Mohamed, Altamirano Jose, Barace Sergio, Bosques Francisco, Brown Robert, Caballeria Juan, Cabezas Joaquin, Carvalhana Sofia, Cortez-Pinto Helena, Costa Adilia, Degré Delphine, Fernandez-Carrillo Carlos, Ganne-Carrie Nathalie, Garcia-Tsao Guadalupe, Genesca Joan, Koskinas John, Lanthier Nicolas, Louvet Alexandre, Lozano Juan José, Lucey Michael R, Masson Steven, Mathurin Philippe, Mendez-Sanchez Nahum, Miquel Rosa, Moreno Christophe, Mounajjed Taofic, Odena Gemma, Kim Won, Sancho-Bru Pau, Warren Sands R, Szafranska Justyna, Verset Laurine, Schnabl Bern, Sempoux Christine, Shah Vijay, Shawcross Debbie Lindsay, Stauber Rudolf E, Straub Beate K, Verna Elizabeth, Tiniakos Dina, Trépo Eric, Vargas Victor, Villanueva Càndid, Woosley John T, Ziol Marianne, Mueller Sebastian, Stärkel Peter, Bataller Ramon
Аннотация
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.