作者
Meritxell Ventura-Cots,Josepmaría Argemi,Patricia D. Jones,Carolin Lackner,Mohamed El Hag,Juan G. Abraldes,Edilmar Alvarado,Ana Paula Grotti Clemente,Samhita Ravi,António Alves,Mohamed Alboraie,José Altamirano,Sergio Barace,Francisco Bosques-Padilla,Robert S. Brown,Juan Caballería,Joaquín Cabezas,Sofia Carvalhana,Helena Cortez‐Pinto,A. Pinto da Costa,Delphine Degré,Carlos Fernandez-Carillo,Nathalie Ganne‐Carrié,Guadalupe García‐Tsao,Joan Genescà,John Koskinas,Nicolas Lanthier,Alexandre Louvet,Juan José Lozano,Michael R. Lucey,Steven Masson,Pierre Bauvin,Nahúm Méndez-Sánchez,Rosa Miquel,Christophe Moreno,Taofic Mounajjed,Gemma Òdena,Won Kim,Pau Sancho‐Bru,R. Warren Sands,Justyna Szafranska,Laurine Verset,Bern Schnabl,Christine Sempoux,Vijay H. Shah,Debbie L. Shawcross,Rudolf Stauber,Beate K. Straub,Elizabeth C. Verna,Dina Tiniakos,Eric Trépo,Vı́ctor Vargas,Càndid Villanueva,John T. Woosley,Marianne Ziol,Sebastian Mueller,Peter Stärkel,Ramón Bataller
摘要
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.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.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.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.