Clinical, histological and molecular profiling of different stages of alcohol-related liver disease
Por:
Ventura-Cots, M, Argemi, J, Jones, PD, Lackner, C, El Hag, M, Abraldes, JG, Alvarado, E, Clemente, A, Ravi, S, Alves, A, Alboraie, M, Altamirano, J, Barace, S, Bosques, F, Brown, R, Caballeria, J, Cabezas, J, Carvalhana, S, Cortez-Pinto, H, Costa, A, Degre, D, Fernandez-Carillo, C, Ganne-Carrie, N, Garcia-Tsao, G, Genesca, J, Koskinas, J, Lanthier, N, Louvet, A, Lozano, JJ, Lucey, MR, Masson, S, Mathurin, P, Mendez-Sanchez, N, Miquel, R, Moreno, C, Mounajjed, T, Odena, G, Kim, W, Sancho-Bru, P, Sands, RW, Szafranska, J, Verset, L, Schnabl, B, Sempoux, C, Shah, VJ, Shawcross, DL, Stauber, RE, Straub, BK, Verna, E, Tiniakos, D, Trepo, E, Vargas, V, Villanueva, C, Woosley, JT, Ziol, M, Mueller, S, Starkel, P, Bataller, R
Publicada:
11 ago 2022
Ahead of Print:
1 ene 2022
Resumen:
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. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Filiaciones:
Ventura-Cots, M:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Autonoma Barcelona, Vall dHebron Inst Res, Hosp Univ Vall dHebron, Liver Unit, Barcelona, Spain
Argemi, J:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Clin Univ Navarra, Liver Unit, Pamplona, Spain
Jones, PD:
Univ Miami, Miller Sch Med, Dept Med, Div Gastroenterol & Hepatol, Miami, FL 33136 USA
Lackner, C:
Med Univ Graz, Inst Pathol, Graz, Austria
El Hag, M:
Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA
Abraldes, JG:
Univ Alberta, Div Gastroenterol, Liver Unit, Edmonton, AB, Canada
Alvarado, E:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Autonomous Univ Barcelona, Hosp Santa Creu & Sant Pau, Hosp Sant Pau Biomed Res Inst IIB Sant Pau, Gastroenterol, Barcelona, Spain
Clemente, A:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
HGU Gregorio Maranon, Liver Unit, Madrid, Spain
HGU Gregorio Maranon, Digest Dept, Madrid, Spain
Ravi, S:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Alves, A:
Univ Lisbon, Hosp Prof Doutor Fernando Fonseca, Dept Pathol, Inst Anat Patol,Fac Med Lisboa, Lisbon, Portugal
Alboraie, M:
Al Azhar Univ, Dept Internal Med, Cairo, Egypt
Altamirano, J:
Hosp Quironsalud Barcelona, Internal Med, Barcelona, Spain
Barace, S:
Univ Navarra, Hepatol Program, Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Bosques, F:
Univ Autonoma Nuevo Leon, Hosp Sant Jose Tecnol Monterrey, Monterrey, Mexico
Brown, R:
Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY USA
Caballeria, J:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Hosp Clin Barcelona, Liver Unit, Barcelona, Catalunya, Spain
Cabezas, J:
Marques Valdecilla Univ Hosp, Valdecilla Res Inst IDIVAL, Gastroenterol & Hepatol Dept, Santander, Spain
Carvalhana, S:
Univ Lisbon, Clin Univ Gastrenterol, Fac Med, Lisbon, Portugal
Cortez-Pinto, H:
Univ Lisbon, Clin Univ Gastrenterol, Fac Med, Lisbon, Portugal
Costa, A:
Univ Lisbon, Hosp Santa Maria, Dept Pathol, Fac Med Lisboa, Lisbon, Portugal
Degre, D:
Hop Univ Paris Seine St Denis, AP HP, Ctr Ressources Biol BB 0033 00027, Brussels, Belgium
Fernandez-Carillo, C:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Hosp Univ Puerta Hierro, Puerta Hierro Hlth Res Inst IDIPHIM, Dept Gastroenterol & Hepatol, Madrid, Spain
Ganne-Carrie, N:
Univ Paris 13, Hop Univ Paris Seine St Denis, AP HP, Liver Unit,INSERM,Sorbonne Paris Cite, Paris, France
Garcia-Tsao, G:
Yale Univ, Sect Digest Dis, New Haven, CT USA
Dept Vet Affairs Connecticut Healthcare, New Haven, CT USA
Genesca, J:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Autonoma Barcelona, Vall dHebron Inst Res, Hosp Univ Vall dHebron, Liver Unit, Barcelona, Spain
Koskinas, J:
Natl & Kapodistrian Univ Athens, Sch Med, Dept Med 2, Athens, Greece
Lanthier, N:
Clin Univ St Luc, Serv Hepatogastroenterol, UCLouvain, Brussels, Belgium
UCLouvain, Inst Rech Expt & Clin, Lab Hepatogastroenterol, Brussels, Belgium
Louvet, A:
Univ Lille, CHU Lille, INSERM, INFINITI Inst Translat Res Inflammat,U1286, F-590000 Lille, France
Lozano, JJ:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Lucey, MR:
Univ Wisconsin, Sch Med & Publ Hlth, Med, Madison, WI USA
Masson, S:
Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England
Mathurin, P:
Univ Lille, CHU Lille, INSERM, INFINITI Inst Translat Res Inflammat,U1286, F-590000 Lille, France
Mendez-Sanchez, N:
Univ Nacl Autonoma Mexico, Liver Res Unit, Medica Clin & Fdn, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Mexico City, DF, Mexico
Miquel, R:
Kings Coll London, Inst Liver Studies, Liver Histopathol Lab, London, England
Moreno, C:
Univ Libre Bruxelles, CUB Hop Erasme, Dept Gastroenterol Hepatopancreatol & Digest Onco, Brussels, Belgium
Univ Libre Bruxelles, Lab Expt Gastroenterol, Brussels, Belgium
Mounajjed, T:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Odena, G:
Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill Sch Med, Chapel Hill, NC 27515 USA
Univ N Carolina, Dept Nutr, Div Gastroenterol & Hepatol, Chapel Hill Sch Med, Chapel Hill, NC 27515 USA
Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill Sch Med, Chapel Hill, NC 27515 USA
Kim, W:
Seoul Natl Univ, Seoul Metropolitan Govt, Dept Internal Med, Div Gastroenterol & Hepatol,Boramae Med Ctr, Seoul, South Korea
Sancho-Bru, P:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Sands, RW:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
Szafranska, J:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona, Spain
Verset, L:
Univ Libre Bruxelles, Dept Pathol, Hop Erasme, Brussels, Belgium
Schnabl, B:
Univ Calif San Diego, Med, La Jolla, CA 92093 USA
Sempoux, C:
Univ Lausanne, Lausanne Univ Hosp, Inst Pathol, Lausanne, Switzerland
Shah, VJ:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Shawcross, DL:
Kings Coll London, Sch Immunol & Microbial Sci, Fac Life Sci & Med, James Black Ctr,Liver Sci, London, England
Stauber, RE:
Med Univ Graz, Dept Internal Med, Graz, Austria
Straub, BK:
Univ Mainz & Heidelberg, Inst Pathol, Mainz, Germany
Verna, E:
Columbia Univ, Med Ctr, Dept Med, Div Digest & Liver Dis,Columbia Coll Phys & Surg, New York, NY USA
Tiniakos, D:
Newcastle Univ, Translat & Clin Res Inst, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
Natl & Kapodistrian Univ Athens, Med Sch, Aretaie Hosp, Dept Pathol, Athens, Greece
Trepo, E:
Univ Libre Bruxelles, CUB Hop Erasme, Dept Gastroenterol Hepatopancreatol & Digest Onco, Brussels, Belgium
Univ Libre Bruxelles, Lab Expt Gastroenterol, Brussels, Belgium
Vargas, V:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Univ Autonoma Barcelona, Vall dHebron Inst Res, Hosp Univ Vall dHebron, Liver Unit, Barcelona, Spain
Villanueva, C:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Autonomous Univ Barcelona, Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Woosley, JT:
Univ N Carolina, Dept Pathol, Chapel Hill, NC 27515 USA
Ziol, M:
Hop Univ Paris Seine St Denis, AP HP, Ctr Ressources Biol BB 0033 00027, Bondy, France
Mueller, S:
Heidelberg Univ, Salem Med Ctr, Heidelberg, Germany
Heidelberg Univ, Alcohol Res Ctr, Heidelberg, Germany
Starkel, P:
Clin Univ St Luc, Serv Hepatogastroenterol, UCLouvain, Brussels, Belgium
Bataller, R:
Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Ctr Liver Dis,Pittsburgh Liver Res Ctr, Pittsburgh, PA 15213 USA
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