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The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study.
Madill-Thomsen, Katelynn S; Abouljoud, Marwan; Bhati, Chandra; Ciszek, Michal; Durlik, Magdalena; Feng, Sandy; Foroncewicz, Bartosz; Francis, Iman; Grat, Michal; Jurczyk, Krzysztof; Klintmalm, Goran; Krasnodebski, Maciej; McCaughan, Geoff; Miquel, Rosa; Montano-Loza, Aldo; Moonka, Dilip; Mucha, Krzysztof; Myslak, Marek; Paczek, Leszek; Perkowska-Ptasinska, Agnieszka; Piecha, Grzegorz; Reichman, Trevor; Sanchez-Fueyo, Alberto; Tronina, Olga; Wawrzynowicz-Syczewska, Marta; Wiecek, Andrzej; Zieniewicz, Krzysztof; Halloran, Philip F.
Afiliación
  • Madill-Thomsen KS; Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.
  • Abouljoud M; Henry Ford Hospital, Detroit, Michigan, USA.
  • Bhati C; Virginia Commonwealth University, Richmond, Virginia, USA.
  • Ciszek M; Department of Immunology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
  • Durlik M; Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Feng S; University of California San Francisco, San Francisco, California, USA.
  • Foroncewicz B; Department of Immunology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
  • Francis I; Henry Ford Hospital, Detroit, Michigan, USA.
  • Grat M; Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
  • Jurczyk K; Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland.
  • Klintmalm G; Baylor University Medical Center, Dallas, Texas, USA.
  • Krasnodebski M; Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
  • McCaughan G; Centenary Research Institute, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, The University of Sydney, Sydney, New South Wales, Australia.
  • Miquel R; King's College London, London, UK.
  • Montano-Loza A; University of Alberta, Edmonton, AB, Canada.
  • Moonka D; Henry Ford Hospital, Detroit, Michigan, USA.
  • Mucha K; Department of Immunology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
  • Myslak M; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
  • Paczek L; Department of Clinical Interventions, Department of Nephrology and Kidney Transplantation SPWSZ Hospital, Pomeranian Medical University, Szczecin, Poland.
  • Perkowska-Ptasinska A; Department of Immunology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
  • Piecha G; Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Reichman T; Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland.
  • Sanchez-Fueyo A; Virginia Commonwealth University, Richmond, Virginia, USA.
  • Tronina O; King's College London, London, UK.
  • Wawrzynowicz-Syczewska M; Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
  • Wiecek A; Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland.
  • Zieniewicz K; Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland.
  • Halloran PF; Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
Am J Transplant ; 22(3): 909-926, 2022 03.
Article en En | MEDLINE | ID: mdl-34780106
To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Hígado / Hígado Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Hígado / Hígado Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos