title: Autophagy in Hepatocytes in Infants With Alpha-1 ATD and Different Liver Disease Outcomes: A Retrospective Analysis.
abstract: It is unclear whether a distinct activity of pathways removing the antitrypsin (AT) protein in Alpha-1-Antitrypsin Deficiency (α1ATD) are associated with an unfavorable predisposition to liver disease in the future. The aim of this study was to determine whether liverspecific activity of AT protein disposal occurs at infancy in α1ATD with PiZZ phenotype (ATZ).
  
  
  
  Liver samples of 17 infants with unfavorable ATZ outcome (Group I, n = 8, median age  = 0.35 year) and good outcome (Group II, n = 9, 0.17 year), and 9 with biliary atresia (BA, median age = 0.17 year) as control, were enrolled. For each subject were investigated autophagy activity by mRNA, protein expression (Calnexin, Beclin-1, p62, and Parkin), and hepatocyte ultrastructure with morphometric analyses.
  
  
  
  No significant differences in gene expression in the liver of infants were found between the 2 ATZ groups. Although a correlation between patients' age and protein expression was observed, the ATZ groups differed Parkin immunohistochemical expression. Moreover, the hepatocytes in ATZ infants with unfavorable outcome were characterized by low Parkin expression and the presence of isolated mitophagosoms and numerous enlarged mitochondria. The mentioned findings differed in patients with BA.
  
  
  
  Thus, mentioned specific features occurring at infancy may suggest association with poor liver outcome. Parkin low expression could have a potential for disease prognosis and treatment; however, further studies in a greater number of patients are needed.
authors.affiliation: *Department of Pathology †Department of Gastroenterology, Hepatology Nutrition Disorders and Paediatrics, The Children's Memorial Health Institute ‡Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Czarnowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bakuła
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Bierła
authors.forename: Justyna
authors.initials: J
authors.lastname: Niderla-Bielińska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sowińska
authors.forename: Bożena
authors.initials: B
authors.lastname: Cukrowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Cielecka-Kuszyk
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
mesh_terms: D001343:Autophagy / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007223:Infant; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein