Autophagy in Hepatocytes in Infants with Alpha-1 ATD and Different Liver Disease Outcomes. A Retrospective Analysis.

Objectives: It is unclear whether a distinct activity of pathways removing the AT protein in Alpha-1-Antitrypsin Deficiency ([alpha]1ATD) are associated with an unfavorable predisposition toliver disease in the future. The aim of this study was to determine whether liverspecific activity of AT protein disposal occurs at infancy in [alpha]1ATD with PiZZ phenotype (ATZ). Methods: 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. Results: No significant differences in gene expression in the liver of infants were found between the two 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. Conclusions: 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. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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