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DOI: 10.1055/s-0044-1801082
Unique histological liver phenotype in children and adults with severe alpha-1 antitrypsin deficiency (Pi*ZZ genotype)
Aims/objectives: Liver disease in severe alpha-1 antitrypsin (AAT) deficiency (Pi*ZZ genotype) displays a biphasic pattern with the first peak in early childhood and the second, adult peak after the age of 40 years. Our aim was to histologically characterize the pediatric and adult liver disease.
Methods: We recruited 67 adults and 48 Pi*ZZ children aged four weeks to 17 years from six countries who underwent a liver biopsy/transplantation. A blind histological scoring was performed by two histopathologists.
Results: Pediatric Pi*ZZ samples originated more often from liver transplantation (64.6 vs. 21.2%, p<.0001) and children displayed significantly higher liver enzymes than adults. Compared to adults, children presented a significantly higher fibrosis stage according to METAVIR (4.0 vs. 2.5, p<.0001). Pi*ZZ adults more frequently had higher liver steatosis, while bile plugs and duct paucity were significantly more common in Pi*ZZ children (bile plugs: 43.8 vs. 10.4%, p<.0001; duct paucity 58.3 vs. 1.5%, p<.0001). No difference in AAT accumulation (Clark) was found. When subdividing the pediatric cohort based on age (<1 year, 1-5 years and 6-17 years), cirrhosis was more common in both older age groups than in younger children (64.7 vs. 75.0 vs. 30.8%, p=.045). There were no differences in liver steatosis, inflammation, or cholestasis parameters, but youngest children displayed less AAT accumulation and less frequently had larger aggregates.
Conclusions: Our study reveals unique histological patterns in Pi*ZZ children and adults thereby providing basis for patient counseling and further mechanistic studies.
Publication History
Article published online:
20 January 2025
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