Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation.

Autor: Suri A; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Saint Louis University, St Louis, Missouri, USA., Zhang Z; Department of Health and Clinical Outcomes Research AHEAD Institute, Saint Louis University, St Louis, Missouri, USA., Neuschwander-Tetri B; Department of Medicine Division of Gastroenterology, Saint Louis University, St Louis, Missouri, USA., Lomas DA; Department of Medicine Division of Medicine, UCL Respiratory, University College London, London, UK., Heyer-Chauhan N; Department of Medicine UCL Respiratory, University College London, London, UK., Burling K; Department of Medicine Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Loomba R; Department of Internal Medicine Internal Medicine, University of California San Diego, San Diego, California, USA., Brenner DA; Department of Internal Medicine Internal Medicine, University of California San Diego, San Diego, California, USA., Nagy R; Department of Pediatrics Pediatric Clinical Trial Unit, Saint Louis University, St Louis, Missouri, USA., Wilson A; Department of Internal Medicine Internal Medicine, Boston University, Boston, Massachusetts, USA., Carpenter D; Department of Pathology Pathology, Saint Louis University, St Louis, Missouri, USA., Blomenkamp K; Division of Pediatric Gastroenterology, Department of Pediatrics, Saint Louis University, St Louis, Missouri, USA., Teckman J; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Saint Louis University, St Louis, Missouri, USA.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2024 Dec; Vol. 44 (12), pp. 3204-3213. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1111/liv.16094
Abstrakt: Background and Aims: The course of adults with ZZ alpha-1-antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.
Methods: A prospective cohort, including protocol liver biopsies, was enrolled to address these questions.
Results: We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0-6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0-1, 36% Ishak 2-3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.
Conclusion: In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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