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

• Published in: Liver international Vol. 44; no. 12; pp. 3204 - 3213
• Main Authors: Suri, Anandini, Zhang, Zidong, Neuschwander‐Tetri, Brent, Lomas, David A., Heyer‐Chauhan, Nina, Burling, Keith, Loomba, Rohit, Brenner, David A., Nagy, Rosemary, Wilson, Andrew, Carpenter, Danielle, Blomenkamp, Keith, Teckman, Jeffrey
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2024
• Subjects: Accumulation; Adult; Adults; Alanine; Alanine transaminase; Alanine Transaminase - blood; alpha 1-Antitrypsin - blood; alpha 1-Antitrypsin - genetics; alpha 1-Antitrypsin Deficiency - blood; alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - diagnosis; alpha 1-Antitrypsin Deficiency - genetics; alpha 1-Antitrypsin Deficiency - pathology; Aspartate aminotransferase; Aspartate Aminotransferases - blood; Biomarkers; Biomarkers - blood; Biopsy; Body Mass Index; Body size; cirrhosis; Consumption patterns; Correlation; Fatty liver; Female; Fibrosis; Glutamine; Histopathology; Humans; Inclusion bodies; Inclusions; Inflammation; Liver; Liver - pathology; Liver Cirrhosis - blood; Liver Cirrhosis - diagnosis; Liver Cirrhosis - etiology; Liver Cirrhosis - pathology; liver disease; Liver diseases; Male; Middle Aged; Necrosis; Obesity; Polymers; Prospective Studies; Protein deficiency; Proteins; Respiratory function; Steatosis; Transaminases; United States; Z polymer; United States; Z polymer; liver disease; cirrhosis; obesity; aspartate aminotransferase
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/liv.16094

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.