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

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. [ABSTRACT FROM AUTHOR]