Liver Fibrosis Assessment in Adults with Alpha1-Antitrypsin Deficiency

Abstract

Alpha1-antitrypsin deficiency is a genetic disorder elicited by mutations in alpha1-antitrypsin (AAT) gene. Among them, a homozygous Pi∗Z mutation (Pi∗ZZ genotype) causes early-onset lung emphysema and liver fibrosis, while heterozygous Pi∗Z carriage (Pi∗MZ genotype) is considered a risk factor for development of liver cirrhosis in patients with nonalcoholic and alcoholic liver disease. In Pi∗ZZ homozygotes, liver disease constitutes the second leading cause of death and 35% of Pi∗ZZ individuals display a histologically proven, significant liver fibrosis (i.e. F ≥ 2). Among, noninvasive methods, liver stiffness measurement (LSM) via transient elastography (TE) has been most extensively evaluated. Based on these data, Pi∗ZZ subjects have a 20× increased risk of developing advanced liver fibrosis (i.e. F ≥ 3) than adults without AAT mutation. Males, individuals ≥50 years old and/or displaying metabolic syndrome carry a particularly high risk. In contrast to TE, other elastography methods have been evaluated only in small studies and further analyses are needed to determine their usefulness. Among blood-based tests, AST-to-platelet ratio index (APRI) is based on routinely available parameters and correlates moderately with LSM. Given its wide availability, it can be used for risk stratification when LSM is not at hand. Despite recent efforts, AATD-related liver disease remains a greatly understudied disease.