Pi*ZZ-related liver disease in children and adults—narrative review of the typical presentation and management of alpha-1 antitrypsin deficiency

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a genetic disease affecting both children and adults. It is caused by >100 different mutations in SERPINA1, the α1-antitrypsin (AAT) gene. While the lung is the main afflicted organ in adults, the liver can be affected in both children and adults. The classical form of AATD is the homozygous “Pi*Z” mutation (“Pi*ZZ” genotype) which may result mainly in neonatal hepatitis syndrome and in liver fibrosis in later adulthood. This narrative review focusses on the highly heterogeneous Pi*ZZ-related liver disease (LD) in children and adults and the transition of care. While in a minority of children Pi*ZZ-related LD typically presents as neonatal cholestasis which is largely self-limiting, the majority of Pi*ZZ children do not develop clinically relevant LD. In Pi*ZZ adults, around one third develop signs of significant liver fibrosis. Consequently, Pi*ZZ-related LD is a relatively common cause of liver transplantation which is the only available cure yet. Risk factors for accelerated fibrosis progression in adults are male sex, age ≥50 years, alcohol misuse, obesity, diabetes mellitus, or metabolic syndrome while there are no well-established risk factors in children. The workup of LD is similar in both age groups and includes liver biochemistry, ultrasound, and non-invasive assessment of fibrosis (e.g., elastography). Further workup including liver biopsy might become necessary. While no guidelines exist, in our view, children and adults with signs of Pi*ZZ-related LD should be offered referral to a specialized center in order to counsel the patients and their families regarding their risk of Pi*ZZ-related complications, to define the individual monitoring plan, and to evaluate whether a patient qualifies for a novel treatment modality or liver transplant. Moreover, transition from pediatric to adult hepatologic care should be warranted.