Liver replacement for alpha₁-antitrypsin deficiency

A 16-year-old girl with advanced cirrhosis and severe alpha₁-antitrypsin deficiency of the homozygous Pi^ZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal Pi^MM phenotype, the alpha₁-antitrypsin concentration in the recipient's serum rose to normal; it had the Pi^MM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous Pi^MZ donor was followed by the identification of that phenotype in the recipient's serum. Neither liver graft developed the alpha₁-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic-based inborn error of metabolism is metabolically cured by liver replacement.