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General Principles ⬇

  • α1-Antitrypsin (α1AT) deficiency is an autosomal recessive disease associated with accumulation of misfolded α1AT in the endoplasmic reticulum of hepatocytes.
  • The most common allele is protease inhibitor M (PiM—normal), followed by PiS and PiZ (deficient variants). African Americans have a lower frequency of these alleles.
  • The most prevalent deficiency alleles Z and S are derived from European ancestry.20
  • α1AT deficiency can also be associated with emphysema in early adulthood, as well as other extrahepatic manifestations including panniculitis, pancreatic fibrosis, and membranoproliferative glomerulonephritis.

Diagnosis ⬆ ⬇

Clinical Presentation

  • The disease may present as neonatal cholestasis or, later in life, as chronic hepatitis, cirrhosis, or HCC.
  • The presence of significant pulmonary and hepatic disease in the same patient is rare (1%–2%).

Diagnostic Testing

  • Low serum α1AT level (10%–15% of normal) will flatten the α1-globulin curve on serum electrophoresis.
  • Deficient α1AT phenotype (PiSS, PiSZ, and PiZZ).
  • Elevated AST and ALT.

Diagnostic Procedures

Liver biopsy shows characteristic periodic acid–Schiff-positive diastase-resistant globules in the periportal hepatocytes.

Treatment ⬆ ⬇

Currently, there is no specific medical treatment for liver disease associated with α1AT deficiency. Gene therapy for α1AT deficiency is a potential future alternative.

Surgical Management

Liver transplantation is an option for those with cirrhosis and is curative, with survival rates of 90% at 1 year and 80% at 5 years.

Information ⬆

α1-Antitrypsin Deficiency

Outcome and Prognosis

  • Chronic hepatitis, cirrhosis, or HCC may develop in 10%–15% of patients with the PiZZ phenotype during the first 20 years of life.
  • Controversy exists as to whether liver disease develops in heterozygotes (PiMZ, PiSZ, PiFZ).