• To diagnose alpha-1 antitrypsin deficiency in the appropriate clinical context
  • Initial laboratory test is serum AAT, which is decreased in AAT deficiency (< 1.1 g/L)
  • Correlation with enzyme phenotype (e.g., PiMZ or PiZZ) is recommended to confirm the diagnosis and determine heterozygous versus homozygous deficiency state
  • Note: there is no direct correlation between the serum AAT value, the Pi phenotype and the presence or absence of immunoreactive periportal AAT granules; thus, IHC alone cannot confirm or exclude AAT deficiency (J Clin Pathol 1986;39:58)
• Can be used to study AAT protein expression within the human liver or exogenous AAT that is delivered through gene therapy (Methods Mol Biol 2017;1639:139)

Contributed by Avani Pendse, M.D., Ph.D.

A 38 year old man with clinical concern for early onset liver fibrosis has longstanding mild to moderate elevation in transaminases. Viral hepatitis serology is negative and there is no recent history of medication changes or herbal supplement use. A liver biopsy was performed and showed mild portal inflammation with no significant interface activity. A trichrome stain showed bridging fibrosis. Many hepatocytes showed periodic acid-Schiff diastase (PASD) positive cytoplasmic globules. What is the likely etiology of the patient's liver disease and the confirmatory immunohistochemistry that would aid with diagnosis?

1. Alcohol; glutamine synthetase
2. Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin
3. Autoimmune hepatitis; CD138
4. Steatohepatitis; heat shock protein
5. Viral hepatitis; hepatitis B surface antigen

B. Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin. Answers A, C, D and E are incorrect because although liver fibrosis has a variety of etiologies, intracytoplasmic globules that express alpha-1 antitrypsin in hepatocytes are compatible with alpha-1 antitrypsin deficiency.

Comment Here

Reference: Alpha-1 antitrypsin