α1 Antitrypsin deficiency - liver disease

α1 Antitrypsin deficiency

Definition

Inherited cause of chronic liver disease and panacinar emphysema.

Aetiology

The gene for α1 antitrypsin (Pi, for Protease Inhibitor) is found on chromosome 14. It has more than 30 different alleles which are defined according to their motility on electrophoretic gel. The normal phenotype is designated PiMM. Z is the most abnormal allele, it encodes for a defective protein which cannot be excreted from hepatocytes.

Pathophysiology

α1antitrypsin is an extracellular inhibitor of neutrophil elastase. In its absence, damage to cells is not controlled. Individuals who have a PiMZ phenotype have an increased risk of developing emphysema. Cigarette smoke probably contributes to this by inhibiting any functioning antitrypsin which is present. Those with a ZZ phenotype develop emphysema and cirrhosis.

Clinical features

ZZ homozygotes usually present in the first year of life, with symptoms of neonatal hepatitis, i.e. pale stools, dark urine and an enlarged liver. Occasionally, the individual is asymptomatic until adulthood, when they present with cirrhosis.

Investigations

Liver function tests are abnormal. Liver biopsy shows variable histology including hepatocellular necrosis, inflammation, fibrosis and cirrhosis.α1antitrypsin levels can be measured and are low.

Management

Supportive, patients must not smoke, end-stage liver failure may require liver transplantation.