Alpha-1 Antitrypsin Deficiency-Associated Liver Disease
In affected individulas retained Z protein in injured cells fails to undergo apoptosis, leading to chronic regeneration signals to hepatocytes with a lesser load of retained Z protein, increasing the risk of liver disease.
Childhood-onset AATD-associated liver disease presents as neonatal cholestasis; liver abnormalities develop in some cases, leading to liver cirrhosis with 2.4% mortality risk.
Adult-onset AATD-associated liver disease presents as cirrhosis and fibrosis, with a prevalence of up to 40% in older individuals who have never smoked and do not have COPD. The risk for HCC is higher among individuals with AATD and PI*ZZ genotype.
Alpha-1 Antitrypsin Deficiency and Lung Disease
Alpha-1 antitrypsin provides more than 90% protection against neutrophil elastase in the lower airways and can cause lung destruction.
Most individuals with severe AATD (~95%) have evidence of bronchiectasis, and some may develop asthma and chronic bronchitis. Smoking is a major factor in exacerbating COPD and respiratory disease in smokers with AATD usually manifests between the ages of 40 and 50 years. PiMZ heterozygotes have a slightly increased risk for COPD if they smoke, but non-smoking PiMZ heterozygotes are not at risk for emphysema.
SERPINA1