Alpha -1- Antitrypsin Deficiency [Article in English]

Abstract

Alpha-1-antitrypsin (A1AT) deficiency is the commonest genetic cause of liver disease in children and chronic obstructive lung disease in young adult smokers. The pathogenetic mechanisms are completely different. While low serum levels of A1AT cause reduced alveolar elasticity and subsequent emphysema, the liver disease in children with PiZZ phenotype is due to retention of abnormally folded A1AT in the hepatocytes. The symptomatic liver disease, however, develops in only 10-15% of children carrying the PiZZ phenotype and not in PiSS, PiNull and PiSZ phenotypes  during childhood. The affected children have different degrees of severity of the liver involvement; approximately 25% will develop early cirrhosis necessitating liver transplantation, which represents the only effective treatment at present. A1AT deficiency is being increasingly recognised as a cause of liver disease in adults, where even a heterozygous state (PiMZ) may increase risks of developing hepatopathy in presence of other risk factors, such as chronic hepatitis B and C, alcohol abuse, autoimmunity or increased insulin resistance and steatohepatitis.