Atteinte hépatique du déficit héréditaire en alpha-1-antitrypsine

Apha-1-antitrypsin deficiency is an autosomal recessive genetic disorder seen in all races. The molecular defect is a specific mutation of the SERPINA1 gene leading to synthesis of an abnormal protein (alpha-1-antitrypsin Z) that cannot be secreted and polymerizes in the endoplasmic reticulum of hepatocytes. The inter-individual variability in the responses to intracellular stress induced by the accumulation of abnormal polymers and the mechanisms allowing their degradation is, without doubt, responsible for the different clinical manifestations of the disease. The disease affects the liver where the abnormal protein is synthesized and the lung, which is its place of action. Liver involvement is well recognized in homozygous infants of the phenotype ZZ. In this situation the disease may present a varying picture from neonatal cholestasis (about 15% of neonatal defects) to cirrhosis. However, evolution towards cirrhosis affects less than 3% of infants with the ZZ phenotype and it is preceded in 80% of cases by neonatal cholestasis. In adolescents or adults the manifestations associated with alpha-1-antitrypsin deficiency are usually limited to biochemical abnormalities but may lead to cirrhosis or hepatocellular carcinoma. The hepatic disorder and its complications are treated symptomatically though the pulmonary involvement may benefit from substitution treatment. More specific treatments targeting the molecular and cellular abnormalities are the subject of research.