Alpha-1 antitrypsin (A1AT) is an acute-phase protein that
is produced in liver cells. A1AT deficiency is a hereditary
disease which is defined by the hepatic production of an abnormal protein that can not be released into the plasma. This leads to deficiency of plasma A1AT and
subsequently to an impaired protection against proteases, resulting in pulmonary disease. Accumulation of the abnormal protein in hepatocytes can lead to liver damage. Serum level measurement, phenotyping and liver biopsy can be used for establishing the diagnosis.
Homozygous A1AT deficiency can cause neonatal
hepatitis; in adults end-stage liver disease, cirrhosis and
hepatocellular carcinoma can develop. There are strong
arguments to consider heterozygous A1AT deficiency as
an important co-factor in the aetiology of chronic liver
disease. Studies have shown that A1AT heterozygosity can be considered a modifier for hepatitis C virus, end-stage liver disease, cirrhosis and hepatocellular carcinoma. The accumulation of A1AT in the hepatocytes occurs more profoundly in a diseased liver, and as a consequence it affects the natural course of the liver disease. Therapeutic options include augmentation therapy (infusion of purified human plasma A1AT) in pulmonary disease; in end-stage liver disease liver transplantation is an option.
For the future, other interventions such as gene therapy or strategies to inhibit polymerisation are promising.