Heterozygous alpha-i antitrypsin deficiency as a co-factor in the development of chronic liver disease: a review

• Published in: Netherlands journal of medicine Vol. 65; no. 5; pp. 160 - 166
• Main Authors: KOK, K. F, WAHAB, P. J, HOUWEN, R. H. J, DRENTH, J. P. H, DE MAN, R. A, VAN HOEK, B, MEIJER, J. W. R, WILLEKENS, F. L. A, DE VRIES, R. A
• Format: Journal Article
• Language: English
• Published: Alphen aan den Rijn Van zuiden 01.05.2007
• Subjects: alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - diagnosis; alpha 1-Antitrypsin Deficiency - genetics; Biological and medical sciences; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - genetics; Chronic Disease; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Hepatitis C - complications; Heterozygote; Humans; Liver Diseases - etiology; Liver Neoplasms - etiology; Liver Neoplasms - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Tumors; Disease development; liver disease; Chronic disease; Deficiency; Alpha-i-antitrypsin deficiency; Hepatocellular carcinoma; Hepatic disease; Malignant tumor; Review; Heterozygosity; Medicine; Liver cancer; Chronic; Digestive diseases; Genetics; Bibliographic review
• ISSN: 0300-2977

Alpha-I antitrypsin (AIAT) is an acute-phase protein that is produced in liver cells. AIAT 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 AIAT 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 AIAT deficiency can cause neonatal hepatitis; in adults end-stage liver disease, cirrhosis and hepatocellular carcinoma can develop. There are strong arguments to consider heterozygous AIAT deficiency as an important co-factor in the aetiology of chronic liver disease. Studies have shown that AIAT heterozygosity can be considered a modifier for hepatitis C virus, end-stage liver disease, cirrhosis and hepatocellular carcinoma. The accumulation of AIAT 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 AIAT) 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.