A1AT Liver disease
Normal human A1AT is a 52-kDa glycoprotein of the serpin (serine proteinase inhibitor) family, predominantly produced in the liver and released into the blood. In affected patients, circulating levels of mutant A1AT are ≤15% of normal protein levels. A1ATD is unique in that it is a proteinopathy that impacts the lungs and the liver by different mechanisms [ 9 ]. In the lungs, it is a loss-of-function mutation, where A1AT is an inhibitor of neutrophil elastase. Emphysema results when A1AT is not present to inhibit the serine proteinase, allowing it to freely destroy the lung tissue [ 10 ]. The liver disease associated with A1ATD is a gain-of-toxic function mechanism. The misfolded insoluble globular proteins (ATZ) accumulate in the endoplasmic reticulum (ER), leading to hepatic fibrosis and even hepatocellular carcinoma (HCC) [ 11 ] Liver transplant is the only curative treatment. Source: Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder - Journa...