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 [].

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 []. 

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) []

Liver transplant is the only curative treatment.





Source: Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder - Journal of Hepatology (journal-of-hepatology.eu)

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