A1ATD is the leading genetic cause of liver disease among children. It is a protein-folding disorder in which toxic insoluble ATZ proteins aggregate in the ER of hepatocytes leading to inflammation, fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. The absence of the normal A1AT serum protein also predisposes patients to pan lobar emphysema as adults. At this time, the only approved therapy for A1ATD-associated liver disease is orthotopic liver transplantation, which is curative. However, there has been significant recent progress in the development of small molecule therapies with potential both to preserve the native liver and prevent hepatotoxicity.
Keyphrases
- small molecule
- protein protein
- end stage renal disease
- prognostic factors
- ejection fraction
- newly diagnosed
- oxidative stress
- chronic obstructive pulmonary disease
- peritoneal dialysis
- young adults
- amino acid
- gene expression
- liver injury
- lung function
- copy number
- cystic fibrosis
- idiopathic pulmonary fibrosis
- dna methylation
- human health
- pulmonary fibrosis
- patient reported
- endoplasmic reticulum
- liver fibrosis