Liver transplantation in alpha-1-antitrypsin defi ciency
Authors:
S. Fraňková 1; M. Holinka 1,2; J. Šperl 1,3
Authors‘ workplace:
Klinika hepatogastroenterologie, Transplantcentrum, Institut klinické a experimentální medicíny, Praha 2 3. LF UK, Praha 3 1. LF UK, Praha
1
Published in:
Gastroent Hepatol 2024; 78(2): 129-135
Category:
Hepatology
doi:
https://doi.org/10.48095/ccgh2024129
Overview
Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant genetic condition which manifests with lung emphysema at young age and with liver disease. A point mutation in the SERPINA1 gene, which encodes a1-antitrypsin (AAT), causes a defective secondary structure of the protein, which subsequently accumulates in the endoplasmic reticulum of hepatocytes and is not transported into the blood and body fluids. Deficiency of AAT, which inhibits neutrophil elastase in the lung, thus allows proteolytic damage to the connective tissue of the lung, leading to the development of emphysema. Liver disease is caused by the accumulation of the mutant AAT in liver cells, contributing to proteotoxic liver injury that can lead to liver cirrhosis. Liver transplantation (LT) is the only curative method; after LT, the recipient has the phenotype of the donor organ and normal serum AAT concentrations. The indication for LT should be considered in all patients with AATD and end-stage liver disease. The patients should be referred to the transplant centre when severe complications of liver cirrhosis, such as variceal bleeding, ascites, encephalopathy, and hepatorenal syndrome. In patients with hepatocellular carcinoma, LT represents an optimal treatment modality in the case of an early, unresectable tumour. The timing of LT is crucial; LT should be performed before the patient develops life-threatening complications of end-stage liver disease. LT should be considered in patients of Child-Pugh classification B and C and MELD score of 15 points or higher. Survival of patients after LT for AADT is excellent.
Keywords:
alpha-1-antitrypsin – alpha-1-antitrypsin deficiency – liver cirrhosis – end-stage liver disease – hepatocellular carcinoma – live transplantation
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Poděkování
Děkujeme doc. MUDr. Evě Sticové, Ph.D., a doc. MUDr. Ondřeji Fabiánovi, Ph.D., za poskytnutí obrazové dokumentace.
ORCID autorů
S. Fraňková 0000-0002-1462-5920,
M. Holinka 0009-0007-2353-5189,
J. Šperl 0000-0001-8619-2610.
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Paediatric gastroenterology Gastroenterology and hepatology SurgeryArticle was published in
Gastroenterology and Hepatology
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