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Transplantation for end stage liver disease related to alpha 1 antitrypsin
G Vennarecci1, B K Gunson, T Ismail
1The Liver Unit, The Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
Insights
Alpha 1 antitrypsin deficiency (AT) is a genetic liver disorder. Liver transplantation successfully treats AT deficiency, improving patient outcomes and preventing disease progression.
Area of Science:
- Genetics
- Hepatology
- Transplantation
Background:
- Alpha 1 antitrypsin (AT) deficiency is an inherited disorder causing chronic liver disease in children and adults, and emphysema in adults.
- It is a common genetic disorder in Caucasians and a leading cause for pediatric liver transplants.
- The liver injury's cause and disease progression are not fully understood.
Purpose of the Study:
- To analyze clinical features and outcomes of liver transplantation in patients with Alpha 1 antitrypsin deficiency.
- To correlate pretransplant factors with post-transplant survival.
Main Methods:
- Retrospective analysis of 35 patients (22 adults, 13 children) with Alpha 1 antitrypsin accumulation who underwent liver transplantation.
- Correlation of clinical presentation, phenotype, serum AT levels, and precipitating factors with transplant outcomes.
Main Results:
- Children were PiZZ homozygotes presenting with neonatal hepatitis; adults were mostly heterozygotes with cirrhosis and portal hypertension.
- One-year post-transplant survival rates were 73% for adults and 87.5% for children.
- Liver replacement normalized the donor phenotype and serum AT levels, preventing further disease.
Conclusions:
- Liver transplantation is an effective treatment for Alpha 1 antitrypsin deficiency-related liver disease.
- Transplantation offers good survival rates and prevents disease recurrence.
- Understanding patient phenotypes is crucial for managing this genetic disorder.
Abstract:
Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.