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Alpha1-antitrypsin deficiency-associated liver disease progresses slowly in some children
D Volpert1, J P Molleston, D H Perlmutter
1Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, Missouri 63110, USA.
Insights
Many children with alpha1-antitrypsin (AT) deficiency do not develop severe liver disease. Some individuals with AT deficiency-related cirrhosis or portal hypertension experience a slow-progressing or stable condition, indicating variable disease severity.
Area of Science:
- Hepatology
- Genetics
- Pediatric Gastroenterology
Background:
- Alpha1-antitrypsin (AT) deficiency affects many children, but most do not develop significant liver disease.
- Limited data exist on the long-term liver disease course in AT-deficient children with cirrhosis or portal hypertension.
Purpose of the Study:
- To investigate the natural history of liver disease in children with homozygous PIZZ alpha1-antitrypsin deficiency.
- To identify factors influencing the progression of liver disease in this population.
Main Methods:
- Retrospective review of patients with homozygous PIZZ alpha1-antitrypsin deficiency.
- Analysis of clinical data including diagnosis of cirrhosis and portal hypertension.
Main Results:
- Out of 44 patients, 17 had cirrhosis or portal hypertension.
- Nine patients experienced a prolonged, stable course (≥4 years) with their liver disease.
- Seven patients maintained relatively healthy lives for up to 23 years despite severe liver disease.
Conclusions:
- Liver disease severity in alpha1-antitrypsin deficiency is highly variable.
- Some patients exhibit chronic, slowly progressing, or non-progressing cirrhosis.
- Overall life functioning may predict disease course better than conventional clinical markers.
Background:
A prospective nationwide screening study initiated more than 20 years ago in Sweden has shown that clinically significant liver disease develops in only 10% to 15% of alpha1-antitrypsin (AT)-deficient children. This study provides information about 85% to 90% of those children, many of whom had elevated serum transaminases in infancy but have no evidence of liver injury by age 18 years. However, there is relatively limited information about the course of alpha1-AT-deficient children who have cirrhosis or portal hypertension. Based on several anecdotal experiences, we have been impressed by the relatively slow progression and stable course of the liver disease in some of these children.
Methods:
We reviewed the course of patients with homozygous PIZZ alpha1-antitrypsin deficiency seen at this institution since establishing a patient database 16 years ago.
Results:
Of 44 patients with alpha1-AT deficiency, 17 had cirrhosis, portal hypertension, or both. Nine of the 17 patients with cirrhosis or portal hypertension had a prolonged, relatively uneventful course for at least 4 years after the diagnosis of cirrhosis or portal hypertension. Two of these patients eventually underwent liver transplantation, but seven are leading relatively healthy lives for up to 23 years while carrying a diagnosis of severe alpha1-AT deficiency-associated liver disease. Patients with the prolonged stable course could be distinguished from those with a rapidly progressive course on the basis of overall life functioning but not on the basis of any other more conventional clinical or biochemical criteria.
Conclusions:
These data provide further evidence for the variable severity of liver disease associated with alpha1-AT deficiency and indicate that some patients have chronic, slowly progressing or nonprogressing cirrhosis.