Importance:
Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed
genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in
children. Although clinical practice guidelines exist for the management of AAT deficiency, especially
with regards to pulmonary involvement, there are no published recommendations that specifically
relate to the management of the liver disease and monitoring for lung disease associated
with this condition, particularly in children.
Objective:
To review the literature on the management of AAT deficiency-associated liver disease in adults and children.
Evidence Review:
A systematic search for articles indexed in PubMed and published was undertaken.
Some earlier selected landmark references were included in the review. Search terms included:
"alpha1-antitrypsin deficiency"; "liver disease"; "end-stage liver disease"; "liver transplantation"
and "preventative management". Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale.
Findings:
Liver complications arising from AAT deficiency result from the accumulation of mutated
AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis,
pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly
variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver
function tests should be obtained to assess for liver involvement; however, the only curative treatment
for AAT deficiency-associated liver disease is organ transplantation.
Conclusion and Relevance:
There should be a greater vigilance for AAT deficiency testing among
pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency-
associated liver disease should be referred to a liver specialist and monitored throughout
their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement.
Alpha1-Antitrypsin Deficiency: Transition of Care for the Child With AAT Deficiency into Adulthood