Liver disease associated with ZZ α1-antitrypsin deficiency and ursodeoxycholic acid therapy in children

OBJECTIVES:: To investigate the effect of ursodeoxycholic acid (UDCA) in children with liver disease associated with ZZ α1-antitrypsin (AAT) deficiency. PATIENTS AND METHODS:: A total of 42 affected children received UDCA (30 mg · kg ^-1 · day ^-1) and underwent clinical and biochemical follow-up at least yearly. RESULTS:: In group 1,22 children whose mean initial γ-glutamyl-transpeptidase (GGT) was 7.4 ×- N normalized serum liver test results after a mean treatment of 2.6 years. In 16 of these children, UDCA was discontinued. Relapse was observed in 11 children, and liver test results returned to normal after UDCA resumption. In the other 5 children, liver test results remained normal during a mean period of 2.5 years. In group 2, 11 children (mean initial GGT 12.8 × N) had improved liver test results after a mean treatment of 2.3 years. In group 3, 9 children (mean initial GGT 33.8 × N) had no liver test result improvement and evolution toward cirrhosis, requiring liver transplantation in 7. Most of the children in group 1 had normal results of clinical examination after UDCA treatment, versus none in group 3 (P ≤ 0.00001). Initial GGT (P ≤ 0.002) and total bilirubin (P ≤ 0.05) levels were significantly lower in group 1 than in group 3. Combined initial values of GGT ≤ 5.5 × N and total bilirubin ≤ 66 μ mol/L were associated with normalization of liver test results in 90% of children. CONCLUSIONS:: UDCA maysignificantly improve clinical status and liver test results in some children with liver disease associated with ZZ AAT deficiency. No beneficial effect of UDCA was shown in children with the most severe liver involvement. Initial levels of GGT and total bilirubin may be of prognostic value for therapy effectiveness.