LIVER-TRANSPLANTATION FOR END-STAGE LIVER-DISEASE ASSOCIATED WITH ALPHA-1-ANTITRYPSIN DEFICIENCY IN CHILDREN - PRETRANSPLANT NATURAL-HISTORY, TIMING AND RESULTS OF TRANSPLANTATION

Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also no t known why only a small proportion of PiZZ individuals progress towar ds cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficienc y, patients are considered candidates for liver transplantation. In th is paper, the natural history of 16 children who underwent liver trans plantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in a ll children by the age of 12 months. In 11 children, jaundice recurred , always with liver function deterioration. Two patients had a histolo gical paucity of interlobular bile ducts and required early transplant ation due to rapid progression of liver failure. At the time of pretra nsplant assessment, all the patients in this study had portal hyperten sion and seven of them had experienced at least one episode of gastroi ntestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficie ncy. Eighteen orthotopic liver transplantations were performed in 16 p atients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up o f 22 months with an excellent quality of life, normal serum alpha-1-an titrypsin levels and without evidence of liver disease recurrence or p ulmonary complications. Liver disease related to alpha-1-antitrypsin d eficiency should be diagnosed early; infants with jaundice persisting after the age of 6 months and older patients, as well as patients who have experienced recurrent jaundice, prolonged prothrombin time and/or development of portal hypertension, should be referred to a transplan t center for assessment. In most cases, liver disease evolves slowly, but liver transplantation should be performed before the onset of poss ible extrahepatic complications. (C) Journal of Hepatology.