ABSTRACT
BACKGROUND: α1-Antitrypsin deficiency (ATD) is the most common genetic cause of liver injury in young children. Asymptomatic hepatitis is observed in most patients. However, the course of liver disease due to ATD is unpredictable, and some children develop liver cirrhosis. Liver transplantation (Ltx) dramatically improves their outcome and in some cases is required in the first years of life. The aim of the study was to evaluate the course of the disease in children with ATD treated with Ltx in a single center. METHODS: We retrospectively reviewed the clinical features (ascites, esophageal varices, esophageal bleeding) and laboratory parameters of liver function in children with ATD who were treated with Ltx. RESULTS: Twenty-two Ltxs were performed in 20 children (13 boys, 7 girls). Median age at transplantation was 12 years (range 0.5 to 17.1). Four children were transplanted in the first 2 years of life and 16 patients were over 7 years old. The indications for Ltx in younger children were progressive cholestasis with coagulopathy and ascites. In older patients, the indications were as follows: liver failure presenting with variceal bleeding in 7 patients, ascites in 5 patients, hypersplenism in all but 1 patient. In the group of children transplanted over 7 years old, the frequency of cholestasis decreased intermittently in the second year of life: 4 patients (25%) compared to 15 patients (94%) and 10 patients (63%) in the neonatal and pretransplant period, respectively. In the group of children transplanted earlier, cholestasis and hepatitis were maintained until Ltx. Of transplanted patients, 50% were malnourished at the transplantation, and 50% were followed for more than 10 years. Five-year post-transplant survival was 100% (n = 14), and 10-year survival was 90%. Two patients died as adults with biliary post-transplant complications and problems with compliance. CONCLUSIONS: Our experience suggests that transient normalization of liver parameters in some patients with ATD do not exclude the liver disease progression to cirrhosis and unfavorable outcome of liver disease in childhood. In our group of patients, median age at transplantation was high compared to other centers. The long-term prognosis in children after transplantation is very good, but early post-transplant complications and probable problems with compliance in young adults may lead to graft failure.
Subject(s)
Liver Failure/surgery , Liver Transplantation/methods , alpha 1-Antitrypsin Deficiency/surgery , Adolescent , Child , Child, Preschool , Cholestasis/etiology , Cholestasis/surgery , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/etiology , Graft Survival , Humans , Hypersplenism/etiology , Infant , Liver Failure/etiology , Male , Poland , Prognosis , Retrospective Studies , alpha 1-Antitrypsin Deficiency/complicationsABSTRACT
Alpha1-antitrypsin deficiency (alpha1-ATD) is a genetic disorder that may predispose to chronic liver disease. The clinical manifestations and prognosis of this disorder are variable. The aim of the study was to evaluate the clinical presentation and liver tests in two groups of children with alpha1-ATD: those with a good prognosis who survived long term with their native liver, and those with a bad one, requiring liver transplantation (OLT) or dying before OLT. We studied 59 children homozygous for alpha1-ATD admitted to our hospital with cholestasis or chronic hepatitis since infancy. Patients without liver transplantation were regarded to be the good prognosis group I (n=45). In contrast the 11 children who required liver transplantation and the three who died before OLT were the bad prognosis cohort (Group II, n=14). We analyzed the laboratory parameters of cholestasis, hepatitis, and liver insufficiency in both groups. In the group with a good prognosis, eight children still suffered from cholestasis at the ages of 9 to 14 years while nine had hepatitis at the ages of 9 to 14 years. We observed a temporarily increased international normalized ratio (1.2 to 1.5) in eight subjects at the ages of 1 month to 17 years, and slight hypoalbuminemia (30 to 35 mg/dL) in nine children at the ages of 1 month to 10 years. OLT was performed in 11 children at the ages of 10 to 17 years. Our center's experience suggested that in the PiZZ patients with portal hypertension, esophageal varices, or deterioration of hepatic function, liver transplantation should not be delayed.
