Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course.

OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.

Clinical spectrum and histopathologic features of chronic hepatitis C infection in children.

OBJECTIVE: To define the natural history and outcomes of children infected with hepatitis C virus (HCV) at birth or in early childhood. STUDY DESIGN: This retrospective, prospective study identified 60 HCV-infected children through a transfusion look-back program (group 1) and by referrals (group 2). Perinatal/transfusion history, clinical course, and laboratory studies were correlated with findings from 42 liver biopsy specimens. RESULTS: Mean age at infection was 7.1 months, and duration of infection 13.4 years. The sources of infection were blood transfusion (68%), perinatal transmission (13%), and both (7%). Most patients were asymptomatic; three referral patients had advanced liver disease at presentation. Mean alanine aminotransferase level was normal in 25%, 1 to 3 times normal in 62%, and greater than 3 times normal in 13%. Liver biopsy specimens showed minimal to mild inflammation in 71%, absent or minimal fibrosis in 88%, and bridging fibrosis in 12%. Age at infection and serum gamma-glutamyltranspeptidase correlated with fibrosis; serum alanine aminotransferase correlated with inflammation unless complicated by comorbidity. Repeat biopsies within 1 to 4 years in four patients showed no significant progression in three and cirrhosis in one. Two patients died after liver transplantation. CONCLUSIONS: Children with chronic HCV infection are generally asymptomatic. By 13 years after infection, 12% of patients had significant fibrosis. Patients enrolled by referral had more severe liver disease than those identified through the look-back program, demonstrating the importance of selection bias in assessing the long-term outcome of HCV infection.