Mark Deneau1, Emily Perito2, Amanda Ricciuto3, Nitika Gupta4, Binita M Kamath3, Sirish Palle5, Bernadette Vitola6, Vratislav Smolka7, Federica Ferrari8, Achiya Z Amir9, Tamir Miloh10, Alexandra Papadopoulou11, Parvathi Mohan12, Cara Mack13, Kaija-Leena Kolho14, Raffaele Iorio15, Wael El-Matary16, Veena Venkat17, Albert Chan18, Lawrence Saubermann18, Pamela L Valentino19, Uzma Shah20, Alexander Miethke21, Henry Lin22, M K Jensen23. 1. Department of Pediatrics, University of Utah, Salt Lake City, UT. Electronic address: mark.deneau@hsc.utah.edu. 2. Department of Pediatrics, University of California San Francisco, San Francisco, CA. 3. Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 4. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA. 5. Department of Pediatrics, Oklahoma University, Oklahoma City, OK. 6. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI. 7. Department of Pediatrics, Palacky University, Olomouc, Czech Republic. 8. Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza University of Rome, Rome, Italy. 9. Division of Gastroenterology, Liver and Nutrition, The Dana-Dwek Children's Hospital, Tel-Aviv University, Tel Aviv, Israel. 10. Department of Pediatrics, Texas Children's Hospital, Houston, TX. 11. First Pediatric Clinic, University of Athens, Athens, Greece. 12. Department of Gastroenterology, Hepatology, and Nutrition, Children's National Medical Center, Washington, DC. 13. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO. 14. Department of Pediatrics, University of Helsinki, Helsinki, Finland. 15. Department of Pediatrics, University of Naples Federico II, Naples, Italy. 16. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. 17. Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA. 18. Department of Pediatrics, University of Rochester Medical Center, Rochester, NY. 19. Department of Pediatrics, Yale University School of Medicine, New Haven, CT. 20. Department of Pediatrics, Harvard University, Boston, MA. 21. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 22. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA. 23. Department of Pediatrics, University of Utah, Salt Lake City, UT.
Abstract
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.
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.
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