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

Mark Deneau, Emily Perito, Amanda Ricciuto, Nitika Gupta, Binita M. Kamath, Sirish Palle, Bernadette Vitola, Vratislav Smolka, Federica Ferrari, Achiya Z. Amir, Tamir Miloh, Alexandra Papadopoulou, Parvathi Mohan, Cara Mack, Kaija Leena Kolho, Raffaele Iorio, Wael El-Matary, Veena Venkat, Albert Chan, Lawrence SaubermannPamela L. Valentino, Uzma Shah, Alexander Miethke, Henry Lin, M. K. Jensen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)92-96.e1
JournalJournal of Pediatrics
Volume209
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Fingerprint

Ursodeoxycholic Acid
Sclerosing Cholangitis
gamma-Glutamyltransferase
Pediatrics
Therapeutics
Crohn Disease
Aspartate Aminotransferases
Platelet Count
Bilirubin
Serum Albumin
Liver Transplantation
Pathologic Constriction
Fibrosis
Blood Platelets

Keywords

  • autoimmune
  • cholestasis
  • juvenile
  • surrogate endpoint
  • treatment

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis : Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course. / Deneau, Mark; Perito, Emily; Ricciuto, Amanda; Gupta, Nitika; Kamath, Binita M.; Palle, Sirish; Vitola, Bernadette; Smolka, Vratislav; Ferrari, Federica; Amir, Achiya Z.; Miloh, Tamir; Papadopoulou, Alexandra; Mohan, Parvathi; Mack, Cara; Kolho, Kaija Leena; Iorio, Raffaele; El-Matary, Wael; Venkat, Veena; Chan, Albert; Saubermann, Lawrence; Valentino, Pamela L.; Shah, Uzma; Miethke, Alexander; Lin, Henry; Jensen, M. K.

In: Journal of Pediatrics, Vol. 209, 01.06.2019, p. 92-96.e1.

Research output: Contribution to journalArticle

Deneau, M, Perito, E, Ricciuto, A, Gupta, N, Kamath, BM, Palle, S, Vitola, B, Smolka, V, Ferrari, F, Amir, AZ, Miloh, T, Papadopoulou, A, Mohan, P, Mack, C, Kolho, KL, Iorio, R, El-Matary, W, Venkat, V, Chan, A, Saubermann, L, Valentino, PL, Shah, U, Miethke, A, Lin, H & Jensen, MK 2019, 'Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course', Journal of Pediatrics, vol. 209, pp. 92-96.e1. https://doi.org/10.1016/j.jpeds.2019.01.039
Deneau, Mark ; Perito, Emily ; Ricciuto, Amanda ; Gupta, Nitika ; Kamath, Binita M. ; Palle, Sirish ; Vitola, Bernadette ; Smolka, Vratislav ; Ferrari, Federica ; Amir, Achiya Z. ; Miloh, Tamir ; Papadopoulou, Alexandra ; Mohan, Parvathi ; Mack, Cara ; Kolho, Kaija Leena ; Iorio, Raffaele ; El-Matary, Wael ; Venkat, Veena ; Chan, Albert ; Saubermann, Lawrence ; Valentino, Pamela L. ; Shah, Uzma ; Miethke, Alexander ; Lin, Henry ; Jensen, M. K. / Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis : Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course. In: Journal of Pediatrics. 2019 ; Vol. 209. pp. 92-96.e1.
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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.",
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AU - Perito, Emily

AU - Ricciuto, Amanda

AU - Gupta, Nitika

AU - Kamath, Binita M.

AU - Palle, Sirish

AU - Vitola, Bernadette

AU - Smolka, Vratislav

AU - Ferrari, Federica

AU - Amir, Achiya Z.

AU - Miloh, Tamir

AU - Papadopoulou, Alexandra

AU - Mohan, Parvathi

AU - Mack, Cara

AU - Kolho, Kaija Leena

AU - Iorio, Raffaele

AU - El-Matary, Wael

AU - Venkat, Veena

AU - Chan, Albert

AU - Saubermann, Lawrence

AU - Valentino, Pamela L.

AU - Shah, Uzma

AU - Miethke, Alexander

AU - Lin, Henry

AU - Jensen, M. K.

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N2 - 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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