Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

Abstract

BACKGROUND AND AIMS:

Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes.

APPROACH AND RESULTS:

We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis.

CONCLUSIONS:

We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

• Authors: Mark R Deneau, Cara Mack, Douglas Mogul, Emily R Perito, Pamela L Valentino, Achiya Z Amir, Matthew DiGuglielmo, Laura G Draijer, Wael El-Matary, Katryn N Furuya, Nitika Gupta, Jessica T Hochberg, Simon Horslen, M Kyle Jensen, Maureen M Jonas, Nanda Kerkar, Bart G P Koot, Trevor J Laborda, Christine K Lee, Kathleen M Loomes, Mercedes Martinez, Alexander Miethke, Tamir Miloh, Saeed Mohammad, Nadia Ovchinsky, Girish Rao, Amanda Ricciuto, Pushpa Sathya, Kathleen B Schwarz, Uzma Shah, Ruchi Singh, Bernadette Vitola, Andréanne Zizzo, Stephen L Guthery
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 73 Issue 3 Pg. 1061-1073 (03 2021) ISSN: 1527-3350 [Electronic] United States
• PMID: 32946600 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Association for the Study of Liver Diseases.

Chemical References

• Serum Albumin
• Vancomycin
• Ursodeoxycholic Acid
• Bilirubin

Topics

• Administration, Oral
• Adolescent
• Bilirubin (blood)
• Child
• Cholangitis, Sclerosing (drug therapy)
• Female
• Humans
• Male
• Propensity Score
• Retrospective Studies
• Serum Albumin (analysis)
• Treatment Outcome
• Ursodeoxycholic Acid (administration & dosage, therapeutic use)
• Vancomycin (administration & dosage, therapeutic use)