Dataset Information

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.

SUBMITTER: Deneau MR

PROVIDER: S-EPMC8557636 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Deneau Mark R MR Mack Cara C Mogul Douglas D Perito Emily R ER Valentino Pamela L PL Amir Achiya Z AZ DiGuglielmo Matthew M Draijer Laura G LG El-Matary Wael W Furuya Katryn N KN Gupta Nitika N Hochberg Jessica T JT Horslen Simon S Jensen M Kyle MK Jonas Maureen M MM Kerkar Nanda N Koot Bart G P BGP Laborda Trevor J TJ Lee Christine K CK Loomes Kathleen M KM Martinez Mercedes M Miethke Alexander A Miloh Tamir T Mohammad Saeed S Ovchinsky Nadia N Rao Girish G Ricciuto Amanda A Sathya Pushpa P Schwarz Kathleen B KB Shah Uzma U Singh Ruchi R Vitola Bernadette B Zizzo Andréanne A Guthery Stephen L SL

Hepatology (Baltimore, Md.) 20210301 3

<h4>Background and aims</h4>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.<h4>Approach and results</h4>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 baselin ...[more]

PMID: 32946600

Similar Datasets

Project description:Background & aimsPrimary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease that can lead to end-stage liver disease and cholangiocarcinoma. High-dose ursodeoxycholic acid (hd-UDCA, 28-30 mg/kg/day) was evaluated in a previous multicentre, randomised placebo-controlled trial; however, the study was discontinued early because of increased liver-related serious adverse events (SAEs), despite improvement in serum liver biochemical tests. We investigated longitudinal changes in serum miRNA and cytokine profiles over time among patients treated with either hd-UDCA or placebo in this trial as potential biomarkers for PSC and response to hd-UDCA, as well as to understand the toxicity associated with hd-UDCA treatment.MethodsThirty-eight patients with PSC were enrolled in a multicentred, randomised, double-blinded trial of hd-UDCA vs. placebo.ResultsSignificant alterations in serum miRNA profiles were found over time in both patients treated with hd-UDCA or placebo. Additionally, there were striking differences between miRNA profiles in patients treated with hd-UDCA compared with placebo. In patients treated with placebo, the changes in concentration of serum miRNAs miR-26a, miR-199b-5p, miR-373, and miR-663 suggest alterations of inflammatory and cell proliferative processes consistent with disease progression. However, patients treated with hd-UDCA exhibited a more pronounced differential expression of serum miRNAs, suggesting that hd-UDCA induces significant cellular miRNA changes and tissue injury. Pathway enrichment analysis for UDCA-associated miRNAs suggested unique dysregulation of cell cycle and inflammatory response pathways.ConclusionsPatients with PSC have distinct miRNAs in the serum and bile, although the implications of these unique patterns have not been studied longitudinally or in relation to adverse events related to hd-UDCA. Our study demonstrates marked changes in miRNA serum profiles with hd-UDCA treatment and suggests mechanisms for the increased liver toxicity with therapy.Impact and implicationsUsing serum samples from patients with PSC enrolled in a clinical trial comparing hd-UDCA with placebo, our study found distinct miRNA changes in patients with PSC who are treated with hd-UDCA over a period of time. Our study also noted distinct miRNA patterns in patients who developed SAEs during the study period.

Project description:ObjectivesAtypical ulcerative colitis (UC) presenting reverse gradient colitis, backwash ileitis, or rectal sparing and/or positive atypical antineutrophil cytoplasmic antibody serology is often associated with primary sclerosing cholangitis (PSC) and can be resistant to conventional medical therapies (CMT) for inflammatory bowel diseases. We report short-term and long-term outcomes of oral vancomycin therapy (OVT) in children with atypical UC and confirmed PSC in imaging/biopsy (PSC-UC) or treatment-resistant atypical UC without detectable PSC (aUC-non-PSC).MethodsIn this retrospective real-world observational study from a tertiary paediatric centre in Brisbane, Australia, 44 children with aUC (29 PSC-UC, 15 aUC-non-PSC) received 79 OVT courses between 2014 and 2023. Pre-post-OVT characteristics were compared and relapses/repeated courses were recorded.ResultsPre-OVT, all had active colitis by Paediatric Ulcerative Colitis Activity Index (PUCAI), Feacal Calprotectin (FC) and/or colonoscopy. Post-OVT, PUCAI reduced from 15 (IQR 5-33) to 0 (IQR 0-5); 85% of children with pre-OVT PUCAI ≥10 achieved clinical remission (100% PSC-UC vs 64% aUC-non-PSC, p=0.019). FC reduced from 995 (IQR 319-1825) to 44 (IQR 16-79) µg/g; 83% of children with pre-OVT FC ≥100 µg/g achieved biochemical remission (92% PSC-UC vs 64% aUC-non-PSC, p=0.063). Colonoscopy confirmed Mayo 0 healing in 62% (67% PSC-UC vs 54% aUC-non-PSC, p=0.443) and 46% achieved pan-colonic histological remission (54% PSC-UC vs 31% aUC-non-PSC, p=0.173). All pre-post-OVT changes in these four markers were significant in both groups. After ceasing first OVT, 25/44 relapsed within 8.2 (IQR 1.9-14.5) months. Recommencing OVT regained biomarker remission in 13/25. During 3.8 (IQR 2.0-5.3) years of follow-up, 79 OVT courses in conjunction with CMT maintained deep remission in 67%. Routine stool testing (n=138) detected no vancomycin-resistant Enterococcus (VRE).ConclusionsOVT induced and reinduced remission in children with atypical UC. Relapse often followed ceasing vancomycin, half responded to reinduction. No VRE was developed.

Dataset Information

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

Background and aims

Approach and results

Conclusions

Publications

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

Similar Datasets

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