Abstract
BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease frequently associated with inflammatory bowel disease (IBD). PSC-IBD represents a distinct phenotype with extensive colitis, right-sided predominance, and elevated colorectal cancer risk. We aimed to evaluate the impact of oral vancomycin on clinical, endoscopic, and histologic findings of IBD and both intestinal and liver biomarkers of these patients. METHODS: A retrospective study was performed among patients with PSC-IBD treated with oral vancomycin from January 1992 to August 2024. Data collected included demographics, disease characteristics, prior therapies, vancomycin use and dosing, clinical response, laboratory markers, endoscopic, and histologic activity of the colon. Vancomycin-free survival was estimated using Kaplan-Meier analysis. RESULTS: Among 90 patients (80% ulcerative colitis) included, the median age at PSC diagnosis was 17.4 years. Clinical improvement related to intestinal inflammation was observed in 50%, and 12.2% achieved remission. Endoscopic inactivity increased from 18.8% to 60.3%, and histologic inactivity or mild disease rose from 57.7% to 86.2%. Median change in serum alkaline phosphatase was -48.5 U/L (P = .5681), and median fecal calprotectin decreased from 485 μg/g to 67.7 μg/g. Clinical, endoscopic, and biochemical improvements were observed across low- (≤500 mg/d) and high-dose (>500 mg/d) groups. Five-year vancomycin-free survival was comparable between dose groups. CONCLUSION: Oral vancomycin was associated with meaningful improvements in clinical, endoscopic, histologic, and biomarker outcomes in intestinal inflammation of patients with PSC-IBD, with durable responses across different doses. These findings support vancomycin as a potential disease-modifying therapy, warranting prospective randomized trials to establish efficacy, optimal dosing, and long-term safety.