P066 Lower serum concentration of sulfated bile acids is associated with Primary Sclerosing Cholangitis Inflammatory Bowel Disease comorbidity and advanced liver fibrosis
Leibovitzh, H.(1);Nayeri, S.(2);Borowski, K.(2);Hernandez-Rocha, C.(1);Lee, S.H.(1);Turpin, W.(1);Stempak, J.(2);Sandhu, I.(2);Milgrom, R.(2);Smith, M.I.(2);Croitoru, K.(1);Hirschfield, G.M.(3);Gulamhusein, A.(3);Silverberg, M.S.(1);
(1)Zane Cohen Centre for Digestive Diseases- Mount Sinai Hospital, Division of Gastroenterology & Hepatology- Temerty Faculty of Medicine- University of Toronto, Toronto, Canada;(2)Zane Cohen Centre for Digestive Diseases- Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute- Sinai Health System, Toronto, Canada;(3)University of Toronto, Toronto Centre for Liver Disease- Division of Gastroenterology and Hepatology, Toronto, Canada;
Background
Primary sclerosing cholangitis associated Inflammatory bowel disease (PSC-IBD) carries significant morbidity risk. Alterations in bile acid profiles has been shown to modulate chronic inflammation in IBD, but data in PSC-IBD comorbidity is scarce. We aimed to assess associations of serum and stool bile acids (BA) with PSC-IBD phenotype versus ulcerative colitis (UC) and the degree of liver fibrosis in PSC-IBD patients
Methods
In this cross-sectional study, bile acids were profiled in 52 PSC-IBD and 50 UC subjects. Quantitation of bile acids was performed by reversed phase ultrahigh performance liquid chromatography/multiple reaction monitoring mass spectrometry with negative ion detection (TMIC, Alberta, CA). After data filtering and normalization, 71 serum and 76 stool BA were available for analysis. Logistic regression was used to assess associations between BA levels and disease phenotype (PSC-IBD versus UC). Among the PSC-IBD group, linear regression was used to assess associations of fibrosis degree (severe (F4) versus no/mild (F0-3) fibrosis, measured by FibroScan®) with BA profile. Age, sex and ursodeoxycholic acid treatment were included as co-variates in all models and alkaline phosphatase (ALP) was added as co-variate for the liver fibrosis analysis. False discovery rate<0.05 was considered significant
Results
PSC-IBD and UC group had similar age and sex distribution. In the multivariable logistic regression, 26 serum BA were significantly associated with PSC-IBD (Figure 1). Decreased concentrations of taurine/glycine-primary BA [odds ratio(OR)=0.97, 95% confidence interval (CI) 0.95-0.99], taurine/glycine-secondary BA [OR=0.98, 95%CI 0.97-0.99] and sulfated-BA [OR=0.96, 95%CI 0.95-0.98], and increased concentrations of conjugated-BA [OR=1.02, 95%CI 1.01-1.03] and glucuronidated-BA [OR=1.06, 95%CI 1.02-1.1] were associated with PSC-IBD phenotype (q<0.05). Decreased sulfated-BA concentrations remained associated with PSC-IBD [OR=0.96, 95%CI 0.94-0.99, q=0.06] even among PSC-IBD subjects with normal ALP<2XULN (n=67). In contrast, stool BA analysis did not show significant associations with PSC-IBD versus UC. Additionally, in the PSC-IBD group, F4 fibrosis degree compared to F0-3 was associated with lower serum concentrations of taurine/glycine- and sulfated-BA, and higher serum concentrations of conjugated-BA (q<0.05)
Conclusion
Decreased concentration of sulfated-BA was associated with PSC-IBD phenotype with and without cholestasis compared to UC group. Lower sulfated-BA concentration was also associated with severe degree of liver fibrosis among PSC-IBD subjects. This inverse relationship between sulfated-BA levels and PSC-IBD and the degree of fibrosis should be further explored in future mechanistic studies