Gastro hep advances · 2026
Bile Acid Profiles Define Disease-Specific Cholestatic States in Primary Sclerosing and Primary Biliary Cholangitis.
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Juran Brian D, McCauley Bryan M, Hu Chang, Ali Ahmad H, Schlicht Erik M, Bianchi Jackie K, Schell Marjana J, Atkinson Elizabeth J, Hov Johannes R, Vesterhus Mette, Rosenberg William, LaRusso Nicholas F, Gores Gregory J, Karlsen Tom H, Lazaridis Konstantinos N
Аннотация
BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic cholestatic liver diseases with overlapping features but distinct biology. While bile acids (BAs) are central to cholestatic pathophysiology, the extent to which circulating BAs define disease-specific states remains unclear.
METHODS: Plasma BA profiling and clinical laboratory tests were performed in patients with PSC (n = 269), PBC (n = 262), and matched controls (n = 269/262), respectively. BA composition, conjugation patterns, and pool characteristics were compared within and across diseases. Associations with hepatic decompensation were evaluated using univariable and exploratory multivariable analyses, including comparison with established prognostic scores.
RESULTS: Both PSC and PBC exhibited elevated total BA levels compared with controls; however, BA composition and conjugation patterns differed between diseases. PSC was characterized by increased BA conjugation fraction and reduced glycine-to-taurine ratios, whereas PBC showed preserved overall conjugation with increased glycine predominance. In PSC, BA composition was further modulated by inflammatory bowel disease and colectomy, with depletion of secondary BA species. Across both diseases, advancing liver disease stage was associated with shifts toward primary and conjugated BA dominance. BA variables and clinical laboratory tests were associated with hepatic decompensation, particularly in PSC. Exploratory multivariable models showed comparable performance of BA-based and clinical laboratory-based models, and their combination did not materially improve prediction.
CONCLUSION: Plasma BA profiles define distinct cholestatic states in PSC and PBC that reflect disease type, intestinal modifiers, and liver disease stage. While BA variables are associated with clinical outcomes, their principal value lies in complementing established clinical laboratory-based assessments rather than improving predictive accuracy.
METHODS: Plasma BA profiling and clinical laboratory tests were performed in patients with PSC (n = 269), PBC (n = 262), and matched controls (n = 269/262), respectively. BA composition, conjugation patterns, and pool characteristics were compared within and across diseases. Associations with hepatic decompensation were evaluated using univariable and exploratory multivariable analyses, including comparison with established prognostic scores.
RESULTS: Both PSC and PBC exhibited elevated total BA levels compared with controls; however, BA composition and conjugation patterns differed between diseases. PSC was characterized by increased BA conjugation fraction and reduced glycine-to-taurine ratios, whereas PBC showed preserved overall conjugation with increased glycine predominance. In PSC, BA composition was further modulated by inflammatory bowel disease and colectomy, with depletion of secondary BA species. Across both diseases, advancing liver disease stage was associated with shifts toward primary and conjugated BA dominance. BA variables and clinical laboratory tests were associated with hepatic decompensation, particularly in PSC. Exploratory multivariable models showed comparable performance of BA-based and clinical laboratory-based models, and their combination did not materially improve prediction.
CONCLUSION: Plasma BA profiles define distinct cholestatic states in PSC and PBC that reflect disease type, intestinal modifiers, and liver disease stage. While BA variables are associated with clinical outcomes, their principal value lies in complementing established clinical laboratory-based assessments rather than improving predictive accuracy.