Bile Acid Profiles in Primary Sclerosing Cholangitis and their Ability to Predict Hepatic Decompensation

Abstract

Background & Aims

Altered bile acid (BA) homeostasis is an intrinsic facet of cholestic liver diseases, but clinical usefulness of plasma BA assesment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of PSC patients and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. Approach & Results

Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5‐year risk of hepatic decompensation (HD: defined as ascites, variceal hemorrhage or encephalopathy). There were 400 PSC patients and 302 controls in the derivation cohort (Mayo Clinic) and 108 PSC patients in the validation cohort (Norwegian PSC Research Center). PSC patients had increased BA levels, conjugated fraction and primary‐to‐secondary BA ratios relative to controls. UDCA increased total plasma BA level while lowering cholic acid (CA) and chenodeoxycholic acid (CDCA) concentrations. Patients without inflammatory bowel disease (IBD) had primary‐to‐secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine learning model, PSC‐BAP (bile acid profile) score (C‐statistic, 0.95), predicted HD better than individual measures including alkaline phosphatase and performed well in validation (C‐statistic, 0.86). Conclusions

PSC patients demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.