Associations Between Liver Biomarkers and Clinical Outcomes in Patients With Primary Sclerosing Cholangitis: A Retrospective Real‐World Study

ABSTRACT Background and Aims This retrospective observational study assessed whether liver biomarker levels and their temporal changes can predict clinical outcomes in patients with primary sclerosing cholangitis (PSC). Approach and Results Adults with any cholangitis diagnosis in the TriNetX Dataworks‐USA network during the study period (2011–2021) were identified; those with ≥ 2 PSC‐specific ICD‐10 codes (K83.01; introduced in 2018) ≥ 30 days apart were included ( N = 2373). Excluding 829 patients with clinical outcomes at baseline, a total of 1544 patients were included in the PSC‐related outcome analysis population. Associations between biomarker levels and clinical outcomes were assessed using multivariate Cox regression models, whereas case–control analyses using logistic regression models evaluated associations between percentage change in biomarker levels (baseline to 6–12 months pre‐outcome) and clinical outcomes. Adjusted hazard ratios and odds ratios (aORs) were calculated for quartiles (Q) 2–4 versus Q1 for ALP, ALT, AST and total bilirubin; and for Q1–Q3 versus Q4 for albumin. Some baseline and pre‐outcome biomarker levels were associated with clinical outcomes. However, most significant findings were associations between changes in biomarker levels over time and clinical outcomes (aOR), including increases in ALP (Q4: 2.78) and AST (Q4: 1.70), decreases in albumin (Q1: 2.48; Q2: 1.89) and cirrhosis; increases in ALP (Q4: 11.45) and bilirubin (Q4: 3.30), decreases in albumin (Q1: 5.88) and hepatic decompensation; increases in ALP (Q4: 2.20) and bilirubin (Q2: 0.55; Q3: 0.46), decreases in albumin (Q1: 3.20) and the composite outcome of other or unspecified cirrhosis, liver transplant or death. Conclusions Monitoring temporal changes in routine liver biomarker levels has clinical utility for predicting the risk of PSC‐related clinical outcomes.