Alkaline phosphatase and bilirubin as predictors of long-term outcomes in primary biliary cholangitis: A systematic literature review

Background: This systematic literature review (SLR) aimed to identify real-world studies investigating associations between biomarkers alkaline phosphatase (ALP) and total bilirubin, and long-term clinical and humanistic outcomes in primary biliary cholangitis (PBC).

Methods: Databases (MEDLINE, Embase, CDSR and DARE) were searched in April 2024, supplemented by searches of conference proceedings since 2022, current clinical guidelines and SLR bibliographies. Observational studies reporting univariate or multivariate analyses of associations between ALP and/or bilirubin and clinical or humanistic outcomes in adults with PBC were included. Studies with≤25 patients and selected PBC cohorts were deprioritised. A narrative synthesis of the included studies is presented.

Results: Seventy-eight publications reporting on 73 unique studies were included; 68 studies quantified prognostic effects of serum levels of ALP and/or bilirubin on outcomes, and 11 studies assessed the accuracy of predictive models including ALP and/or bilirubin. Overall, 72.9% (35/48), 91.7% (55/60) and 91.7% (11/12) of prognostic studies reported a significant association (p<0.05) between ALP, bilirubin, or composite measures including ALP and/or bilirubin (e.g. GLOBE), respectively, and long-term outcomes, e.g. overall survival and transplant-free survival. Few studies evaluated the association between ALP and/or bilirubin and fatigue (n=3), pruritus (n=3) or PBC-40 score (n=2).

Conclusion: These results suggest that measures of bilirubin, ALP and composites including ALP and/or bilirubin are effective surrogate markers of clinically- and patient-relevant long-term clinical outcomes in PBC in real-world contexts. More studies reported a significant association with bilirubin than ALP, suggesting bilirubin as a potentially better predictor of long-term clinical outcomes than ALP.

Publication History

Article published online:
20 January 2025