Association of liver biomarker values beyond current thresholds and negative clinical outcomes in primary biliary cholangitis: analysis of a real-world healthcare claims database
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: To assess the predictive effect of threshold deviations for multiple liver biomarkers on negative clinical outcomes, including hepatic decompensation, liver transplantation, and death in patients with primary biliary cholangitis (PBC) using longitudinal data from a large administrative claims database. Materials & methods: A time-dependent Cox proportional hazards model with time-dependent covariates assessed time to first occurrence of hospitalization for hepatic decompensation, liver transplantation, or death in patients with PBC in the Optum Clinformatics Data Mart™ database. Separate models analyzed proportion of time outside prespecified biomarker thresholds (defined as multiples of upper limit of normal [ULN] for alkaline phosphatase [ALP], total bilirubin [TB], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]; lower limit of normal for albumin). Another model evaluated both ALP and TB with the lowest relevant threshold applied for each biomarker. Results: Overall, 2402 patients were included; 85.3% were female, mean age was 63.3 years, median follow-up was 2.2 years (interquartile range: 1.1–3.9 years). On average, patients had approximately five reported measurements for each biomarker evaluated. Each 10% increase in time outside thresholds was associated with a 6.5%, 9.2%, 9.9%, 7.3% and 23.3% increase in risk of negative outcomes for ALP, TB, AST, ALT and albumin, respectively. Conclusion: In patients with PBC, values outside predefined thresholds for biomarkers including ALP, TB, AST, ALT and albumin strongly predicted negative clinical outcomes. These findings highlight the importance of managing biomarkers beyond ALP in monitoring and the treatment of patients with PBC.
Plain language summary: How abnormal liver test results are linked to worse health outcomes in patients with primary biliary cholangitis: a study using real-world health data
Why was this study done?
Patients with primary biliary cholangitis are at risk of serious health problems if the disease is not treated properly. Certain abnormal liver test results at diagnosis or shortly after starting treatment can help predict these risks. One key liver test often used is alkaline phosphatase. However, it is not known whether regularly tracking liver tests over time or including tests in addition to alkaline phosphatase (aspartate aminotransferase, alanine aminotransferase, total bilirubin and albumin) can better predict who will develop these serious outcomes.
What did this study look at?
This study used information from health insurance claims to look at whether abnormal liver test results, tracked over time, were linked to negative health problems such as hospitalization for serious liver complications (hepatic decompensation), liver transplantation or death in patients with primary biliary cholangitis.
What were the results?
Patients who spent more time with abnormal liver test values had a greater risk of serious health problems. The longer they spent outside the normal range, the higher the risk of complications.
What do the results mean?
It is important to monitor liver test results over time. In addition to ALP, other tests like aspartate aminotransferase, alanine aminotransferase, total bilirubin and albumin also play an important role in evaluating risk.
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References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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© 2025 Intercept Pharmaceuticals, Inc. This work is licensed under the Creative Commons Attribution 4.0 License
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Received: 15 November 2024
Accepted: 17 October 2025
Published online: 18 November 2025
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Association of liver biomarker values beyond current thresholds and negative clinical outcomes in primary biliary cholangitis: analysis of a real-world healthcare claims database. (2025) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2024-0198
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