Association Between Elevated Alkaline Phosphatase and Healthcare Utilization and Costs Among Individuals with Primary Biliary Cholangitis in the United States

Summary for Medical Professionals

 Authors: Robert G. Gish¹, Michel H. Mendler², Edward A. Mena², Chong Kim³, C. Fiorella Murillo Perez³, Yi Pan⁴, Mihail Samnaliev⁴, Diane Ito⁴, Maria Agapova³
Institutions: ¹Robert G. Gish Consultants LLC, San Diego, CA; ²California Liver Research Institute, Pasadena, CA; ³Gilead Sciences, Foster City, CA; ⁴Stratevi, Santa Monica, CA

Presented at: International Society for Pharmacoeconomics and Outcomes Research (ISPOR) — May 13–16, 2025, Montreal, QC, Canada.

Background

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct injury leading to cholestasis, fibrosis, cirrhosis, and potential liver failure.
Prior studies have shown that PBC is associated with substantial clinical and economic burden, yet the relationship between alkaline phosphatase (ALP) — a key biochemical marker of cholestasis — and healthcare resource utilization (HCRU) and costs has not been well defined

This study examined the association between elevated ALP levels and healthcare use and costs using a large, national real-world dataset of individuals with PBC across the United States.

Objective

To assess how increasing ALP levels correlate with healthcare resource utilization and annual healthcare costs among U.S. patients diagnosed with PBC.

Methods

A retrospective longitudinal cohort study was conducted using the Komodo Healthcare Map database, linking national administrative claims and Quest Diagnostics laboratory data from September 2017 through September 2023.

Inclusion Criteria:

  • ≥2 ALP tests ≥30 days apart (index = second ALP test)

  • ≥1 PBC diagnosis during 12 months pre- or post-index

  • ≥12 months of continuous insurance coverage pre- and post-index

  • Age ≥18 years

Patients were categorized into four mutually exclusive ALP cohorts based on Quest Diagnostics reference ranges:

  • Normal: ≤1× upper limit of normal (ULN)

  • Mildly elevated: >1× to ≤1.67× ULN

  • Elevated: >1.67× to ≤3× ULN

  • Highly elevated: >3× ULN

Analyses:

  • Negative binomial regression estimated rate ratios (RRs) for HCRU.

  • Linear regression estimated incremental 1-year cost differences.

  • Models adjusted for demographics, comorbidities, bilirubin, and PBC-related treatments

Results

Cohort Overview

  • Total patients: 10,933 with PBC met inclusion criteria.

  • Demographics: Median age 66 years; 86% female; 60% with Charlson Comorbidity Index ≥2.

  • Treatment: Only 51% received PBC-specific prescriptions during baseline; those with highly elevated ALP had the lowest treatment rate

Clinical Associations

  • Higher ALP was significantly associated with greater prevalence of cirrhosis and pruritus.

  • The highly elevated ALP group showed the highest bilirubin (mean 2.6 mg/dL) and lowest rates of UDCA or OCA therapy.

Healthcare Utilization

Compared to patients with normal ALP:

  • Inpatient visits: Increased across mildly, elevated, and highly elevated groups (all p<.001).

  • Emergency visits: Higher in elevated and highly elevated groups (both p<.001).

  • Outpatient and pharmacy utilization: No significant difference across groups

Healthcare Costs

  • Mean 1-year cost (overall): $18,747 ± $48,621.

  • Unadjusted total costs: rose progressively with ALP level — from ~$20K in elevated to ~$40K in highly elevated cohorts.

  • Adjusted incremental costs (vs. normal ALP):

    • Mildly elevated: +$2,128 (NS)

    • Elevated: +$10,289 (p<.001)

    • Highly elevated: +$12,229 (p<.001)

Conclusions

  • Elevated ALP levels were independently associated with significantly higher healthcare utilization and costs among patients with PBC.

  • The highest ALP groups had the greatest medical burden but the lowest treatment rates, underscoring a gap in care.

  • Achieving and maintaining normal ALP levels may not only improve clinical outcomes but also reduce healthcare costs.

  • These findings reinforce ALP as a meaningful target in PBC management and highlight the need for early identification and effective therapy.

Summary for General Visitors

Understanding the Cost of Liver Disease: How One Blood Test Can Predict Medical Burden

Researchers from California Liver Research Institute and partner institutions studied more than 10,000 Americans living with primary biliary cholangitis (PBC) to understand how a common blood test — alkaline phosphatase (ALP) — relates to healthcare use and costs.

Key Findings

  • People with higher ALP levels were more likely to be hospitalized and visit the emergency room.

  • Those with the highest ALP results had twice the yearly healthcare costs compared to those with normal results.

  • Surprisingly, the group with the highest disease activity was least likely to be receiving PBC treatment, suggesting a gap in care.

Why It Matters

ALP is a key marker of how active PBC is in the liver.
These findings show that keeping ALP levels in the normal range can help:

  • Reduce hospital visits and healthcare costs

  • Improve quality of life for patients

  • Guide better treatment decisions for clinicians