ArticlePharmacoepidemiology and drug safety2024
Hepatotoxicity Score: A New Method to Adjust for Use of Potentially Hepatotoxic Medications by Chronic Liver Disease Status.
Article in Pharmacoepidemiology and drug safety, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.Cell biology and toxicology · 2026Article
- High-Throughput Screening Using the Self-Controlled Tree-Based Scan Statistic to Identify Medications Associated With Hospitalization for Severe Acute Liver Injury.Pharmacoepidemiology and drug safety · 2025Article
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
backgroundStudies evaluating the hepatic safety of medications have been limited by the inability to control for confounding from receipt of other hepatotoxic drugs.
objectiveThe objective of this study was to develop an index (Hepatotoxicity Score) to adjust for concomitant hepatotoxic medication exposure within pharmacoepidemiology studies.
methodsWe identified 193 medications with ≥ 4 reports of hepatotoxicity and created cohorts of outpatient initiators in the Veterans Health Administration (2000-2021). Exposure occurred from initiation through 30 days after discontinuation or up to 1 year. We measured age-/sex-adjusted rates of hospitalization for severe acute liver injury (ALI) by chronic liver disease (CLD), identified drugs with high rates, and used these rates as weights in the score. To demonstrate real-world use, we calculated the score for proton pump inhibitor (PPI) initiators. We summed the weights of the drugs dispensed within 90 days prior to PPI initiation. Hazard ratios (HRs) of severe ALI (95% confidence intervals) were measured with and without adjustment for Hepatotoxicity Score.
resultsAmong 89 512 PPI initiators with CLD, HRs of severe ALI were higher for lansoprazole (HR = 2.17 [95% CI, 1.24-3.82]), but not pantoprazole (HR = 0.83 [95% CI, 0.61-1.13]), versus omeprazole. Adjustment for Hepatotoxicity Score attenuated HRs of lansoprazole (HR = 1.99 [95% CI, 1.13-3.50]). Among 2 462 414 PPI initiators without CLD, HRs were not significantly higher for lansoprazole (HR = 1.66 [95% CI, 0.99-2.77]) but were significantly lower for pantoprazole (HR = 0.59 [95% CI, 0.37-0.95]), versus omeprazole. Adjustment for Hepatotoxicity Score attenuated HRs of lansoprazole (HR = 1.52 [95% CI, 0.91-2.54]).
conclusionsThe Hepatotoxicity Score provides a tool to adjust for confounding due to concomitant hepatotoxic drug exposure within hepatic safety studies.
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