Hepatotoxicity Score: A New Method to Adjust for Use of Potentially Hepatotoxic Medications by Chronic Liver Disease Status
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Studies evaluating the hepatic safety of medications have been limited by the inability to control for confounding from receipt of other hepatotoxic drugs. OBJECTIVE: The objective of this study was to develop an index (Hepatotoxicity Score) to adjust for concomitant hepatotoxic medication exposure within pharmacoepidemiology studies. METHODS: We 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. RESULTS: Among 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]). CONCLUSIONS: The Hepatotoxicity Score provides a tool to adjust for confounding due to concomitant hepatotoxic drug exposure within hepatic safety studies.
DOI: 10.1002/pds.70069
Institutions: University of Pennsylvania, Yale University, VA Connecticut Healthcare System, London School of Hygiene & Tropical Medicine, Stanford Medicine, Stanford University, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, University of California, Los Angeles, VA Greater Los Angeles Healthcare System, Rutgers, The State University of New Jersey
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,430
Funders: U.S. Department of Veterans Affairs, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1044130170, G1296680368, G1328571290, G1805777700, G2358688911, 2/6 COMpAAAS U01: Observation Study, G4863538964, G5151718256, 1/6 COMpAAAS U24: Coordinating Center, G679121021, G862316082, Alcohol Associated Outcomes Among HIV+/-Aging Veterans, Yale Clinical and Translational Science Award
OpenAlex ID: W4405253571