ArticlePharmacoepidemiology and drug safety2025
High-Throughput Screening Using the Self-Controlled Tree-Based Scan Statistic to Identify Medications Associated With Hospitalization for Severe Acute Liver Injury.
Article in Pharmacoepidemiology and drug safety, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- 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
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6 authors.
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Abstract
backgroundMedications associated with acute liver injury (ALI) are primarily identified by case reports. High-throughput screening of real-world data could be leveraged to detect hepatotoxicity signals.
objectiveTo apply tree-based scan statistics in real-world data to identify drugs associated with hospitalization for severe ALI among patients without liver/biliary disease and with chronic liver disease (CLD).
methodsWe implemented a self-controlled case-crossover design in Veterans Health Administration data (2000-2023) among patients hospitalized for laboratory-confirmed severe ALI. We identified all newly dispensed drugs within 365 days prior to their hospitalization and used conditional Bernoulli tree-based scan statistics to identify potential associations (p < 0.3). We performed analyses separately in patients without liver/biliary disease and with CLD.
resultsAmong 12 860 patients without liver/biliary disease and 17 512 with CLD hospitalized for severe ALI, we evaluated associations with 450 and 543 drugs, respectively. Drugs associated with severe ALI among patients without liver/biliary disease included: acid-suppressives (ranitidine [p < 0.001], omeprazole [p = 0.004]), antiemetics (ondansetron [p < 0.001], promethazine [p = 0.06]), antibiotics (amoxicillin/clavulanate [p = 0.008], ciprofloxacin [p = 0.02], mupirocin [p = 0.032], ethambutol [p = 0.275]), anticoagulants (heparin [p = 0.015]), and chemotherapy (pazopanib [p = 0.275]). Drugs associated with severe ALI among CLD patients were: diuretics (spironolactone, furosemide [both p < 0.001]), antiemetics (ondansetron, metoclopramide, promethazine [all p < 0.001]), appetite stimulants (p < 0.001), analgesics (morphine, oxycodone, fentanyl [all p < 0.001]), chemotherapy (sorafenib [p < 0.001]), antibiotics (ciprofloxacin [p = 0.011], metronidazole [p = 0.020]), antipsychotics (prochlorperazine [p = 0.105]), vitamins (p = 0.134), acid-suppressives (omeprazole [p = 0.164]), and gastrointestinal/liver disease treatments (lactulose, senna, docusate, silicones, antiflatulents [all p < 0.001]; sucralfate [p = 0.005], albumin [p = 0.228]).
conclusionsHigh-throughput screening using tree-based scan statistics detected potentially hepatotoxic drugs for investigation in future pharmacoepidemiology studies.
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