Hepatotoxicity Associated with Labetalol Use: A Case Report with Systematic Review and Disproportionality Analysis Using FAERS.

Labetalol is widely prescribed as a first-line antihypertensive in pregnancy; however, rare but potentially severe idiosyncratic hepatotoxicity has been reported, with a disproportionately strong reporting signal for liver injury relative to other β-blockers. In this report, a fatal case is described in which mild initial symptoms rapidly progressed to fulminant hepatocellular injury and acute liver failure within days, underscoring the importance of early recognition of drug-induced liver injury and prompt discontinuation of labetalol. A PRISMA-guided systematic review of MEDLINE, Embase, CINAHL, Cochrane Library, PubMed, and Google Scholar (from inception to December 2025) identified 27 published case reports. Patients were predominantly female (≈80%), and one-third were pregnant or postpartum. Latency ranged from 7 to 365 days (median ≈60 days). The injury phenotype was consistently hepatocellular, often with autoimmune-like serologic or histologic features. Outcomes included full recovery in most (≈75%), but also liver transplantation and death. In the FDA Adverse Event Reporting System (2020Q1-2025Q1), labetalol showed strong disproportionality signals for DILI (PRR 22.7, 95% CI 15.6-33.1; ROR 23.7, 95% CI 16.0-35.1; IC025 2.5) and autoimmune hepatitis (PRR 59.8, 95% CI 34.1-104.8; ROR 60.9, 95% CI 34.4-108.1; IC025 2.8), which persisted when restricted to other β-blockers as comparators. Signals for acute hepatic failure and hyperbilirubinemia were elevated but less statistically robust. The available evidence is consistent with a clinically meaningful and biologically plausible association between labetalol and idiosyncratic hepatotoxicity, supporting heightened clinical awareness and further mechanistic and population-based study.