Vanishing bile duct syndrome reports and recorded fatal outcomes in FAERS: a disproportionality analysis

Background Vanishing bile duct syndrome (VBDS) is a rare but life-threatening condition characterized by progressive destruction of intrahepatic bile ducts, often leading to cirrhosis and death. Large-scale pharmacovigilance studies systematically investigating VBDS reports, particularly those with reported fatal outcomes, remain scarce. Methods We conducted a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database (2004 Q1–2025 Q4). VBDS reports were identified using the MedDRA preferred term “Vanishing bile duct syndrome” (Code 10054753). We applied four algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). A positive signal required meeting criteria for all four methods simultaneously. For drugs meeting signal criteria, we further performed a two-dimensional cross-analysis by intersecting drugs with the highest total report counts and those with the highest death counts, to identify drugs appearing in both top-10 rankings. Results After deduplication, 19,588,161 unique adverse event reports were available, among which 997 reports coded as VBDS were identified. A death outcome was recorded in 193 reports (19.36%); this proportion reflects FAERS reporting patterns and should not be interpreted as VBDS-attributable mortality or a clinical case-fatality estimate. Disproportionality analysis identified 48 drugs meeting all four signal criteria. Notably, only carbamazepine explicitly mentioned VBDS in its FDA label, and merely 18 of the 48 drugs included the broader term “cholestasis”. Through cross-analysis of total report counts and reported death counts, six drugs appeared in both top-10 ranking lists: ibuprofen, ciprofloxacin, azithromycin, sulfamethoxazole–trimethoprim, avacopan, and celecoxib. Conclusions This large-scale pharmacovigilance analysis of FAERS suggests the mention of VBDS among FDA product labels differs across drugs generating post-marketing safety signals, and that this difference warrants further regulatory and clinical evaluation. Six agents (ibuprofen, ciprofloxacin, azithromycin, sulfamethoxazole-trimethoprim, avacopan, celecoxib) appeared in both top-10 ranking lists for total VBDS reports and reported death counts. Because these rankings are based on descriptive absolute FAERS report counts, these agents warrant further clinical and pharmacovigilance evaluation, particularly in patients with pre-existing risk factors for DILI. These findings may support pharmacovigilance surveillance and hypothesis generation, but should be interpreted as reporting associations rather than the evidence of causality.