Drug‐Induced Ductopenia in Two Prospective Registries: Favourable Outcomes and Late Recovery Despite Prolonged Cholestasis

BACKGROUND & AIMS: Drug-induced ductopenia (DID) represents a rare histological phenotype of drug-induced liver injury (DILI), typically associated with prolonged cholestasis and historically linked to poor outcomes. This study aimed to characterize the clinical presentation, histological features and outcomes of DID using data from the two prospective DILI registries. METHODS: Liver biopsy was performed in 298 patients from the Spanish DILI Registry and the LATINDILI Network. Ten cases (3.4%) fulfilled histological criteria for DID, defined as absence of interlobular bile ducts in more than 50% of portal tracts. Clinical characteristics, biochemical parameters, histological features and outcomes were analysed and compared with those of non-ductopenic DILI cases. RESULTS: Patients with DID had a mean age of 47 ± 18 years, and 50% were female. Mixed liver injury predominated (50%). Causative drugs included amoxicillin-clavulanate, ciprofloxacin, carbamazepine, sertraline, ibuprofen, droxicam, captopril, metformin, ticlopidine and stanozolol. All DID cases had jaundice, and rash was more frequent (40%) compared with 9.4% in non-ductopenic DILI patients (p = 0.013). Total bilirubin was significantly higher in DID (median 12 mg/dL vs. 6.6 mg/dL in non-ductopenic DILI patients; p = 0.027). Histology revealed bile duct loss accompanied by cholestasis, portal inflammation, ductular reaction, fibrosis and occasional interface hepatitis. Despite marked cholestasis, no deaths or liver transplantation occurred in DID cases and biochemical recovery was achieved in most patients. Median follow up was 156 and 116 days in patients with DID and non-ductopenic DILI cases, respectively. CONCLUSIONS: DID is an uncommon phenotype of DILI, characterized by marked hyperbilirubinemia and a frequent association with hypersensitivity features. Most cases exhibited moderate liver injury and followed a benign, reversible clinical course, with no reports of poor outcome. However, delayed recovery was observed in a subset of patients.