DRUG-INDUCED DUCTOPENIA IN THE SPANISH AND LATINDILI REGISTRIES

Introduction and Objectives

Ductopenia is a rare phenotype of drug-induced liver injury (DILI), usually emerging after prolonged cholestasis. This study aimed to evaluate the clinical, histological, and outcome features of drug-induced ductopenia (DID) using data from the Spanish and LATINDILI registries.

Materials and Methods

Among 1,564 DILI cases (Spanish: 1,037; LATINDILI: 527), 10 cases met criteria for DID, defined as vanishing interlobular bile ducts in >50% of portal tracts. Clinical, biochemical, and histological data, along with outcomes, were analyzed.

Results

The mean age of DID patients was 50 ± 19 years; 45% were female. Clinical presentation was hepatocellular in 40%, mixed in 40%, and cholestatic in 20%. Causative agents included ciprofloxacin, amoxicillin-clavulanate, metformin, ticlopidine, stanozolol, carbamazepine, sertraline, captopril, and droxicam. Jaundice was present in 90%, and 80% required hospitalization. Rash and eosinophilia occurred in 40%, and autoantibodies were found in two cases. Median onset time was 34 days; therapy duration averaged 32 days. Mean biochemical values: AST 4.3×ULN, ALT 8.9×ULN, ALP 2.8×ULN, GGT 10×ULN, and total bilirubin 11 mg/dL. Liver histology revealed cholestasis, portal inflammation, fibrosis, ductular reaction, and interface hepatitis. Compared to non-ductopenic DILI cases in both networks, DID patients had similar latency and clinical patterns but showed higher rates of hypersensitivity. Outcomes were favorable, with no fatalities. Liver tests normalized within 2 months to 2 years (median 3.5 months).

Conclusions

Drug-induced ductopenia is marked by pronounced hyperbilirubinemia and frequent hypersensitivity features. Unlike other series, it shows a benign course with full recovery in all reported cases.

Conflict of interest: None