Drug-Induced Ductopenia: Natural History and p16INK4 Expression
M Westerhoff, L Hovan, G Yoshiba, R Pierce, J Hart. University of Chicago, Chicago
Background: Many medications have been documented in case reports to cause cholestasis due to bile duct damage and loss, but the histological features have not been reported for a large case series. Recently, biliary p16 expression has been noted to be a marker of cellular senescence and to be important in the pathogenesis of bile duct loss in primary biliary cirrhosis (PBC). The role of p16 expression in drug-induced ductopenia has not been reported to date.
Design: The pathology database was searched for all liver biopsies with duct loss attributable to drugs; chart reviews were then performed. Biopsies (18) were stained immunohistochemically with p16. For comparison, PBC (15) and normal liver (5) were also stained. Combined nuclear and cytoplasmic staining of bile duct epithelium was scored as positive or negative.
Results: All drug-induced ductopenia patients had elevated total bilirubin (TB) (mean 22.6 mg/dL) and alkaline phosphatase (AP) levels (mean 600 U/L) at time of biopsy. Follow-up ranged from 3 - 84 months. Table 1 displays their clinical outcomes.
|Following cessation of drug|
|Drug Class||n||Re-biopsy showed resolution of duct loss (n)||Labs and symptoms improved (n)||TB or AP remained elevated; symptoms continued (n)||Expired or transplant (n)||p16 positivity (n=6)|
|Multiple drugs, no established agent||6||1||2||3||4|