Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion

RATIONALE The purpose of this study was to identify the chemical responsible for cholestatic hepatitis in a 55-year-old woman who ingested 1,1'-iminodi (octamethylene) diguanidinium triacetate (iminoctadine triacetate), a fungicide. The fungicide formulation was also composed of polyoxyethylene nonylphenol (NP-40) and methanol. PATIENT CONCERNS Severe cholestatic hepatitis developed, which led to the patient's death on day 88 of hospitalization. Post-mortem necropsy of the liver showed focal hepatocyte necrosis involving mostly the mid-zone, along with intracytoplasmic and intracanalicular cholestasis. DIAGNOSES To identify the chemical responsible for hepatic injury, the cellular toxicity of all chemicals in the fungicide formulation was assessed in HepG2 cells using the 3-(4,5-dimethylthiaxol-2yl)-2, 5-diphenyl tetrazolium bromide test. OUTCOMES Viability of cells treated with the surfactant NP-40 was significantly lower (P < .001), but that of cells treated with other components of the fungicide, including the active ingredient, iminoctadine triacetate, was unaffected. Fluorescence-activated cell sorting analysis confirmed that necrosis was induced in HepG2 cells treated with 25-80 μM of NP-40, while significant numbers of apoptotic cells were not detected. LESSONS NP-40 appears to be the chemical responsible for the patient's irreversible hepatic injury, accompanied by intracytoplasmic and intracanalicular cholestasis.