Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion A case report

Rationale: The purpose of this study was to identify the chemical responsible for cholestatic hepatitis in a 55-year-old woman who ingested 1,10-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. Postmortem 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 mu M 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.