Ezetimibe metabolite as a non-invasive biomarker for non-alcoholic steatohepatitis (nash)

A method for diagnosing a hepatic disorder in a human subject, die method comprising:

• a) administering ezetimibe (EZE) to the human subject;
• b) obtaining a sample from the human subject after a period of time from when the human subject was administered EZE;
• c) determining an amount of EZE, ezetimibe-glucuronide (EZE-Gluc), or both in the sample obtained from the human subject;
• d) comparing the amount of EZE, EZE-Gluc, or both to a control;
• and
• e) diagnosing the human subject with the hepatic disorder when the amount of EZE, EZE-Gluc, or both in the sample is elevated relative to the control.

A method of treating a hepatic disorder in a human subject in need of such treatment, the method comprising:

• a. administering ezetimibe (EZE) to the subject;
• b. obtaining, a non-biopsy, fluid sample after a period of time has passed from administering the EZE;
• c. measuring an amount of EZE, ezetimibe-glucuronide (EZE-Gluc), or both in the fluid sample;
• d. comparing the amount of EZE-EZE-Gluc, or both to a reference value, wherein a deviation of the amount of EZE, EZE-Gluc, or both from the reference value indicates a stage of the hepatic disease;
• and
• e. prescribing a therapy to the subject based on the stage of the hepatic disorder.

A method for delineating non-alcoholic steatohepatitis (NASH) from simple steatosis in a human subject, the method comprising

• a) administering ezetimibe (EZE) to the human subject;
• b) determining an amount of ELF, ezetimibe-glucuronide (EZE-Gluc), or both in non-biopsy sample obtained from the human subject after a period of time from when the human subject was administered EZE;
• c) comparing the amount of ELF, EYE-Glue, or both to a control, wherein the control is obtained from a human subject with steatosis;
• and
• d) determining that the human subject has NASH when the amount of EZE, EZE-Gluc, or both is elevated relative to the control.