In addition, the FDA was cautious of the concerning benefit-to-risk profile of OCA due to its plentiful adverse effects, many of which were due to overtly strong systemic FXR agonism and repression of BA synthesis: drug-induced liver injury, excess risk of cholecystitis and bile stones, risk of new-onset dyslipidemia needing statin treatment, excessive risk for new-onset prediabetes/diabetes, acute kidney injury, and severe pruritis requiring discontinuation.7 The gene discussed is NR1H4; the disease is metabolic syndrome.