Hepatotoxicity Associated with a Short Course of Rosuvastatin

Statins reduce cardiovascular morbidity and mortality with dyslipidemia. Although generally well‑tolerated, dose‑dependent adverse events develop in 10%–15% patients. In addition, up to 3% patients have mildly elevated serum aminotransferase levels within the 1 st year of therapy that are rarely associated with symptoms. We report a case of clinically significant hepatotoxicity after a very brief course of rosuvastatin in a statin‑naive patient. A 76‑year‑old man presented with new‑onset right upper quadrant pain. There was no fever, chills, jaundice, hepatosplenomegaly, or indications of chronic liver disease on physical examination. His past medical history included subtotal gastrectomy for advanced gastric cancer 14 years prior to this presentation, hypertension for 10 years, and ischemic heart disease since 2 years. There was no history of liver diseases. Twelve days before this presentation, he was diagnosed with unstable angina pectoris, treated with percutaneous coronary intervention, and administered anti‑ischemic medications (clopidogrel, 75 mg/d; rosuvastatin, 10 mg/d) as well as maintenance medications (aspirin, carvedilol, diltiazem, isosorbide mononitrate, barnidipine, and eprosartan) for stable ischemic heart disease, taken since 20 months. Although baseline liver enzyme levels were within normal limits, marked elevation was subsequently observed (serum bilirubin 10.3 mg/L; alkaline phosphatase 174 IU/L; aspartate aminotransferase 1558 IU/L; alanine aminotransferase 613 IU/L). Other pertinent laboratory examinations performed in consideration of the differential diagnoses for abnormal liver biochemistries were negative, including anti‑hepatitis A virus antibody IgM, hepatitis B surface antigen, anti‑hepatitis C virus antibody, anti‑nuclear antibody, anti‑smooth muscle antibody, anti‑mitochondrial antibody, and anti‑liver‑kidney microsomal antibody. Computed tomography with contrast showed a normal liver. A liver biopsy was not performed. A re‑challenge test with rosuvastatin was not conducted for ethical reasons. Rosuvastatin and the other potentially hepatotoxic medications were discontinued, except for the dual antiplatelet agents. Liver function returned to normal within 4 days. All the medications except rosuvastatin were subsequently resumed without further liver enzyme abnormalities. The patient's biochemical course is summarized in Figure 1. Based on a Roussel Uclaf Causality Assessment Method overall score of 9 point, our patient had drug‑induced hepatotoxicity. This method provides a standardized scoring system in which the limits and contents of most criteria were decided by consensus among experts on the basis of organ‑oriented characteristics and had its complexity as a major disadvantage. After ruling out other differential diagnoses for the severe hepatitis, we concluded that rosuvastatin‑induced hepatotoxicity. Given that rosuvastatin‑induced hepatitis usually occurs 3 months after administration, [1] it is extremely rare for severe …