Rare Clinically Significant Idiosyncratic Drug Induced Liver Injury Caused by Low Dose Atorvastatin: Time for a New Approach to Surveillance and Risk Identification

Abstract

Background: Atorvastatin is a member of the class of cholesterol lowering drugs called statins, which works by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis in the liver. Statins are used to reduce the risk of cardiovascular events in individuals who have risk factors or a history of cardiovascular disease. While atorvastatin is generally well-tolerated, like all statins, it can have some adverse effects, including Drug induced liver injury (DILI) which is rare and often dose related. However, there is scarcity of reports on symptomatic DILI occurring in patients on low dose statin and normal baseline liver function test. This case adds to the growing body of literature on the potential idiosyncratic, non-dose related adverse effects associated with atorvastatin therapy. Case report: A 69-year-old woman with history of Hypertension, Hyperlipidemia, Prediabetes, Non-Alcoholic Fatty Liver Disease (NAFLD) presented to her Primary care Physician (PCP) for regular follow up. Her Lipid panel in the last 1 year has been suboptimal with her Atherosclerotic Cardiovascular disease (ASCVD) risk score between 12.0-15.1% despite lifestyle modification. Patient was started on 10 mg of Atorvastatin daily after documenting normal baseline liver function test. Fifty-six days later, patient presented to the PCP’s office with symptoms of fatigue, nausea and, right upper abdominal pain for 3 days. She had right upper abdominal tenderness and was mildly icteric. Based on her PCPs suspicion for DILI, she was advised to discontinue atorvastatin and transferred to the emergency room for further evaluation. In the Emergency room her vitals remained stable. Liver Ultrasound showed normal sized liver with features of hepatic steatosis. Laboratory analysis showed elevated alanine aminotransferase (ALT) greater than 16 times Upper limit of normal (ULN), aspartate aminotransferase (AST) greater than 9 times ULN, while alkaline phosphatase (ALP) elevation was less than 2 times ULN suggesting hepatocellular pattern. She was seen by a hepatologist 1 week later and other etiologies of acute hepatitis were ruled out. Over the course of 4 weeks, her symptoms completely resolved and liver function tests continued to improve. Forty-six days after Atorvastatin was discontinued, her aminotransaminases returned to normal levels. Conclusion: Although DILI is usually dose dependent, this case emphasizes the need for constant monitoring of liver function test of patients on low dose statins including patients with normal baseline liver function test. Personalized medical approach involving validated predictive score for DILI may become increasingly important in tailoring statin therapy to minimize the risk of adverse effects.