From the Guidelines
Atorvastatin and simvastatin have the highest risk of liver enzyme elevations among statins, as evidenced by the PROVE-IT study which showed a greater incidence of liver enzyme elevation with 80 mg/day of atorvastatin compared to 40 mg/day of pravastatin 1.
Statin-Associated Liver Effects
The liver effects of statins are a concern, particularly with certain statins that are metabolized primarily through the liver's cytochrome P450 system.
- Atorvastatin and simvastatin are associated with a higher risk of liver enzyme elevations due to their metabolism via the CYP3A4 pathway.
- Rosuvastatin and pravastatin, on the other hand, have lower risks of liver effects because they undergo less hepatic metabolism.
Monitoring and Management
When starting any statin, liver function tests should be monitored, especially during the first few months of therapy, as recommended by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1.
- Patients with pre-existing liver disease require more careful monitoring and possibly lower starting doses.
- The liver effects typically manifest as asymptomatic elevations in transaminases (ALT and AST), which are often transient and resolve even with continued therapy.
- Severe liver injury from statins is rare, occurring in approximately 1 in 100,000 patients.
- If a patient develops liver enzyme elevations greater than three times the upper limit of normal, the statin should be temporarily discontinued and liver function reassessed, as suggested by the guideline 1.
From the FDA Drug Label
8.7 Hepatic Impairment Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury
The statin that affects the liver is rosuvastatin.
- Contraindications include acute liver failure or decompensated cirrhosis.
- Increased risk of hepatic injury in patients with chronic alcohol liver disease or history of liver disease 2
From the Research
Statin Effects on Liver Enzymes
- The use of statins in patients with elevated plasma aminotransferases may result in normalization of these liver enzymes 3.
- Atorvastatin was associated with a higher risk of 1-year all-cause mortality than rosuvastatin in patients with elevated liver enzymes following acute myocardial infarction 4.
- Simvastatin did not show statistically significant improvement in aminotransferase levels compared to placebo in patients with biopsy-proven non-alcoholic steatohepatitis (NASH) 3.
- Atorvastatin may be associated with severe, asymptomatic liver injury in a hepatocellular pattern, which improved rapidly with cessation of the drug 5.
Statin Comparison
- Rosuvastatin use was related to significant histological ameliorating effects in the setting of NASH, and may offer substantial liver- and cardiovascular disease-related adverse event reduction 6.
- Atorvastatin and rosuvastatin are considered safe for use in patients with non-alcoholic fatty liver disease (NAFLD) and NASH, with potential benefits in reducing cardiovascular disease events and hepatocellular carcinoma risk 6.
- The risk of clinically significant idiosyncratic drug-induced liver injury from statins is quite small, with preclinical data suggesting potential hepatoprotective effects of statin therapy 7.
Liver Injury and Statins
- Statins may occasionally be associated with mild transaminase elevations, but can also result in life-threatening liver injury 5, 7.
- Atorvastatin is the most common cause of clinically significant liver injury in the statin drug class 5.
- Liver histology was not significantly affected by simvastatin in patients with NASH, and no data on histological changes were reported for atorvastatin 3.