Are statins (3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors) contraindicated in patients with elevated liver function tests (LFTs)?

Statins in Patients with Elevated Liver Function Tests

Statins are not contraindicated in patients with elevated liver function tests (LFTs), unless transaminase levels exceed three times the upper limit of normal or there is evidence of decompensated liver disease. 1

Assessment of Liver Function Before Starting Statins

• Baseline liver function tests are clinically prudent before initiating statin therapy to interpret potential future laboratory results or symptoms 1
• All clinical trials that studied statin efficacy excluded patients with significantly elevated liver aminotransferases, raising theoretical concerns about hepatotoxicity 1
• The risk for serious liver injury with moderate-dose statin therapy is extremely rare and did not differ from placebo in clinical trials 1

Recommendations for Patients with Elevated LFTs

• Patients with aspartate or alanine aminotransferase levels less than 3 times the upper limit of normal can safely take statins but should continue follow-up and consider repeated testing 1
• Patients with aspartate and alanine aminotransferase levels greater than 3 times the upper limit of normal should consult with their providers to evaluate the net benefit of continuing statin therapy versus adjusting or discontinuing medication 1
• Statins should be avoided in patients with evidence of worsening liver damage, decompensated cirrhosis, or acute liver failure 1, 2

Monitoring Recommendations

• Routine monitoring of liver enzymes is not recommended for all patients on statins 1
• The FDA concluded in 2012 that serious liver injury with statins is rare and unpredictable in individual patients, and routine periodic monitoring of liver enzyme levels does not appear effective in detecting or preventing this rare adverse effect 1
• Liver function tests should be checked if symptoms suggesting hepatotoxicity develop, rather than on a routine basis 3

Special Considerations for Patients with Fatty Liver Disease

• Statins are not contraindicated in patients with non-alcoholic fatty liver disease (NAFLD) and may actually improve liver enzyme elevations in these individuals 3, 4
• Patients with NAFLD are at high risk for cardiovascular morbidity and mortality, making aggressive modification of cardiovascular risk factors with statins necessary 3
• Several studies and expert opinion currently fully endorse statin use in patients with NAFLD and other chronic liver diseases if clinically indicated 4, 5

Statin Selection in Patients with Liver Disease

• When starting statins in patients with elevated LFTs, consider beginning with a lower dose and gradually titrating upward 3
• Pravastatin may have a favorable safety profile in patients who cannot tolerate other statins due to liver function abnormalities 6
• For patients with elevated LFTs, consider using moderate-dose statins rather than high-dose regimens to minimize risk 1

Common Pitfalls and Caveats

• Attributing elevated liver tests solely to statins without considering underlying fatty liver disease, which is common in patients with hyperlipidemia 4
• Withholding statins from patients who would benefit from cardiovascular risk reduction due to unfounded concerns about liver injury 5
• Failing to distinguish between clinically insignificant transaminase elevations (which are common) and true drug-induced liver injury (which is rare with statins) 7, 8
• Not recognizing that statin-induced elevations in liver enzymes are typically mild (<2x upper limit of normal) and often clinically insignificant 7

Remember that the cardiovascular benefits of statins often outweigh the minimal risk of liver injury in most patients with elevated LFTs, particularly those with NAFLD 3, 5.