From the Guidelines
High cholesterol can indirectly cause elevated Liver Function Tests (LFTs) through conditions like non-alcoholic fatty liver disease (NAFLD), but direct evidence linking high cholesterol to elevated LFTs is limited. The relationship between high cholesterol and liver function is complex, with liver disease also affecting cholesterol metabolism 1. According to the 2014 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline, measuring baseline liver function tests is clinically prudent to interpret potential future laboratory results or symptoms, especially when initiating statin therapy 1.
Key points to consider:
- High cholesterol can contribute to the development of NAFLD, which may lead to elevated LFTs
- Statins, used to treat high cholesterol, can cause liver enzyme elevations as a side effect, although this is typically rare and unpredictable in individual patients 1
- Regular monitoring of both cholesterol levels and liver function is important to track improvement and detect any medication side effects early
- Lifestyle changes, such as weight loss, reduced saturated fat intake, increased physical activity, and limiting alcohol consumption, can improve both high cholesterol and elevated LFTs simultaneously
The VA/DoD suggests assessing for evidence of liver damage before initiating statin therapy and avoiding statins in patients with evidence of worsening liver damage or fluctuating results on liver function tests 1. However, routine periodic monitoring of liver enzyme levels does not seem to be effective in detecting or preventing rare adverse effects like serious liver injury 1. Therefore, the focus should be on managing high cholesterol and monitoring liver function as part of a comprehensive approach to reducing cardiovascular risk and improving overall health.
From the FDA Drug Label
Liver Enzyme Abnormalities and Monitoring: Increases in serum transaminases have been reported with use of ezetimibe tablets. Increases in serum transaminases have been reported with use of ezetimibe tablets [see Adverse Reactions (6.1)].
The FDA drug label does not directly answer whether hypercholesterolemia can cause elevated Liver Function Tests (LFTs). The label discusses the potential for ezetimibe to cause increases in liver enzymes, but it does not address the relationship between hypercholesterolemia and LFTs 2, 2.
From the Research
Hypercholesterolemia and Elevated Liver Function Tests (LFTs)
- Hypercholesterolemia, or high cholesterol, is a condition that can increase the risk of cardiovascular disease 3.
- Elevated Liver Function Tests (LFTs) can be caused by various factors, including statin use, which is a common treatment for hypercholesterolemia 4, 5, 6, 7.
- Studies have shown that statins can cause elevations in aminotransferases in up to 3% of treated patients, but these elevations are usually mild and resolve spontaneously 4, 7.
- In some cases, statins may even have a beneficial therapeutic effect on the underlying liver disease, such as nonalcoholic fatty liver disease (NAFLD) 4, 6.
Statin Use and LFTs
- The pattern of liver injury with statin use is not specific, and a correlation over time may not be apparent 5.
- A study of 204 patients taking statins found that elevations of LFTs were seen with both rosuvastatin and atorvastatin, but these elevations were almost always <2x the upper limit of normal (ULN) 5.
- Another study found that statins may increase response rates of antiviral therapy for hepatitis C, and may have a beneficial effect on LFTs in patients with NAFLD 4.
- The risk of hepatic injury caused by statins is estimated to be about 1 percent, similar to that of patients taking a placebo 7.
Safety of Statin Use in Patients with Elevated LFTs
- Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins, and often the elevations will resolve spontaneously 7.
- Coexisting elevations of transaminase levels from nonalcoholic fatty liver disease and stable hepatitis B and C viral infections are not contraindications to statin use 7.
- Clinically important drugs that interact with statins and increase the risk of adverse effects include fibrates, diltiazem, verapamil, and amiodarone 7.