What is the impact of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, on liver function?

From the Guidelines

Statins can be safely used in patients with liver disease, including non-alcoholic fatty liver disease (NAFLD), as they have been shown to improve liver biochemistries and reduce cardiovascular risk without increasing the risk of serious liver injury. The use of statins in patients with liver disease has been a topic of debate, but recent studies have provided evidence to support their safety and efficacy in this population. According to a study published in 2021 1, statin use decreased aminotransferases and poor cardiovascular outcomes in NAFLD patients with aminotransferases up to three times higher than the upper normal limit. Another study published in 2012 1 found that statins are safe in patients with liver disease and that there is no evidence that patients with chronic liver disease, including NAFLD and NASH, are at higher risk for serious liver injury from statins than those without liver disease.

Some key points to consider when using statins in patients with liver disease include:

• Monitoring liver function before starting statins and periodically during treatment, especially with higher doses
• Patients with pre-existing liver disease may still use statins but require closer monitoring
• If liver enzymes rise to more than three times the upper limit of normal, doctors may consider reducing the dose or switching to a different statin
• Patients should report symptoms like unusual fatigue, loss of appetite, right upper abdominal discomfort, dark urine, or yellowing of the skin or eyes, as these could indicate liver problems requiring immediate medical attention

It's also important to note that statins can cause mild elevations in liver enzymes, but serious liver damage is rare, occurring in fewer than 1 in 100,000 patients 1. Overall, the benefits of statin use in patients with liver disease, including improved liver biochemistries and reduced cardiovascular risk, outweigh the risks, and they can be a valuable treatment option for these patients.

From the FDA Drug Label

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 impact of HMG-CoA reductase inhibitors, such as rosuvastatin, on liver function is that they may increase the risk of hepatic injury in patients with a history of liver disease or those who consume substantial quantities of alcohol.

• Contraindications include acute liver failure or decompensated cirrhosis.
• Increased risk of hepatic injury is associated with chronic alcohol liver disease and substantial alcohol consumption. 2

From the Research

Impact of Statins on Liver Function

• Statins can cause transient elevation of liver enzymes in some patients, but this does not necessarily lead to serious liver injury 3, 4.
• The risk of serious liver injury associated with statin use is very low, and routine periodic monitoring of liver function may not be necessary 5.
• Statins may have a beneficial therapeutic effect in treating underlying liver disease, such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) 4, 6.
• Studies have shown that statins can improve liver histological and functional alterations in patients with NAFLD or NASH, and may reduce the risk of cardiovascular events in these patients 6.

Liver Injury Associated with Statin Use

• High-dose atorvastatin therapy has been associated with severe liver injury, but this is a rare occurrence 7.
• Atorvastatin is the most common cause of clinically significant liver injury among statins, but the risk of liver injury can be mitigated by monitoring liver function and adjusting the dose or switching to a different statin if necessary 7, 5.

Use of Statins in Patients with Preexisting Liver Dysfunction

• Statins can be safely used in patients with preexisting liver dysfunction, such as NAFLD, NASH, compensated cirrhosis, and compensated chronic liver disease, if the benefits of statin use outweigh the risks 4, 6, 5.
• Physician judgment is important when deciding whether to use statins in patients with preexisting liver dysfunction, and the decision should be based on the individual patient's risk and benefit profile 5.