What is the relationship between Rosuvastatin (Crestor) and elevated liver enzymes, specifically hepatocellular injury or abnormal liver function tests?

From the Guidelines

Crestor (rosuvastatin) can be safely continued in patients with elevated liver enzymes, as the risk of serious liver injury is rare, and the benefits of statin therapy in reducing cardiovascular risk often outweigh the risks, as supported by the 2012 guidelines from the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association 1. When considering the management of elevated liver enzymes in patients taking Crestor, it's essential to weigh the benefits of statin therapy against the potential risks. The evidence suggests that statins, including Crestor, are generally safe in patients with liver disease, and the risk of serious liver injury is low 1.

• Key points to consider:
  • Elevated liver enzymes are a common side effect of statin therapy, but serious liver damage is rare 1.
  • The mechanism behind statin-induced liver enzyme elevation involves the drug's effect on liver metabolism 1.
  • Liver function tests are typically performed before starting statin therapy and periodically thereafter, especially during the first year 1.
  • Significant elevations (greater than three times the upper limit of normal) occur in approximately 1% of patients taking Crestor, and alternative cholesterol-lowering medications may be considered if liver concerns persist 1. In clinical practice, the decision to continue or modify statin therapy in patients with elevated liver enzymes should be made on a case-by-case basis, taking into account the individual patient's risk factors, medical history, and the potential benefits of statin therapy in reducing cardiovascular risk, as recommended by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1.

From the FDA Drug Label

Increases in serum transaminases have been reported with use of rosuvastatin [see Adverse Reactions (6. 1)] . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to more than three times the ULN occurred in 1.1% of patients taking rosuvastatin versus 0. 5% of patients treated with placebo.

Marked persistent increases of hepatic transaminases have also occurred with rosuvastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8. 7)] .

Consider liver enzyme testing before rosuvastatin initiation and when clinically indicated thereafter. Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)] .

If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue rosuvastatin.

Crestor and Elevated Liver Enzymes:

• Elevated liver enzymes have been reported in patients taking rosuvastatin.
• The risk of hepatic injury is increased in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
• Liver enzyme testing is recommended before initiating rosuvastatin and when clinically indicated thereafter.
• Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis.
• If serious hepatic injury occurs, rosuvastatin should be promptly discontinued 2.

From the Research

Crestor and Elevated Liver Enzymes

• Crestor, also known as rosuvastatin, is a statin medication used to lower cholesterol levels in the blood 3, 4, 5.
• Elevated liver enzymes can be a side effect of statin medications, including Crestor 3, 4, 5.
• However, elevated liver enzymes can also be caused by other factors, such as muscle damage or exercise-induced changes in hepatocyte membrane permeability 6, 7.
• In some cases, elevated liver enzymes may not necessarily imply an underlying liver pathology 6.
• Studies have shown that rosuvastatin can cause liver toxicity, but the risk is considered low 3, 4, 5.
• A study of over 100,000 statin users in UK primary care found no evidence that patients prescribed rosuvastatin were at greater risk of liver injury or other adverse outcomes compared to patients prescribed other statins 5.

Possible Causes of Elevated Liver Enzymes

• Muscle damage or injury, which can elevate transaminase levels 6, 7.
• Exercise-induced changes in hepatocyte membrane permeability 7.
• Drug-induced liver injury (DILI), which can be caused by statin medications, including Crestor 3, 4.
• Other underlying medical conditions, such as hepatitis or liver disease 3, 7.

Diagnostic Considerations

• Liver function tests (LFTs) should be interpreted in the context of the patient's medical history, physical examination, and other laboratory results 6, 7.
• Muscle biomarkers, such as creatine kinase, should be considered in the diagnostic workup of patients with elevated LFTs, especially if they have a history of muscle injury or exercise-induced changes in hepatocyte membrane permeability 7.
• A liver biopsy may be necessary to confirm the diagnosis of liver injury or disease 3, 7.