Should a patient with hepatic (liver) failure be treated with a statin (HMG-CoA reductase inhibitor) if indicated?

From the Guidelines

Statins should be avoided in patients with active or decompensated hepatic failure, but can be considered in patients with stable, chronic liver disease who need lipid-lowering therapy, with careful monitoring and at the lowest possible dose, as recommended by the 2021 guidelines from the Clinical and Molecular Hepatology 1. When considering statin therapy in patients with hepatic failure, it is essential to weigh the benefits of lipid-lowering against the potential risks of hepatotoxicity and other adverse effects.

• The liver plays a crucial role in metabolizing statins, and impaired liver function can lead to drug accumulation and increased risk of toxicity, including rhabdomyolysis.
• Distinguishing between statin-induced liver injury and progression of underlying liver disease can be challenging.
• For patients with severe hepatic impairment (Child-Pugh class C), statins are contraindicated.
• Alternative lipid-lowering strategies, such as ezetimibe, which has minimal hepatic metabolism, may be safer options for these patients. The 2019 guidelines from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines also support the use of statins in patients with chronic, stable liver disease, including non-alcoholic fatty liver disease, with careful monitoring and at the lowest possible dose 1. Key considerations when prescribing statins to patients with hepatic failure include:
• Starting with the lowest possible dose (such as atorvastatin 10mg daily or rosuvastatin 5mg daily)
• Monitoring liver function tests at baseline, after 4-6 weeks of therapy, and then every 3-6 months
• Discontinuing the statin if transaminases rise to more than 3 times the upper limit of normal
• Considering alternative lipid-lowering strategies, such as ezetimibe, in patients with severe hepatic impairment.

From the FDA Drug Label

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.

Hepatic Failure and Statin Use:

• The FDA drug label states that rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis.
• It is recommended to discontinue rosuvastatin if serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs.
• Therefore, if a patient has hepatic failure, they should not be on rosuvastatin, even if they need it, due to the increased risk of hepatic injury 2.

From the Research

Statin Use in Hepatic Failure

• Patients with hepatic failure should be carefully evaluated before starting statin therapy, as the benefits and risks need to be weighed 3, 4, 5, 6, 7.
• Statins are generally well-tolerated in patients with chronic liver disease, such as nonalcoholic fatty liver disease (NAFLD), primary biliary cirrhosis, and hepatitis C virus 6, 7.
• However, decompensated cirrhosis and acute liver failure are considered contraindications for lipid-lowering therapy, as these patients are unlikely to benefit due to their grave prognosis 5, 7.
• Compensated cirrhosis is not a contraindication for statin use, but patients should be prescribed with caution and monitored frequently for adverse events 5.

Monitoring and Safety

• Routine periodic monitoring of liver function may not be necessary, but the potential for statins to cause significant and serious hepatic effects should not be overlooked 4.
• Patients with preexisting liver dysfunction, such as NAFLD, nonalcoholic steatohepatitis, compensated cirrhosis, and compensated chronic liver disease, can be treated with statins if clearly indicated, with careful monitoring of liver function 4, 5, 6, 7.
• The benefits of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweigh the risk of a very rare event of serious liver injury 7.

Specific Considerations

• Statins have pleiotropic properties that are independent of their effect on cholesterol levels, such as improving endothelial dysfunction, antioxidant, antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic, or immunomodulation properties 5.
• Statins have been studied in other areas, such as treatment of portal hypertension, prevention of hepatocellular carcinoma, and/or protection against ischemia/reperfusion injury 5.