What are the implications of elevated Liver Function Tests (LFTs) in a patient taking Atorvastatin (Lipitor)?

From the Guidelines

Atorvastatin should be temporarily discontinued if liver function tests (LFTs) are significantly elevated, typically when alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceed 3 times the upper limit of normal (ULN), as suggested by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1. For mild elevations (less than 3x ULN), close monitoring every 4-6 weeks may be appropriate while continuing the medication, as the risk of liver injury is generally low and the cardiovascular benefits of statins often outweigh this risk 1. After LFTs normalize, atorvastatin can often be reintroduced at a lower dose (such as 10 mg daily) with gradual titration as tolerated, along with more frequent LFT monitoring (initially every 2-4 weeks) 1. Some key points to consider when managing atorvastatin with elevated LFTs include:

• Investigating other potential causes of elevated LFTs, including alcohol use, hepatitis, and other medications 1
• Considering alternative statins like rosuvastatin or pravastatin if LFT elevations recur, as they undergo less hepatic metabolism 1
• Educating patients about symptoms of liver injury such as fatigue, abdominal pain, jaundice, or dark urine, which warrant immediate medical attention 1
• Weighing the cardiovascular benefits of statins against the risk of liver injury, and making decisions on a case-by-case basis 1. It's also important to note that statin-induced liver injury is typically reversible upon discontinuation, and that the administration of statins is possible in chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), but should be avoided in patients with decompensated cirrhosis or acute liver failure 1.

From the FDA Drug Label

Increases in serum transaminases have been reported with use of atorvastatin calcium tablets [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. Persistent increases to more than three times the ULN in serum transaminases have occurred in approximately 0. 7% of patients receiving atorvastatin calcium tablets in clinical trials. Consider liver enzyme testing before atorvastatin calcium tablets initiation and when clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue atorvastatin calcium tablets.

Atorvastatin with elevated LFTs:

• The drug label recommends considering liver enzyme testing before initiating atorvastatin calcium tablets and when clinically indicated thereafter.
• If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, atorvastatin calcium tablets should be promptly discontinued.
• Persistent increases to more than three times the ULN in serum transaminases have occurred in approximately 0.7% of patients receiving atorvastatin calcium tablets in clinical trials 2.

From the Research

Atorvastatin and Elevated LFTs

• Atorvastatin, a commonly prescribed statin, can cause elevations in liver function tests (LFTs) in some patients 3, 4, 5, 6, 7.
• Studies have shown that these elevations are usually mild and do not lead to significant liver toxicity over time 3, 5, 7.
• The pattern of liver injury with statin use, including atorvastatin, is not specific and a correlation over time may not be apparent 3.
• Elevations of LFTs with atorvastatin are almost always <2x the upper limit of normal (ULN), with greater elevations seen at higher doses (e.g., 40 mg/day) 3.
• The derangement in LFTs persists and improvement is not seen, but these elevations are clinically and statistically insignificant and should not deter physicians from prescribing or continuing statins 3.

Clinical Guidance

• Physicians should order liver function tests before starting statin therapy, 12 weeks after initiation, with any dose increase, and periodically for long-term maintenance therapy 5.
• Mild elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (<3 times the upper limit of normal [ULN]) following statin therapy do not appear to lead to significant liver toxicity over time 5.
• Statins, including atorvastatin, may be well tolerated and even beneficial in patients with elevated liver tests, especially those with nonalcoholic fatty liver disease (NAFLD) 6.