From the Guidelines
Statins should not be initiated in patients with significantly elevated liver function tests (LFTs), typically defined as transaminases (ALT/AST) exceeding three times the upper limit of normal, due to the risk of worsening liver damage. According to the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1, if ALT is less than 3 times the upper limit of normal (ULN), statin therapy can be continued with rechecking of liver enzymes in 4-6 weeks. However, if the value rises to ≥3x ULN, the guidelines suggest re-evaluating the indication for statin treatment.
In patients with nonalcoholic fatty liver disease (NAFLD), statins can be considered for dyslipidemia management, as they have been shown to decrease aminotransferases and poor cardiovascular outcomes in NAFLD patients with aminotransferases up to three times higher than the upper normal limit 1. The 2021 KASL clinical practice guidelines for the management of NAFLD suggest that statins can be used in NAFLD and NASH, and are considered a first-line treatment to lower LDL-C and prevent atherosclerotic CVD.
Some key points to consider when using statins in patients with elevated LFTs include:
- Monitoring liver enzymes (ALT) at baseline, 8-12 weeks after starting therapy, and periodically thereafter 1
- Avoiding statin use in patients with decompensated cirrhosis or acute liver failure 1
- Considering alternative lipid-lowering strategies like ezetimibe, PCSK9 inhibitors, or bile acid sequestrants if statins are contraindicated
- Cautiously reintroducing statins under close supervision once LFTs normalize or improve significantly.
Overall, the decision to use statins in patients with elevated LFTs should be made on a case-by-case basis, taking into account the potential benefits and risks of statin therapy, as well as the presence of any underlying liver disease.
From the FDA Drug Label
Increases in serum transaminases have been reported with use of ezetimibe tablets [see Adverse Reactions (6.1)]. In controlled clinical combination studies of ezetimibe tablets initiated concurrently with a statin, the incidence of consecutive elevations (≥3 X ULN) in hepatic transaminase levels was 1.3% for patients treated with ezetimibe tablets administered with statins and 0. 4% for patients treated with statins alone. Perform liver enzyme testing as clinically indicated and consider withdrawal of ezetimibe tablets if increases in ALT or AST ≥3 X ULN persist.
The FDA drug label does not directly answer why statins can't be used with elevated LFTs, but it does mention that liver enzyme abnormalities have been reported with the use of ezetimibe tablets, especially when used in combination with a statin. It is recommended to perform liver enzyme testing as clinically indicated and consider withdrawal of the medication if increases in ALT or AST ≥3 X ULN persist 2. However, the label does not provide a direct contraindication for using statins with elevated LFTs.
From the Research
Statins and Elevated Liver Function Tests (LFTs)
- Statins can cause dose-dependent borderline elevations of liver function tests over time, but these elevations are typically clinically and statistically insignificant 3.
- Elevations of LFTs are seen with both rosuvastatin and atorvastatin, with greater elevations seen with atorvastatin 40 mg/day 3.
- Statins are associated with elevations in aminotransferases in up to 3% of treated patients, but rarely lead to serious drug-induced liver injury (DILI), chronic liver disease, or acute liver failure 4.
Safety of Statin Use with Elevated LFTs
- Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins, as the elevations will often resolve spontaneously 5.
- Coexisting elevations of transaminase levels from nonalcoholic fatty liver disease and stable hepatitis B and C viral infections are not contraindications to statin use 5.
- Statins may have a beneficial therapeutic effect in treating the underlying liver disease, particularly in patients with nonalcoholic fatty liver disease (NAFLD) 4.
Alternative Treatment Options
- Ezetimibe can be an effective and safe alternative for treating hypercholesterolemia in patients with elevated LFTs, particularly in liver transplant recipients 6.
- Ezetimibe acts through inhibition of enterohepatic recirculation of lipids, unlike statins, which may be beneficial in patients with chronic liver disease 6.
Evaluation of Abnormal LFTs
- Evaluation of abnormal LFTs in hospitalized patients should be organized into four steps: determining the association with the current illness, determining the etiology of the underlying liver disease, evaluating the severity of liver dysfunction, and looking for associated complications 7.