Starting Repatha in Patients with Elevated Liver Function Tests
Repatha (evolocumab) can be safely initiated in patients with elevated liver function tests as it has no contraindications related to liver function abnormalities and does not require dose adjustment for hepatic impairment. 1
Safety Profile of Repatha and Liver Function
Repatha is a PCSK9 inhibitor monoclonal antibody that works by binding to PCSK9 and increasing the number of LDL receptors available to clear circulating LDL-C. According to the 2022 American College of Cardiology expert consensus:
- The only contraindication for Repatha is a history of hypersensitivity to the medication 1
- There are no warnings or precautions related to liver function in the FDA labeling 1
- The primary adverse effects reported in clinical trials include nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions 1
Unlike many other lipid-lowering medications such as statins, Repatha has not been associated with hepatotoxicity in clinical trials.
Clinical Evidence Supporting Safety
The FOURIER trial, which evaluated evolocumab in 27,564 patients with atherosclerotic cardiovascular disease, demonstrated that:
- Evolocumab significantly reduced LDL-C levels by approximately 59% compared to placebo 2
- There was no significant difference between study groups with regard to adverse events, with the exception of injection site reactions 2
- No safety signals related to liver function were identified in this large outcomes trial 2
Long-term safety data from studies of patients with familial hypercholesterolemia showed that evolocumab was well-tolerated over a median of 4.1 years of treatment, with no specific liver-related concerns reported 3.
Monitoring Recommendations
While Repatha itself does not require specific liver function monitoring, it's prudent to:
- Establish baseline liver function tests before initiating therapy
- Monitor liver function periodically as part of routine care, especially if the patient is on other medications that may affect liver function
- Follow standard monitoring practices for patients with pre-existing liver disease
Management Algorithm for Patients with Elevated LFTs
Assess the degree of LFT elevation:
- Mild elevation (<3× ULN): Proceed with Repatha without dose adjustment
- Moderate elevation (3-5× ULN): Investigate underlying cause but can start Repatha
- Severe elevation (>5× ULN): Consider addressing underlying liver disease first, but Repatha itself is not contraindicated
Evaluate for other causes of elevated LFTs:
- Alcohol use (AST/ALT ratio >2 suggests alcoholic liver disease) 4
- Medications (particularly statins or other hepatotoxic drugs)
- Non-alcoholic fatty liver disease (NAFLD)
- Viral hepatitis
- Autoimmune hepatitis
Consider concurrent medications:
- If patient is on statins with elevated LFTs, the American College of Cardiology recommends not discontinuing statins for mild, asymptomatic elevations in transaminases 4
- Repatha can be safely added to statin therapy regardless of mild LFT elevations
Special Considerations
- For patients with NASH and elevated baseline ALT, using multiples of baseline rather than multiples of ULN may be more appropriate for monitoring liver function 1
- If LFTs worsen significantly after starting Repatha, investigate other causes, as the medication itself is not known to cause liver injury
When to Refer to Hepatology
Consider referral to hepatology if:
- ALT/AST increases to >5× ULN
- ALT/AST >3× ULN with total bilirubin ≥2× ULN
- Persistent elevation >6 months despite interventions
- Development of symptoms such as jaundice, abdominal pain, or fatigue 4
In conclusion, Repatha is a safe option for patients with elevated liver function tests who require additional LDL-C lowering therapy. Unlike many other lipid-lowering agents, it does not have specific contraindications or warnings related to liver function and can be initiated without dose adjustment for hepatic impairment.