From the Guidelines
Initiation of Angiotensin-Converting Enzyme Inhibitor (ACEI) is not absolutely contraindicated in patients with elevated liver enzymes, but caution is warranted. For patients with mild to moderate liver enzyme elevations, ACEIs like lisinopril, enalapril, or ramipril can generally be initiated at lower doses with careful monitoring, as recommended by the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1. However, in severe liver disease or acute hepatitis, ACEIs should be avoided or used with extreme caution due to potential altered drug metabolism. When starting an ACEI in a patient with elevated liver enzymes, begin with a reduced dose (e.g., lisinopril 2.5-5 mg daily instead of 10 mg), monitor liver function tests and kidney function regularly (initially after 1-2 weeks, then monthly until stable), and watch for signs of hepatic encephalopathy or worsening liver function. The concern with ACEIs in liver disease relates to their metabolism and clearance, as impaired liver function may lead to drug accumulation and increased risk of adverse effects, as noted in the 2013 ACCF/AHA guideline for the management of heart failure 1. Additionally, patients with advanced liver disease often have baseline hypotension and renal perfusion issues, making them more susceptible to ACEI-induced hypotension and renal dysfunction. If liver enzymes worsen significantly after starting an ACEI, consider discontinuation and alternative antihypertensive options like calcium channel blockers. Key considerations for the use of ACEIs in patients with elevated liver enzymes include:
- Starting with a lower dose and titrating upward as needed and tolerated
- Monitoring liver function tests and kidney function regularly
- Watching for signs of hepatic encephalopathy or worsening liver function
- Considering alternative antihypertensive options if liver enzymes worsen significantly after starting an ACEI. It is essential to weigh the potential benefits of ACEI therapy against the potential risks in patients with elevated liver enzymes, as recommended by the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1.
From the FDA Drug Label
ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical treatment.
The initiation of Angiotensin-Converting Enzyme Inhibitor (ACEI) is not directly contraindicated in patients with elevated liver enzymes. However, patients who develop marked elevations of hepatic enzymes or jaundice while on ACEI should discontinue the medication and receive appropriate medical treatment.
- Key considerations:
- Elevated liver enzymes are not a direct contraindication for ACEI initiation.
- Monitoring of liver function is essential in patients on ACEI.
- Discontinuation of ACEI is recommended if patients develop jaundice or marked elevations of hepatic enzymes. 2
From the Research
Initiation of Angiotensin-Converting Enzyme Inhibitor (ACEI) in Patients with Elevated Liver Enzymes
- There is no direct evidence to suggest that initiation of ACEI is contraindicated in patients with elevated liver enzymes 3, 4, 5, 6, 7.
- Elevated liver enzymes can be caused by various factors, including viral hepatitis, genetic liver diseases, drug-induced liver diseases, and extrahepatic diseases 3, 4.
- ACEIs are effective and well-tolerated antihypertensive agents, but their use in patients with elevated liver enzymes should be considered on a case-by-case basis 5, 6.
- Some ACEIs are metabolized via the liver, which may be advantageous in patients with renal impairment, but this does not necessarily mean that they are contraindicated in patients with elevated liver enzymes 5.
- The evaluation and management of elevated liver enzymes in patients treated with ACEIs or other medications should be based on a step-wise algorithm, taking into account the pattern of enzyme alteration, the most common causes of enzyme alteration, and initial investigations 3, 4, 7.
Considerations for ACEI Use in Patients with Elevated Liver Enzymes
- Patients with elevated liver enzymes should be evaluated for underlying liver disease or other causes of enzyme elevation before initiating ACEI therapy 3, 4.
- The use of ACEIs in patients with elevated liver enzymes should be monitored closely, with regular liver function tests and adjustments to therapy as needed 5, 6.
- The benefits and risks of ACEI therapy in patients with elevated liver enzymes should be weighed on a case-by-case basis, taking into account the individual patient's medical history, laboratory results, and clinical presentation 5, 6.