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. 1
From the Research
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 (e.g., lisinopril 2.5-5 mg daily) with careful monitoring 2. However, ACEIs should be avoided in patients with severe hepatic impairment, decompensated liver disease, or ascites due to cirrhosis. Regular monitoring of liver function tests is recommended after starting therapy, particularly during the first few weeks. The concern with ACEIs in liver disease stems from the liver's role in drug metabolism and the potential for altered drug clearance in hepatic dysfunction 2. Additionally, in advanced liver disease, the renin-angiotensin-aldosterone system is often already activated, and ACEIs could potentially worsen hemodynamics in patients with portal hypertension. If a patient has ascites or a history of hepatorenal syndrome, consultation with a hepatologist before starting an ACEI would be prudent. It's also important to note that the evaluation of liver enzyme elevations should be done using a step-wise algorithm, classifying enzyme alterations on the basis of pattern (hepatocellular, cholestatic and isolated hyperbilirubinemia) 3, 4. The most recent study on the topic of liver enzyme elevations, although focused on immunotherapy, highlights the importance of careful evaluation and monitoring of liver function in patients with elevated liver enzymes 5. In the context of antihypertensive therapy, ACEIs are effective and well-tolerated, but should be considered alternative drugs for first line therapy until randomized trials show that they are at least as effective as diuretics and beta-blockers in preventing cardiovascular morbidity and mortality 6.
Some key points to consider when initiating ACEI in patients with elevated liver enzymes include:
- Careful monitoring of liver function tests
- Lower doses of ACEIs (e.g., lisinopril 2.5-5 mg daily)
- Avoidance of ACEIs in patients with severe hepatic impairment, decompensated liver disease, or ascites due to cirrhosis
- Consultation with a hepatologist before starting an ACEI in patients with ascites or a history of hepatorenal syndrome
- Evaluation of liver enzyme elevations using a step-wise algorithm.
Overall, the decision to initiate ACEI in patients with elevated liver enzymes should be made on a case-by-case basis, taking into account the severity of liver disease, the potential benefits and risks of ACEI therapy, and the need for careful monitoring and follow-up.