Can Suboxone (buprenorphine) cause elevated liver function tests (LFTs)?

Suboxone and Elevated Liver Function Tests

Yes, Suboxone (buprenorphine) can cause elevated liver function tests (LFTs), particularly in patients with pre-existing liver conditions such as hepatitis C. Monitoring of liver enzymes is recommended for patients on buprenorphine therapy, especially those with risk factors for liver disease.

Risk Factors for Buprenorphine-Associated Liver Enzyme Elevations

• Patients with hepatitis C infection have significantly higher risk of developing liver enzyme elevations when treated with buprenorphine 1, 2
• HIV/HCV co-infected patients show approximately 7-fold increased risk of liver enzyme elevations compared to uninfected patients 2
• Higher doses of buprenorphine are associated with greater odds of AST elevation (odds ratio = 1.23 per 1 mg increase in dose) 1
• Pre-existing liver disease increases susceptibility to buprenorphine-induced liver injury 3

Mechanism of Liver Injury

• Buprenorphine may affect hepatocyte metabolism in a dose-dependent manner 4
• At therapeutic concentrations (10 μM), buprenorphine can reduce albumin synthesis by approximately 50% in human hepatocytes 4
• Buprenorphine is metabolized through cytochrome P450 3A4, which may contribute to idiosyncratic hepatotoxicity in susceptible individuals 3
• Direct mitochondrial toxicity has been proposed as a potential mechanism for liver injury 3

Clinical Presentation and Severity

• Most cases of buprenorphine-associated LFT elevations are mild and asymptomatic 2
• Severe cases of acute liver failure have been reported, though rare, particularly in patients with underlying hepatitis C 3
• Liver enzyme elevations typically occur within the first few weeks to months of treatment 1
• Both hepatocellular (elevated ALT/AST) and cholestatic patterns (elevated alkaline phosphatase) of injury can occur 2

Monitoring Recommendations

• Baseline liver function tests should be obtained before initiating buprenorphine therapy 5
• For patients with normal baseline LFTs and no risk factors, monitoring can be performed periodically (every 3-6 months) 5
• For patients with pre-existing liver disease (especially hepatitis C):
  • More frequent monitoring is recommended, particularly during the first 1-2 months of treatment 1, 2
  • Consider monthly monitoring for the first 3-6 months, then quarterly if stable 5
• Discontinuation or dose reduction should be considered if ALT or AST rise to >3 times the upper limit of normal 5

Management of Elevated LFTs

• For mild elevations (<3x upper limit of normal) without symptoms:
  • Continue buprenorphine with close monitoring 5
  • Consider more frequent LFT monitoring (every 2-4 weeks) 5
• For moderate elevations (3-5x upper limit of normal):
  • Consider dose reduction 1
  • Increase frequency of monitoring 5
• For severe elevations (>5x upper limit of normal) or any elevation with symptoms:
  • Temporarily discontinue buprenorphine 3
  • Evaluate for other causes of liver injury 5
  • Consider hepatology consultation 5

Clinical Considerations

• The benefits of buprenorphine treatment for opioid use disorder often outweigh the risks of mild LFT elevations 2
• Abrupt discontinuation of buprenorphine can lead to withdrawal and increased risk of relapse to illicit opioid use 2
• Patients with elevated LFTs on buprenorphine should be evaluated for other causes of liver injury, including alcohol use, viral hepatitis, and other hepatotoxic medications 5
• In patients who develop significant hepatotoxicity, alternative treatments for opioid use disorder should be considered 3