What medications can affect liver function test results, particularly those that are metabolized by the liver?

Medications That Affect Liver Function Tests

Numerous medications can alter liver function test results through direct hepatotoxicity, metabolic effects, or idiosyncratic reactions, with antibiotics, statins, NSAIDs, antituberculous drugs, and immunosuppressants being the most common culprits requiring baseline and ongoing monitoring.

Major Drug Classes Affecting LFTs

Antibiotics

Antibiotics are the most frequently reported drug class causing drug-induced liver injury (DILI) across all major studies 1, 2. Key considerations include:

• Amoxicillin-clavulanate: Causes delayed-onset liver injury, sometimes occurring weeks after exposure 1
• Cefazolin: Can lead to liver injury 1-3 weeks after a single infusion 1
• Nitrofurantoin: May cause liver injury after years of treatment, potentially leading to acute liver failure or autoimmune-like reactions 1
• Isoniazid: Causes hepatitis in a significant proportion of patients, requiring baseline and monthly monitoring of liver enzymes for the first 3 months 3
• Ethionamide: Produces hepatotoxicity in approximately 2% of patients 3
• Macrolides (clarithromycin, azithromycin): Require periodic monitoring of alkaline phosphatase, AST, and ALT for the first 3 months 3

Statins

Statins cause dose-dependent elevations in liver transaminases 4, 5:

• Atorvastatin: Persistent increases to more than 3x the upper limit of normal (ULN) occur in approximately 0.7% of patients 4
• Rosuvastatin and atorvastatin: Cause borderline LFT elevations that are typically <2x ULN, with greater elevations seen with atorvastatin 40 mg/day 5
• Liver enzyme testing should be performed before initiation and when clinically indicated thereafter 4
• Patients consuming substantial alcohol or with pre-existing liver disease are at increased risk 4

NSAIDs

NSAIDs can cause hepatotoxicity, though serious hepatic disease is rare 3, 2, 6:

• Should be avoided in patients with GFR <30 mL/min/1.73 m² 3
• Monitoring of liver function is generally infrequent in clinical practice, though more common with diclofenac 6
• Are among the most commonly implicated agents in DILI 2

Retinoids

Acitretin causes elevation in transaminases in 13-16% of patients 3:

• Baseline liver function tests are mandatory 3
• Monthly monitoring is required if underlying liver disease exists 3
• Major increases in LFTs suggest toxic hepatitis and require prompt discontinuation 3

Antituberculous Medications

Multiple TB drugs affect liver function 3:

• Rifampin/Rifabutin: Cause hepatitis; require AST/ALT monitoring based on symptoms 3
• Isoniazid: Requires periodic ALT/AST determinations, especially in first 3 months 3
• Ethionamide: Structurally similar to INH; causes hepatotoxicity in ~2% of patients 3

Immunosuppressants and Antivirals

Several agents require careful hepatic monitoring 3:

• Colchicine: Children may experience elevated LFTs during viral infections, especially when combined with NSAIDs or antibiotics 3
• Methotrexate: Requires dose reduction when GFR <60 mL/min/1.73 m² 3
• Direct-acting antivirals (DAAs): Hepatic panels should be monitored at 2-4 week intervals until resolution when treating acute hepatitis C 3

Monitoring Recommendations

Baseline Testing

Before initiating potentially hepatotoxic medications 3, 7, 4:

• Liver function tests (AST, ALT, alkaline phosphatase, bilirubin) should be checked to rule out pre-existing dysfunction
• Consider HLA-B*15:02 screening before carbamazepine in Asian patients 7

Ongoing Monitoring Schedule

The frequency depends on the specific medication 3, 7:

• First 3 months: Monthly monitoring for high-risk agents (isoniazid, macrolides, acitretin) 3
• After 3 months: Every 3-6 months if stable 7
• Pre-existing liver disease: More frequent monitoring required 3, 4, 8

When to Discontinue

Specific thresholds for stopping therapy 3, 4, 1:

• Persistent elevations >3x ULN warrant consideration of discontinuation 3, 4
• Serious hepatic injury with clinical symptoms, hyperbilirubinemia, or jaundice requires prompt discontinuation 4
• Patients with jaundice have approximately 10% risk of death from liver failure or need for transplantation 1

Special Populations

Patients with Cirrhosis

Prescribing requires significant modifications in decompensated cirrhosis 3, 8:

• Drugs with predominant hepatic metabolism and narrow therapeutic index should be used with caution 8
• Dose adjustments are necessary for many medications including beta-blockers (reduce by 50% when GFR <30), opioids, and sulfonylureas 3
• Idiosyncratic drug reactions occur equally in patients with normal or abnormal liver function 8

Pregnancy

Several hepatotoxic medications have specific pregnancy considerations 3:

• Acitretin: Absolutely contraindicated; women must wait 3 years after discontinuation before pregnancy 3
• Ethionamide: Teratogenic in animals; should not be used in pregnancy 3
• Colchicine: Safe during pregnancy despite concerns 3

Common Pitfalls to Avoid

• Acetaminophen and alcohol: Should be avoided during acute liver injury or when taking hepatotoxic medications 3
• Drug interactions: Carbamazepine significantly decreases levels of oral contraceptives, warfarin, and corticosteroids 7
• Delayed recognition: Some antibiotics like amoxicillin-clavulanate have delayed onset of liver injury 1
• Inadequate baseline assessment: Every effort must be made to establish the cause of abnormal LFTs and determine if cirrhosis is present before prescribing 8