What causes liver function derangement in bronchiectasis?

Causes of Liver Function Derangement in Bronchiectasis

The primary causes of liver function derangement in bronchiectasis are medication-related hepatotoxicity, systemic inflammation, and underlying disorders that predispose to both bronchiectasis and liver abnormalities.

Medication-Related Causes

• Long-term antibiotic therapy used to treat chronic bronchial infections in bronchiectasis can cause drug-induced liver injury, particularly with macrolides, which are commonly used for their anti-inflammatory properties 1
• Medications used during exacerbations, including high-dose antibiotics like lopinavir-ritonavir, can increase ALT to >5 times upper limit of normal in approximately 5% of patients 1
• Remdesivir, which may be used in severe respiratory infections, can cause mild ALT elevation to >2 times upper limit of normal and moderate AST elevation 1
• Tocilizumab, sometimes used for severe inflammatory states, causes ALT elevation in >20% of patients and can increase ALT to >5 times upper limit of normal in <1% of patients 1

Inflammatory Mechanisms

• Chronic bronchial infection in bronchiectasis leads to persistent systemic inflammation mediated by neutrophils, T lymphocytes, and monocyte-derived cytokines 1
• This systemic inflammatory response can affect the liver, causing elevation in liver enzymes similar to what is seen in other inflammatory conditions 1
• Exacerbations of bronchiectasis are associated with increased airways and systemic inflammation that may contribute to liver function abnormalities 1

Underlying Disorders Associated with Both Bronchiectasis and Liver Disease

• Alpha-1-antitrypsin deficiency is listed as a predisposing factor for bronchiectasis and can also cause liver disease 1
• Inflammatory bowel disease is associated with both bronchiectasis and liver abnormalities including primary sclerosing cholangitis 1
• Rheumatoid arthritis can predispose to bronchiectasis and is also associated with autoimmune liver disease 1

Infection-Related Mechanisms

• Chronic bacterial infections with organisms like Pseudomonas aeruginosa can lead to sepsis-like states during exacerbations, potentially causing liver dysfunction 1
• Patients with bronchiectasis are at higher risk of recurrent infections that can lead to sepsis-associated cholestasis 1
• Hypoxemia during severe exacerbations can cause ischemic hepatitis, contributing to liver function derangement 1

Nutritional Factors

• Malnutrition is common in severe bronchiectasis and can contribute to liver dysfunction 2
• A case report showed increased liver enzymes (AST 206U/L, ALT 224U/L) in a patient with infected bronchiectasis who had poor nutritional status 2
• Nutritional therapy with adequate macro and micronutrients improved liver enzyme levels in this patient 2

Clinical Approach to Liver Derangement in Bronchiectasis

• Monitor liver function tests in patients on long-term antibiotic therapy, particularly those on macrolides or during exacerbation treatment 1
• Consider screening for underlying conditions that can cause both bronchiectasis and liver disease, particularly in patients with diffuse bronchiectasis 1
• Evaluate for drug-induced liver injury when new medications are introduced, especially during treatment of exacerbations 1
• Assess nutritional status in patients with bronchiectasis who develop liver function abnormalities 2

Management Considerations

• When liver function derangement occurs, evaluate the medication regimen and consider alternatives with lower hepatotoxicity potential 1
• Address nutritional deficiencies through appropriate nutritional therapy, which may improve both liver function and overall outcomes 2
• For patients with underlying conditions like alpha-1-antitrypsin deficiency, coordinate care with hepatology 1
• During exacerbations requiring intensive treatment, closely monitor liver function and adjust medications as needed 1

Remember that liver function derangement in bronchiectasis is often multifactorial, with contributions from medications, systemic inflammation, hypoxemia during exacerbations, and potentially underlying disorders that predispose to both conditions.