How to manage elevated liver enzymes and conjugated hyperbilirubinemia?

From the Guidelines

Managing elevated liver enzymes and conjugated hyperbilirubinemia requires a comprehensive approach, including immediate discontinuation of any hepatotoxic medications and alcohol consumption, as well as supportive care to address the underlying cause and prevent progression to liver failure. The diagnostic workup should include comprehensive liver function tests, viral hepatitis serologies (HAV, HBV, HCV), autoimmune markers (ANA, ASMA, AMA), iron studies, ceruloplasmin levels, and imaging such as ultrasound or MRI of the liver and biliary system 1.

Key Considerations

• Discontinue any hepatotoxic medications and alcohol consumption immediately
• Diagnostic workup should include comprehensive liver function tests and imaging
• Consider endoscopic retrograde cholangiopancreatography (ERCP) for biliary obstruction
• Monitor liver function tests every 1-2 weeks initially, then monthly as improvement occurs

Treatment Options

• For drug-induced liver injury, N-acetylcysteine (NAC) at 140 mg/kg orally followed by 70 mg/kg every 4 hours for 17 doses may be beneficial
• For autoimmune hepatitis, prednisone 40-60 mg daily with gradual tapering and azathioprine 50-150 mg daily as maintenance therapy is often effective
• Ursodeoxycholic acid 13-15 mg/kg/day in divided doses can help in cholestatic conditions like primary biliary cholangitis

Recent Guidelines

According to the most recent guidelines, patients with cancer are at elevated risk for liver injury from a variety of causes, including hepatic metastasis, thromboembolic disease, biliary compression, perfusion injury, opportunistic infections, and drug reactions 1. Elevated alkaline phosphatase and/or bilirubin should prompt cross-sectional hepatobiliary imaging, such as CT/magnetic resonance imaging, and cross-sectional imaging may be valuable more broadly in any patient at risk for or with known hepatic metastases.

Pathophysiological Mechanism

Elevated liver enzymes and hyperbilirubinemia indicate hepatocellular damage and impaired bile excretion, respectively, so addressing the specific pathophysiological mechanism is crucial for effective management and preventing progression to liver failure 1. The fraction of direct bilirubin should be measured, and is usually greater than 35% when hyperbilirubinemia is due to DILI 1.

Monitoring and Follow-up

Monitor liver function tests every 1-2 weeks initially, then monthly as improvement occurs. Consider liver biopsy in patients with grade 2 hepatitis or higher, who may require systemic glucocorticoids or potential ICI discontinuation 1.

From the FDA Drug Label

WARNINGS Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns has been reported in patients treated with rifampin. Severity ranged from asymptomatic elevations in liver enzymes, isolated jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant liver failure and death Monitor for symptoms and clinical/laboratory signs of liver injury, especially if treatment is prolonged or given with other hepatotoxic drugs Patients with impaired liver function should be given rifampin only in cases of necessity and then under strict medical supervision. If signs of hepatic damage occur or worsen, discontinue rifampin

To manage elevated liver enzymes and conjugated hyperbilirubinemia, the following steps should be taken:

• Monitor patients for symptoms and clinical/laboratory signs of liver injury, especially if treatment is prolonged or given with other hepatotoxic drugs.
• Discontinue rifampin if signs of hepatic damage occur or worsen.
• Provide strict medical supervision for patients with impaired liver function.
• Consider liver function tests prior to therapy and every 2 to 4 weeks during therapy for patients with impaired liver function 2.

From the Research

Elevated Liver Enzymes

• Elevated liver enzymes can be caused by various factors, including statin use 3, and can be categorized into hepatocellular or cholestatic patterns based on the magnitude of aminotransferase elevation 4.
• A hepatocellular pattern is characterized by elevated aminotransferases, and can be caused by non-alcoholic fatty liver disease, alcohol use, chronic viral hepatitis, and other conditions 4.
• A cholestatic pattern is characterized by elevated alkaline phosphatase and gamma-glutamyl transferase, and can be caused by biliary pathology, autoimmune disorders, and other conditions with hyperbilirubinemia 4.

Conjugated Hyperbilirubinemia

• Conjugated hyperbilirubinemia occurs when the liver is unable to properly excrete bilirubin, and can be caused by various underlying disease states, including liver disease, biliary strictures, and choledocholithiasis 5, 6.
• Evaluation of conjugated hyperbilirubinemia should include a comprehensive medical history, review of systems, and physical examination, as well as laboratory tests such as bilirubin assays, liver function tests, and imaging studies 5, 6.
• Measuring fractionated bilirubin can help determine whether the hyperbilirubinemia is conjugated or unconjugated, and can aid in diagnosis and management 6.

Management

• Management of elevated liver enzymes and conjugated hyperbilirubinemia depends on the underlying cause, and may involve treatment of the underlying disease state, as well as monitoring of liver function and adjustment of medications as needed 3, 4.
• In some cases, liver biopsy may be required to establish the diagnosis, prognosis, and management of the disease 6.
• A diagnostic algorithm can be used to guide the evaluation and management of patients with isolated hyperbilirubinemia, and can help avoid unnecessary medical investigations 7.