What are the implications of persistently elevated Liver Function Tests (LFTs)?

From the Guidelines

Persistently elevated liver function tests (LFTs) should be managed by identifying and addressing the underlying cause, with a focus on discontinuing potential hepatotoxic medications, lifestyle modifications for non-alcoholic fatty liver disease (NAFLD), and antiviral therapy for viral hepatitis, as recommended by the most recent guidelines 1.

Initial Evaluation

The initial evaluation of persistently elevated LFTs should include a complete medical history, physical examination, and additional testing to identify common causes such as:

• Alcohol use
• Medications (e.g., statins, antibiotics, and NSAIDs)
• NAFLD
• Viral hepatitis (B and C)
• Autoimmune hepatitis
• Metabolic disorders

Management

Initial management involves:

• Discontinuing potential hepatotoxic medications and alcohol consumption
• Lifestyle modifications for NAFLD, including weight loss, regular exercise, and a balanced diet
• Antiviral therapy for viral hepatitis, such as entecavir or tenofovir for hepatitis B, and direct-acting antivirals for hepatitis C
• Immunosuppressive therapy with prednisone and azathioprine for autoimmune hepatitis

Monitoring and Referral

Regular monitoring of LFTs every 3-6 months is essential to track progress, and prompt referral to a hepatologist is warranted if LFTs continue to worsen despite intervention, or if there are signs of advanced liver disease (jaundice, ascites, encephalopathy) 1.

Key Considerations

• The management of persistently elevated LFTs should be guided by the most recent guidelines and should prioritize the identification and treatment of the underlying cause.
• A thorough evaluation and monitoring are crucial to prevent progressive liver damage and liver failure.
• The use of immunosuppressive therapy, such as corticosteroids, should be considered in cases of autoimmune hepatitis or immune-mediated liver injury, as recommended by recent guidelines 1.

From the Research

Causes of Persistently Elevated LFT

• Nonalcoholic fatty liver disease, which can affect up to 30 percent of the population 2
• Alcoholic liver disease, medication-associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis 2
• Less common causes include α(1)-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 2
• Extrahepatic conditions such as thyroid disorders, celiac disease, hemolysis, and muscle disorders can also cause elevated liver transaminase levels 2

Evaluation of Elevated LFT

• A stepwise evaluation should be initiated based on the prevalence of diseases that cause mild elevations in transaminase levels 2
• Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepatitis B surface antigen and hepatitis C virus antibody testing 2
• If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate 2

Management of Elevated LFT

• In patients with abnormal LFTs, every effort must be made to establish the cause of the abnormal liver function 3
• Whether the patient has cirrhosis also needs to be determined, as this will have broad reaching implications for prescribing 3
• In advanced liver disease, drugs with predominant hepatic metabolism and/or excretion, particularly those with a narrow therapeutic index, should be used with caution 3
• The development of LFT abnormalities while on posaconazole therapy may not warrant a switch to an alternative, potentially less effective antifungal, as hepatotoxicity is often multifactorial and generally resolves with time in the majority of patients 4

Clinical Approach to Elevated LFT

• The liver is a complex organ with multiple roles, and the key biochemical markers of hepatic function can be organized into the groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles 5
• Pathologic alterations to these markers can be algorithmically assessed by separating disease processes of these groupings, followed by assessment of the magnitude of enzymatic elevation 5
• An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis, and this may assist providers in ensuring appropriate management and evaluation of the patient with elevated LFTs 5