What is the next step for a patient with mild elevated liver enzymes?

From the Guidelines

The next step for a patient with mild elevated liver enzymes is to monitor patient for abnormal liver blood tests and review medications and supplements that may cause hepatotoxicity, as no treatment is recommended for grade 1 LFT abnormality. Specifically:

• Monitor patient for abnormal liver blood tests: AST, ALT, and bilirubin before each infusion and/or consider weekly if grade 1 LFT elevations 1.
• Review medications and supplements that may cause hepatotoxicity and rule out abnormal liver enzymes from development or progression of liver metastases 1.
• Consider testing for common causes of liver disease, such as viral hepatitis, alcohol history, iron studies, thromboembolic event, or potential liver metastasis from primary malignancy by doing blood work and imaging (ultrasound and cross-sectional imaging) 1.
• If suspicion for primary autoimmune hepatitis is high, can consider ANA/ASMA/ANCA, and if patients with elevated ALKP alone, GGT should be tested 1.
• For isolated elevation of transaminases, consider checking CK for other etiologies 1. This approach allows time for transient elevations to resolve while actively investigating potential causes, and is supported by the most recent guidelines, including the 2021 ASCO guideline update 1 and the 2020 Journal of Autoimmunity study 1.

From the Research

Next Steps for Patients with Mild Elevated Liver Enzymes

The next steps for a patient with mild elevated liver enzymes involve a thorough evaluation to determine the underlying cause of the elevation.

• A comprehensive history should be taken, including the use of medications, vitamins, herbs, drugs, and alcohol, as well as family history and any history of blood-product transfusions 2.
• Initial serologic evaluation should include liver chemistries, prothrombin time, albumin, complete blood count with platelets, hepatitis A, B, and C serologies, and iron studies 2.
• Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity 2.
• If elevations persist after an appropriate period of observation, further testing may include ultrasonography and other serum studies, and in some cases, biopsy may be indicated 2.

Potential Causes of Liver Transaminase Elevations

Potential causes of liver transaminase elevations include:

• Viral hepatitis
• Alcohol use
• Medication use
• Steatosis or steatohepatitis
• Cirrhosis
• Other common health conditions, such as diabetes, heart disease, and thyroid disease, can also cause or augment liver transaminase elevations 2.
• Pancreaticobiliary causes, such as recurrent choledocholithiasis, should be considered in the workup of severe transaminitis, even in patients with a remote history of cholecystectomy 3.
• Non-hepatitis viruses, such as Epstein-Barr and dengue virus, can cause severe transaminitis in returning travelers 4.
• Drug-induced liver injury, such as that caused by labetalol, is a common cause of transaminitis in pregnancy and postpartum period 5.

Importance of Transaminases in Clinical Practice

Transaminases, including serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are indicators of hepatocellular injury and their increase requires further investigations 6.

• The normal ALT level ranges from 29 to 33 IU/L in males and 19 to 25 IU/L in females 6.
• Elevated ALT levels have been associated with increased liver-related mortality 6.
• The investigations imposed by a high level of transaminases include testing for viral hepatitis, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for autoimmune hepatitis, hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency, as well as exclusion of hepatotoxic drugs consumption 6.