What is the cause of elevated liver enzymes and bilirubin in this patient?

From the Guidelines

The cause of elevated liver enzymes and bilirubin in this patient is likely hepatocellular injury, given the significant elevation of ALT and AST, with a possible contribution from dehydration as suggested by hyperalbuminemia. The patient's laboratory results show a marked increase in ALT (57-358 U/L) and AST (28-279 U/L), which are indicative of hepatocellular damage, as these enzymes are concentrated in the liver and their elevations are suggestive of liver injury 1. The pattern of elevation, with ALT being more significantly elevated than AST, further supports hepatocellular injury.

Other possibilities, such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, or biliary obstruction, cannot be ruled out without further evaluation. The elevation of alkaline phosphatase (44-52 U/L) and gamma-glutamyl transferase (30-75 U/L) may suggest a cholestatic component, but these elevations are not as pronounced as those of ALT and AST.

To determine the exact cause, the patient should undergo a comprehensive evaluation, including a detailed medication history to assess for potential drug-induced liver injury (DILI), viral hepatitis serologies, autoimmune markers, and imaging studies such as ultrasound or CT scan 1. The timing of medication use relative to enzyme elevation is crucial for diagnosing DILI, with most cases showing improvement after discontinuation of the offending agent.

Given the patient's hyperalbuminemia, dehydration is a possible contributing factor, as suggested by the comment that dehydration is a possible cause of the observed hyperalbuminemia, and further clinical correlation is recommended. However, the primary concern based on the laboratory findings is hepatocellular injury, and the evaluation should prioritize identifying the cause of this injury to guide appropriate management and prevent potential progression to more severe liver disease.

From the Research

Possible Causes of Elevated Liver Enzymes and Bilirubin

• The patient's elevated liver enzymes (ALT: 57-358 U/L, AST: 28-279 U/L) and bilirubin (7-12 umol/L) may be caused by various factors, including fatty liver, alcohol-related liver damage, and chronic viral hepatitis, as these are common causes of abnormal liver function test results in asymptomatic patients 2.
• Other possible causes of asymptomatic liver disease include hemochromatosis, Wilson's disease, drug toxicity, chronic autoimmune hepatitis, biliary cirrhosis, sclerosing cholangitis, alpha1-antitrypsin deficiency, and sarcoidosis 2.
• The elevation in serum bilirubin may indicate global liver dysfunction and a high risk of liver failure, but it can also be caused by inhibition of specific enzymes/transporters by certain drugs 3.

Diagnostic Approach

• The most efficient screening tests for liver damage are alanine transaminase, alkaline phosphatase, and bilirubin, and repeat testing when results are abnormal, and use of ancillary tests, such as creatine phosphokinase or gamma-glutamyl-transferase, may confirm liver damage 2.
• Imaging studies can help exclude biliary obstruction or neoplasm, and treatable illnesses should be ruled out 2.
• A biochemical signature with higher ALT and ALT/AST ratio, a history of prior immunotherapy exposure, and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity 4.
• Liver biopsy can be safely deferred in most patients, and a non-invasive investigation can establish the cause of enzyme elevation in most patients 4.

Specific Conditions

• Primary biliary cirrhosis (stage I) can be treated with ursodeoxycholic acid, which can lead to a serological remission and a marked histological improvement 5.
• Immune checkpoint inhibitors (ICI) can cause liver enzyme elevation, which is often attributed to disease progression, other drugs/toxins, or other causes, but can also be caused by ICI immunotoxicity 4.
• The pattern of enzyme elevations, i.e., hepatocellular or cholestatic, should be used to guide the evaluation of asymptomatic patients with persistent elevation of liver enzyme levels 6.