From the Guidelines
Elevations in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) levels are indicative of liver damage or disease, with the pattern of elevation helping to determine the cause, such as hepatocellular injury or cholestatic conditions, as noted in the most recent study 1.
Causes of Elevations
The causes of elevations in these liver enzymes can be varied, including:
- Hepatocellular injury, which can be caused by conditions such as hepatitis, fatty liver disease, or medication toxicity, as seen in 1 and 1
- Cholestatic conditions, which can be caused by bile duct obstruction or other liver diseases, as noted in 1 and 1
- Non-hepatic causes, such as heart attack or muscle injury, which can cause elevations in AST, as mentioned in 1 and 1
Interpretation of Test Results
When interpreting these test results, it's essential to consider the patient's complete clinical picture, including symptoms, medical history, and other laboratory findings, as emphasized in 1 and 1. The ratio of AST to ALT can also provide clues, with AST:ALT >2 suggesting alcoholic liver disease, while viral hepatitis typically shows higher ALT than AST, as noted in 1 and 1.
Clinical Implications
The clinical implications of elevations in these liver enzymes can be significant, with potential consequences including liver damage, disease, or even failure, as seen in 1 and 1. Therefore, it's crucial to promptly evaluate and manage patients with abnormal liver function tests to prevent or minimize these consequences, as recommended in 1 and 1.
From the FDA Drug Label
The most common adverse events (at least 20%) for SOVALDI + ribavirin combination therapy were fatigue and headache The most common adverse events (at least 20%) for SOVALDI + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia and anemia Table 4 Adverse Events (All Grades and without Regard to Causality) Reported in ≥15% of Subjects with HCV in Any Treatment Arm Less Common Adverse Reactions Reported in Clinical Trials (less than 1%): Laboratory Abnormalities: Changes in selected hematological parameters are described in Table 5.
The FDA drug label does not answer the question.
From the Research
Implications of Elevated Liver Enzymes
Elevations in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) levels can have significant implications for patient health. The causes of these elevations can be varied, and it is essential to investigate and manage them appropriately.
Causes of Elevated Liver Enzymes
The causes of elevated liver enzymes can be categorized into several groups, including:
- Hepatic diseases, such as chronic hepatitis B and C, autoimmune hepatitis, non-alcoholic steatohepatitis, hemochromatosis, and Wilson's disease 2
- Cholestatic patterns, such as primary biliary cirrhosis, primary sclerosing cholangitis, and drug-induced cholestasis 2
- Non-alcoholic fatty liver disease (NAFLD), which is the most common cause of transaminase elevation, followed by alcohol intake and hepatitis C virus infection 3
- Immunotoxicity, which can occur in patients treated with immune checkpoint inhibitors, and is associated with higher peak ALT and ALT:AST ratio 4
Evaluation of Elevated Liver Enzymes
The evaluation of elevated liver enzymes should involve a step-wise approach, starting with non-invasive serologic tests and imaging studies, such as ultrasound and liver biopsy if necessary 2, 3, 5, 6. The goal of evaluation is to establish a definitive diagnosis and guide management.
Key Findings
- Elevated liver enzymes are common in patients receiving immune checkpoint inhibitors, but often have a cause other than immunotoxicity 4
- A biochemical signature with higher ALT and ALT:AST ratio, a history of prior ICI 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 with elevated liver enzymes 4
- Extensive evaluation of all abnormal liver enzyme tests would expose many patients to undue risks and expenses, but failure to evaluate minor liver enzyme elevations could mean missing the early diagnosis of potentially treatable disorders 5, 6