From the Guidelines
Transaminitis is primarily caused by hepatocellular injury, which can be attributed to various conditions, including nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, viral hepatitis, and medications/toxins, as evidenced by the most recent study 1. The causes of transaminitis can be categorized into common, uncommon, and rare causes.
- Common causes include NAFLD and alcohol-induced liver disease, which are the two most common causes of fatty liver disease.
- Uncommon causes comprise drug-induced liver injury, hepatitis B, hepatitis C, and hereditary hemochromatosis.
- Rare causes are alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease, as noted in the study 1. The pattern of enzyme elevation can provide clues to the underlying cause, with hepatocellular predominant liver chemistry characterized by elevated aminotransferases, particularly ALT, which is directly linked to hepatocyte injury 1. It is essential to consider nonhepatic causes, such as hemolysis, myopathy, thyroid disease, and exercise, when the aminotransferase rise is predominantly AST, as mentioned in the study 1. The AST:ALT ratio can also help differentiate between alcohol-induced fatty liver disease (generally >2) and metabolic disease-related fatty liver (generally <1), as reported in the study 1. Overall, a thorough understanding of the causes of transaminitis and the pattern of enzyme elevation is crucial for proper diagnosis and management, as emphasized by the recent study 1.
From the FDA Drug Label
WARNINGS Liver warning: This product contains acetaminophen. Severe Liver damage may occur if you take • more than 6 caplets in 24 hours, which is the maximum daily amount • with other drugs containing acetaminophen • 3 or more alcoholic drinks everyday while using this product Ask a doctor before use if you have liver disease.
The causes of transaminitis (or liver damage) mentioned in the label are:
- Taking more than 6 caplets in 24 hours
- Taking the product with other drugs containing acetaminophen
- Consuming 3 or more alcoholic drinks everyday while using the product
- Having liver disease 2 2
From the Research
Causes of Transaminitis
- The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease 3
- Uncommon causes include drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis 3
- Rare causes include alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 3
- Extrahepatic sources, such as thyroid disorders, celiac sprue, hemolysis, and muscle disorders, are also associated with mildly elevated transaminase levels 3
Severe Acute Liver Injury
- The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often includes ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury (DILI) 4
- A multicenter study found that the most common causes of acute liver injury (ALI) with an ALT and/or AST level ≥1000 IU/L are not well established, and more research is needed to determine the relative frequencies of different etiologies 4
Evaluation of Abnormal Liver Chemistries
- Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 5
- Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 5
- The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 5