What are the causes of elevated Alanine Transaminase (ALT)?

From the Guidelines

Elevated ALT is primarily caused by liver damage or injury, with the most common causes including viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease (NAFLD), as well as medications, autoimmune hepatitis, and other conditions. The causes of elevated ALT can be categorized into several groups, including:

• Hepatocellular injury, which can be caused by viral hepatitis, alcoholic liver disease, NAFLD, and other conditions, leading to the release of ALT and AST into the serum 1
• Medications, such as certain antibiotics, statins, anti-seizure medications, and acetaminophen, which can cause ALT elevation 1
• Autoimmune hepatitis, hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency, which are less common causes of elevated ALT 1
• Physical trauma to the liver, such as from accidents or surgery, which can temporarily raise ALT levels 1
• Muscle disorders or intense exercise, which can also elevate ALT since this enzyme is present in muscle tissue as well as the liver 1 The severity of elevation often correlates with the degree of liver damage, with mild elevations (less than 5 times normal) may indicate chronic conditions like NAFLD, while dramatic elevations (greater than 10 times normal) typically suggest acute viral hepatitis or drug-induced liver injury 1. When ALT is elevated, further testing is usually needed to determine the specific cause, which may include additional blood tests, imaging studies, or sometimes liver biopsy 1.

Some key points to consider when evaluating elevated ALT include:

• The AST:ALT ratio, which can help differentiate between alcoholic liver disease and other causes of liver injury 1
• The presence of other liver enzymes, such as ALP, which can indicate cholestatic liver disease 1
• The patient's medical history, including any history of liver disease, medication use, or other conditions that may affect the liver 1
• The use of noninvasive tests, such as transient elastography, to evaluate fibrosis status in patients with chronic HBV infection 1

Overall, the evaluation and management of elevated ALT require a comprehensive approach that takes into account the patient's medical history, physical examination, laboratory results, and other factors to determine the underlying cause and develop an effective treatment plan.

From the Research

Causes of Elevated Alanine Transaminase (ALT)

Elevated Alanine Transaminase (ALT) levels can be caused by various factors, including:

• Liver diseases such as non-alcoholic fatty liver disease (NAFLD) 2, hepatitis B 2, hepatitis C 2, 3, autoimmune hepatitis 2, 3, and alcoholic hepatitis 2, 3
• Extrahepatic conditions such as muscle damage 4
• Metabolic disorders like diabetes 3
• Genetic disorders such as hemochromatosis 3 and alpha 1-anti-trypsin deficiency 3
• Drug-induced liver injury 3, 5
• Ischemic hepatitis 5
• Acute viral hepatitis 5
• Overweight and obesity 3
• Alcohol consumption 3, 6

Specific Causes and Their Frequencies

According to the studies, the frequencies of these causes vary:

• NAFLD was the most common cause of persistently elevated serum ALT levels in one study, accounting for 55% of cases 2
• Obesity and alcoholism were the most frequently associated factors with ALT elevation in another study, accounting for 30.2% and 28.6% of cases, respectively 3
• Acetaminophen toxicity, ischemic hepatitis, and acute viral hepatitis were found to be common causes of severe acute liver injury in a multicenter study 5

Association with Alcohol Consumption

Alcohol consumption has been shown to be associated with elevated ALT levels:

• Even small amounts of alcohol intake were found to be harmful in individuals with elevated ALT levels, increasing the risk of liver-related and all-cause mortality 6
• Alcoholism was a common cause of ALT elevation in several studies 2, 3