What does it mean when Alkaline Phosphatase (ALP) and Alanine Transaminase (ALT) are elevated?

From the Guidelines

Elevated alkaline phosphatase (ALP) and alanine transaminase (ALT) levels are indicative of liver dysfunction or disease, suggesting hepatocellular damage or cholestatic liver disease, as noted in the 2023 study by the Journal of the American College of Radiology 1. The elevation of these enzymes can be caused by various factors, including viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, medication-induced liver injury, and biliary obstruction.

• The pattern of elevation is crucial in determining the type of liver problem, with ALT being more specific to liver cell damage, and ALP elevations often suggesting bile duct issues, as seen in cholestatic liver disease 1.
• The degree of elevation also matters, with mild increases potentially indicating less severe conditions, and dramatic elevations signaling acute liver injury, which can be classified as mild, moderate, or severe based on the severity of abnormal aminotransferase 1. Key points to consider include:
• Normal ALT levels are 29 to 33 IU/L (0.48-0.55 mkat/L) in men and 19 to 25 IU/L (0.32-0.42 mkat/L) in women, and any elevation above these levels may indicate liver damage 1.
• Additional testing is typically needed to determine the underlying cause of elevated liver enzymes, including other liver enzymes, bilirubin levels, viral hepatitis panels, and possibly imaging studies or liver biopsy.
• If you have elevated liver enzymes, it is essential to avoid alcohol, review medications with your doctor, and follow up with appropriate testing to determine the underlying cause and prevent further liver damage, as recommended by the 2023 study 1.

From the Research

Elevated Alk Phos and ALT

Elevated levels of alkaline phosphatase (Alk Phos) and alanine aminotransferase (ALT) in liver chemistries can indicate liver damage or disease. The following points summarize the implications of these elevations:

• Hepatocellular injury is defined as a disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 2.
• Cholestatic injury is defined as a disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 2.
• An elevated ALT level has been associated with increased liver-related mortality, and a true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females 2.
• The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation of liver disease 2.

Possible Causes

Possible causes of elevated Alk Phos and ALT levels include:

• Hepatocellular disease, such as viral hepatitis A, B, and C, nonalcoholic fatty liver disease, and alcoholic liver disease 2.
• Cholestatic disease, such as primary biliary cholangitis and primary sclerosing cholangitis 2.
• Other conditions, such as hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2.
• Medication-induced liver injury, as a history of prescribed and over-the-counter medicines should be sought 2.

Diagnostic Approach

The diagnostic approach for elevated Alk Phos and ALT levels includes:

• Fractionation of total bilirubin elevation to direct and indirect bilirubin fractions, as an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings 2.
• Serologic testing for viral hepatitis, autoimmune hepatitis, and other conditions 2.
• Imaging studies to evaluate liver morphology and function 2.
• Liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2.