From the Guidelines
Elevated Liver Function Tests (LFTs) can be caused by various factors including viral hepatitis, alcohol consumption, non-alcoholic fatty liver disease, medications, autoimmune conditions, and metabolic disorders, as evident from recent studies 1. The causes of elevated LFTs can be broadly categorized into hepatocellular and cholestatic patterns. Hepatocellular patterns, characterized by elevated AST/ALT, suggest liver cell damage and can be seen in conditions such as viral hepatitis, alcohol-induced liver disease, and non-alcoholic fatty liver disease 1. On the other hand, cholestatic patterns, marked by elevated alkaline phosphatase and GGT, indicate bile flow problems and can be caused by conditions such as gallstones, biliary obstruction, and primary biliary cholangitis 1. Some key points to consider when evaluating elevated LFTs include:
- A thorough history, including medication use, alcohol consumption, and risk factors for viral hepatitis, is essential for diagnosis 1
- Additional testing, such as hepatitis serologies, ultrasound, or liver biopsy, may be necessary to determine the underlying cause of elevated LFTs 1
- The pattern of LFT abnormalities can provide clues to the underlying cause, with hepatocellular patterns suggesting liver cell damage and cholestatic patterns indicating bile flow problems 1
- Other causes of elevated LFTs, such as infections, genetic conditions, and metabolic disorders, should also be considered in the differential diagnosis 1 It is also important to note that the management of elevated LFTs depends on the underlying cause and may involve treatment of the underlying condition, as well as monitoring of liver function tests to prevent further liver damage 1.
From the FDA Drug Label
Among entecavir-treated subjects in these studies, on-treatment ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline generally resolved with continued treatment. A majority of these exacerbations were associated with a ≥2 log 10/mL reduction in viral load that preceded or coincided with the ALT elevation
- Elevated Liver Function Tests (LFTs), specifically ALT elevations, can be caused by:
- Viral load reduction: A majority of ALT elevations were associated with a ≥2 log 10/mL reduction in viral load that preceded or coincided with the ALT elevation 2
- Hepatitis exacerbation: Exacerbations of hepatitis or ALT flares were defined as ALT greater than 10 times ULN and greater than 2 times the subject’s reference level 2
- Periodic monitoring of hepatic function is recommended during treatment 2
From the Research
Causes of Elevated Liver Function Tests (LFTs)
Elevated LFTs can be caused by various factors, including:
- Hepatocellular damage, which can be indicated by elevated levels of certain enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3, 4
- Cholestatic derangement, which can be indicated by elevated levels of alkaline phosphatase and gamma-glutamyl transferase 5
- Metabolic-associated fatty liver disease (MAFLD), which is the most common cause of abnormal LFTs 4
- Acute hepatic dysfunction, acute liver failure, and drug-induced liver injury, which are common causes of elevated LFTs in the intensive care unit (ICU) 6
- Nonalcoholic fatty liver disease (NAFLD), which can present with different patterns of elevated LFTs, including hepatocellular, cholestatic, and mixed patterns 7
Patterns of Elevated LFTs
Different patterns of elevated LFTs can indicate different underlying conditions, such as:
- Hepatocellular pattern, which is characterized by elevated levels of ALT and AST 3, 7
- Cholestatic pattern, which is characterized by elevated levels of alkaline phosphatase and gamma-glutamyl transferase 5, 7
- Mixed pattern, which is characterized by elevated levels of both hepatocellular and cholestatic enzymes 7
Clinical Significance of Elevated LFTs
Elevated LFTs can be associated with increased mortality, particularly in critically ill patients 6. Additionally, the pattern of elevated LFTs can predict the degree of liver fibrosis and metabolic-associated comorbidities in patients with NAFLD 7. Therefore, comprehensive diagnostic evaluation is essential to identify the underlying etiology of abnormal LFTs and to initiate appropriate therapeutic strategies 6.