From the Guidelines
Elevated liver function tests (LFTs) are most commonly caused by nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease, with other causes including viral hepatitis, medication-induced liver injury, and autoimmune hepatitis. The pattern of LFT elevation can provide diagnostic clues, with hepatocellular patterns (elevated AST/ALT) suggesting direct liver cell damage, and cholestatic patterns (elevated alkaline phosphatase/GGT) indicating bile flow problems 1.
Common Causes of Elevated LFTs
- Nonalcoholic fatty liver disease (NAFLD)
- Alcohol-induced liver disease
- Viral hepatitis (hepatitis A, B, C, D, and E)
- Medication-induced liver injury
- Autoimmune hepatitis
Less Common Causes of Elevated LFTs
- Hemochromatosis
- Wilson's disease
- Alpha-1 antitrypsin deficiency
- Liver malignancies
- Biliary obstruction
Diagnostic Approach
When evaluating elevated LFTs, it's essential to consider the patient's complete medical history, medication use, alcohol consumption, and risk factors for viral hepatitis 1. Initial workup typically includes:
- Hepatitis serologies
- Autoimmune markers
- Iron studies
- Imaging of the liver and biliary system The AST:ALT ratio can help differentiate between alcohol-induced and nonalcoholic fatty liver disease, with a ratio >2 suggesting alcohol-induced liver disease and a ratio <1 suggesting nonalcoholic fatty liver disease 1.
From the Research
Causes of Elevated LFTs
Elevated liver function tests (LFTs) can be caused by various factors, including:
- Viral hepatitis B and C infections, which can lead to liver inflammation and damage 2, 3, 4
- Non-alcoholic fatty liver disease (NAFLD), a condition characterized by excessive fat accumulation in the liver, which can progress to non-alcoholic steatohepatitis (NASH) and cirrhosis 5, 3, 4
- Metabolic dysfunction-associated fatty liver disease (MAFLD), a condition associated with insulin resistance, metabolic syndrome, and liver fat accumulation 2
- Alcoholic liver disease (ALD), which can cause liver inflammation and damage due to excessive alcohol consumption 2
- Coexistence of multiple liver diseases, such as MAFLD and viral hepatitis, or NAFLD and hepatitis C, which can lead to more severe liver damage and progression to cirrhosis 2, 3, 4
Patterns of Elevated LFTs
The pattern of elevated LFTs can provide clues about the underlying cause of liver damage, including:
- Hepatocellular pattern (H pattern), characterized by elevated hepatocellular enzymes, which is commonly seen in NAFLD patients 5
- Cholestatic pattern (C pattern), characterized by elevated cholestatic enzymes, which is associated with advanced fibrosis and metabolic-associated comorbidities in NAFLD patients 5
- Mixed pattern (M pattern), characterized by a combination of hepatocellular and cholestatic enzymes, which is also seen in NAFLD patients 5
Risk Factors for Elevated LFTs
Certain risk factors can increase the likelihood of developing elevated LFTs, including:
- Obesity and metabolic syndrome, which are associated with insulin resistance and liver fat accumulation 3, 4
- Diabetes and hypertension, which are commonly seen in patients with NAFLD and MAFLD 5, 3
- Family history of liver disease, which can increase the risk of developing viral hepatitis and NAFLD 6
- Lack of awareness and screening for liver diseases, which can lead to delayed diagnosis and treatment 6