Evaluation and Management of Elevated Liver Function Tests in Non-Alcoholic Patients

Introduction to Elevated Liver Function Tests

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver function tests (LFTs) in non-drinkers, accounting for approximately 26% of incidental LFT abnormalities in primary care settings and affecting 20-30% of the general population 1

The American Association for the Study of Liver Diseases recommends systematically excluding competing etiologies in the following order: non-alcoholic fatty liver disease (NAFLD), chronic viral hepatitis, drug-induced liver injury, hemochromatosis, autoimmune liver disease, Wilson's disease, and alpha-1 antitrypsin deficiency 4, 5, 6

NAFLD is the leading cause of elevated LFTs in developed countries, with a prevalence increasing to 70% with obesity and 90% with diabetes mellitus, and typically presents with mild aminotransferase elevations (<5 times upper limit) and an AST:ALT ratio <1 1, 2
Chronic viral hepatitis must be excluded through serological testing, and can present with normal or mildly elevated LFTs 4, 5, 6

Hemochromatosis should be tested with serum ferritin and transferrin saturation, and if ferritin is elevated with high transferrin saturation, testing for HFE gene mutations should be considered 4, 5, 6, 8
Autoimmune liver disease should be checked with antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), and low titers are common in NAFLD and generally clinically insignificant 4, 5, 6

The European Association for the Study of the Liver warns against assuming the magnitude of LFT elevation correlates with disease severity or prognosis, as patients with significant liver fibrosis may have normal or minimally elevated liver enzymes 7, 1
The American Association for the Study of Liver Diseases advises against relying on "normal" LFTs to exclude significant liver disease, as many patients with advanced fibrosis have liver enzymes within the normal reference range 7, 1

A detailed history should be taken, including alcohol consumption, medications, supplements, herbal products, metabolic risk factors, and family history of liver disease 9, 4, 5, 6
Laboratory testing should include hepatitis B surface antigen, hepatitis C antibody, serum ferritin, transferrin saturation, ANA, ASMA, and lipid panel 4, 5, 6, 7
Imaging with abdominal ultrasound should be used to assess for steatosis and exclude structural abnormalities 9, 4

The American College of Gastroenterology recommends calculating non-invasive fibrosis scores, such as the FIB-4 score and NAFLD Fibrosis Score, to identify patients at risk for advanced fibrosis 1, 2
Screening for metabolic comorbidities, including type 2 diabetes, cardiovascular disease, and metabolic syndrome, should be performed in all NAFLD patients 9, 5, 1, 8

A NAFLD pattern is characterized by an AST:ALT ratio <1, mild aminotransferase elevations, and the presence of metabolic risk factors 1, 3
An alcoholic liver disease pattern is characterized by an AST:ALT ratio >2, elevated GGT, and consideration of additional biomarkers if suspicion remains 1, 3