Non-alcoholic fatty liver disease laboratory findings

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2] Parth Vikram Singh, MBBS[3]

There are no specific diagnostic laboratory findings associated with non alcoholic fatty liver disease. Laboratory findings include abnormal liver function tests but are unspecific. Other laboratory tests are generally performed to rule out other diagnosis.

• There is no specific laboratory findings diagnostic for non alcoholic fatty liver disease.^[1][2]
• Liver function tests
  • Typical finding include a 2-4 fold elevation of the ALT 
  • An ALT/AST ratio of greater than 1.
  • Normal aminotransferase levels do not exclude MASLD, advanced fibrosis, or cirrhosis. Up to two-thirds of patients with MASLD, including patients with advanced fibrosis or cirrhosis, may have normal serum aminotransferase levels, and serum ALT levels do not correlate well with histological severity.^[3]

• Evaluation for alternative causes of liver disease should be performed.
  • These include HCV serology, serologies for autoimmune hepatitis, and copper studies including serum ceruloplasmin and 24-hour urinary copper if Wilson disease is suspected.

• Laboratory evaluation should include assessment of metabolic risk factors. Fasting plasma glucose testing following an overnight fast is important to look for hyperglycemia, which is an indicator of insulin resistance.
  • Fasting insulin levels can confirm hyperinsulinemia and insulin resistance
• Lipid levels ( serum cholesterol and fasting triglycerides ) should be evaluated
  • Dyslipidemia, beside being a very common finding in NAFLD, is a risk factor that can be modified by dietary and/or pharmacologic intervention.
• Iron studies (in particular elevated ferritin and transferring saturation) are often abnormal in NAFLD
• Some patients with NAFLD may have low titers of autoimmune antibodies.
• Noninvasive fibrosis assessment commonly includes the Fibrosis-4 index and the enhanced liver fibrosis test.
  • The Fibrosis-4 index includes age, serum alanine aminotransferase level, serum aspartate aminotransferase level, and platelet count. It estimates the risk of advanced liver fibrosis as low when the score is less than 1.30, indeterminate when the score is 1.30 to 2.67, and high when the score is greater than 2.67. A Fibrosis-4 index less than 1.3 has a negative predictive value of 85% to 90% for detecting advanced liver fibrosis.

• Biomarkers
  • CK18 represents a promising biomarker for evaluation of the presence of NASH.
  • A defining characteristic of NASH is cellular death, and serum CK18 levels had been shown to correlate with steatohepatitis.

Non-alcoholic fatty liver disease, especially if with cirrhosis, may be associated with thrombocytopenia^[4][5].

A fibrosis score can be obtained via:

• Liver biopsy. Various scoring systems exist including the Ishak; however, Ishak deems cirrhosis at a score of 5 or 6^[6].
  • F0. No fibrosis
  • F1. Fibrous portal expansion
  • F2. Few septa
  • F3. Bridging fibrosis. Numerous septa
  • F4. Cirrhosis
• The enhanced liver fibrosis test uses tissue inhibitor of metalloproteinase 1, type III procollagen amino terminal peptide, and hyaluronic acid to generate a fibrosis severity score. The enhanced liver fibrosis test has a sensitivity of approximately 98% for detecting advanced liver fibrosis.
• The Agile 3+ score combines liver stiffness measured by vibration-controlled transient elastography with aspartate aminotransferase to alanine aminotransferase ratio, platelet count, diabetes status, sex, and age. It may identify advanced fibrosis more accurately than the Fibrosis-4 index or liver stiffness measurement alone.
• Nonivasive serological liver fibrosis score such as AST to platelet ratio (APRI), and proprietary tests such as: FibroTest, FibroSure, Hepascore, and FibroSpect. An example is based on the “serum hyaluronic acid, procollagen type III N-terminal peptide, and tissue inhibitor of metalloproteinase 1”^[7].
  • A score > “9.8 indicates a moderate risk of advanced fibrosis”<ref name=”pmid33185364”>/
  • A score > “11.3 denotes a high risk of advanced fibrosis”^[7]
• Noninvasive imaging scores such as the Fibroscan.

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