Laboratory Evaluation for Suspected Nonalcoholic Cirrhosis

Core Laboratory Panel

The American Gastroenterological Association recommends a baseline liver evaluation including complete blood count, comprehensive liver panel, INR, creatinine, albumin, and prothrombin time, along with tests to exclude alternative causes of liver disease 1, 2
The European Association for the Study of the Liver suggests essential hepatic function tests, including complete metabolic panel with liver enzymes, such as AST, ALT, bilirubin, and alkaline phosphatase 1, 2, 3
Synthetic function markers, such as serum albumin, prothrombin time, or INR, are recommended by the American Association for the Study of Liver Diseases to assess liver function 1, 4
A complete blood count is necessary to evaluate for thrombocytopenia, which suggests portal hypertension, as recommended by the European Association for the Study of the Liver 4
Serum creatinine is used to assess renal function, as suggested by the American College of Gastroenterology 1

An AST > ALT ratio suggests more advanced fibrosis or cirrhosis, according to the American Association for the Study of Liver Diseases 1, 2
Thrombocytopenia, indicated by a platelet count <150,000, suggests portal hypertension and likely cirrhosis, as recommended by the European Association for the Study of the Liver 1, 4
Hypoalbuminemia, or low albumin, suggests decreased synthetic function and advanced disease, according to the American Gastroenterological Association 1, 2
Elevated INR or prolonged prothrombin time indicates impaired hepatic synthetic capacity, as suggested by the American Association for the Study of Liver Diseases 4

Fasting glucose and/or hemoglobin A1c should be assessed to evaluate for diabetes, a major risk factor for NASH and advanced fibrosis, as recommended by the American Diabetes Association 1, 2
Lipid profile should be evaluated to assess dyslipidemia as part of metabolic syndrome, according to the American Heart Association 1, 2
Body mass index and waist circumference should be documented to assess obesity parameters, as suggested by the World Health Organization 1, 2

Hepatitis B surface antigen should be tested to exclude chronic hepatitis B, as recommended by the Centers for Disease Control and Prevention 4, 5
Hepatitis C antibody should be tested to screen for hepatitis C infection, according to the World Health Organization 4, 5
Autoimmune markers, such as antinuclear antibody, anti-smooth muscle antibody, and anti-mitochondrial antibody, should be considered to exclude autoimmune hepatitis and primary biliary cholangitis, as suggested by the American Association for the Study of Liver Diseases 4
Iron studies, including transferrin saturation and ferritin, should be performed to exclude hemochromatosis, according to the European Association for the Study of the Liver 4

The FIB-4 index calculation, using age, AST, ALT, and platelet count, should be used to estimate fibrosis stage, as recommended by the American Association for the Study of Liver Diseases 6, 5, 4
Clinical indicators suggesting cirrhosis, such as thrombocytopenia, AST > ALT ratio, hypoalbuminemia, elevated INR or prolonged prothrombin time, and elevated bilirubin, should prompt consideration of liver biopsy or advanced imaging, according to the American Gastroenterological Association 1, 2, 7, 5

Normal liver enzymes do not exclude cirrhosis, and advanced fibrosis may present with normal ALT and AST, making CBC and synthetic function tests essential, as recommended by the European Association for the Study of the Liver 4
Isolated GGT elevation is insufficient to diagnose liver injury, and should not be used as the sole marker, according to the American Association for the Study of Liver Diseases 7
ALT levels in NAFLD are typically between normal and 250 IU/L, usually <5× upper limit of normal, with ALT typically higher than AST until advanced disease, as suggested by the American Gastroenterological Association 7
Medication-induced steatosis should be excluded by reviewing for hepatotoxic medications, including corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, and valproic acid, as recommended by the American Association for the Study of Liver Diseases 1, 2