Evaluating abnormal liver chemistries: a clinical guideline
The ACG has released recommendations of preferred approaches for diagnosing and evaluating patients with abnormal liver test results.
The American College of Gastroenterology (ACG) has released a clinical practice guideline regarding the evaluation of abnormal liver chemistries.
The investigators reviewed evidence from the MEDLINE and EMBASE databases regarding the evaluation of abnormal liver chemistries, studies that examined the normal reference range for alanine aminotransferase (ALT), studies that examined the relationship between ALT and nonalcoholic fatty liver disease, and those that assessed the significance of elevated liver chemistries on overall mortality and morbidity. The authors of the guideline graded each of their recommendations as strong with a very low level of evidence.
A summary of the recommendations is as follows:
- Clinicians should repeat the lab panel or perform a clarifying test before the initiation of evaluation of abnormal liver chemistries.
- Testing for chronic hepatitis C virus (HCV) is conducted with anti-HCV, and confirmation is performed with HCV-RNA by nucleic acid testing. Acute HCV testing is with anti-HCV and HCV-RNA by nucleic acid.
- Testing for chronic hepatitis B is conducted with hepatitis B surface antigen testing, and acute hepatitis B is conducted with hepatitis B surface antigen and immunoglobulin M anti-hepatitis B core antigen.
- Patients presenting with acute hepatitis and possible fecal-oral exposure should be tested for acute hepatitis A. Testing for acute hepatitis E should also be considered for patients returning from endemic areas and whose tests for acute hepatitis A, B, and C are negative.
- Patients who have elevated BMI and other symptoms of metabolic syndrome, including diabetes, obesity, hyperlipidemia, and hypertension, should undergo screening for nonalcoholic fatty liver disease.
- Women who consume more than 140 g per week of alcohol, and men who consume more than 210 g, who present with aspartate aminotransferase (AST)>ALT may be at risk for alcoholic liver disease and should be counseled for alcohol cessation.
- Patients who have abnormal liver chemistries without acute hepatitis should undergo testing for hereditary hemochromatosis with an iron level, transferring saturation, and serum ferritin. Patients with transferrin saturation ≥45% or elevated serum ferritin should receive hereditary hemochromatosis gene mutation analysis.
- Patients with abnormal AST and ALT levels should undergo testing for autoimmune liver disease, particularly if they have another autoimmune condition.
- Patients with persistently elevated AST and ALT levels should undergo screening for Wilson's disease with serum ceruloplasmin testing, particularly if they are <55 years of age. In the setting of low ceruloplasmin, testing should be confirmed with 24-hour urinary copper and slit-lamp eye examination to identify pathognomonic Kayser-Fleischer rings.
- Patients with persistently elevated AST and ALT levels should undergo screening for alpha-1 anti-trypsin deficiency with alpha-1 anti-trypsin phenotype.
- Clinicians should ask patients who have abnormal liver chemistries about prescription and over-the-counter medications, nonprescribed complementary or alternative medicines, and dietary or herbal supplements that may be associated with drug-induced liver injury.
- Clinicians should consider a liver biopsy when serologic testing and imaging fails to determine a diagnosis, to stage a condition, or when multiple diagnoses are possible.
- Elevation of alkaline phosphatase should be confirmed with an elevation in gamma-glutamyl transferase (GGT). Clinicians should avoid using GGT as a screening test for underlying liver disease in the absence of other abnormal liver chemistries.
- Patients with elevated alkaline phosphatase with or without elevated bilirubin should undergo testing for primary biliary cholangitis with testing for anti-mitochondrial antibody.
- Patients with elevated alkaline phosphatase with or without elevated bilirubin should undergo testing for primary sclerosing cholangitis with magnetic resonance cholangiography or endoscopic retrograde cholangio-pancreatography in conjunction with IgG4.
- Among patients with ALT or AST levels <5 times the upper limit of normal, clinicians should use patient history and laboratory testing to assess for viral hepatitis B and C, alcoholic and nonalcoholic fatty liver disease, hemochromatosis, Wilson's disease, alpha-1-anti-trypsin deficiency, and autoimmune hepatitis and consider drugs or supplement-related injury.
- Among patients with ALT or AST levels that are 5 to 15 times the upper limit of normal, clinicians should also assess for acute hepatitis A, B, and C in addition to all etiologies for ALT/AST elevation <5 times the upper limit of normal.
- Among patients with ALT or AST levels >15 times the upper limit of normal or with massive elevated ALT >10,000 IU/I, clinicians should assess for acetaminophen toxicity and ischemic hepatopathy.
- Patients who present with acute hepatitis with an elevated prothrombin time or encephalopathy require immediate referral to a liver specialist.
- Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18-35. doi:10.1038/ajg.2016.517