Evaluation of Abnormal Liver Chemistries

Publication Date: January 1, 2017
Last Updated: March 14, 2022


1. Before initiation of evaluation of abnormal liver chemistries, one should repeat the lab panel and/or perform a clarifying test (e.g., GGT if serum alkaline phosphate is elevated) to confirm that the liver chemistry is actually abnormal. (Strong  “We recommend”, Very low)

2. Testing for chronic hepatitis C is conducted with anti-HCV and confirmation is performed with HCV-RNA by nucleic acid testing. Risk factors for hepatitis C include history of intranasal or intravenous drug use, tattoos, body piercings, blood transfusions, high risk sexual conduct, and those born between 1945 and 1965. Testing for acute hepatitis C is with anti-HCV and HCV RNA by nucleic acid testing. (Strong  “We recommend”, Very low)

3. Testing for chronic hepatitis B is conducted with HBsAg testing. Testing for acute hepatitis B is with HBsAg and IgM anti-HBc. The following groups are at highest risk: persons born in endemic or hyperendemic areas (HBsAg prevalence >2%), men who have sex with men, persons who have ever used injection drugs, dialysis patients, HIV-infected individuals, pregnant women, and family members, household members, and sexual contacts of HBV-infected persons. (Strong  “We recommend”, Very low)

4. Testing for acute Hepatitis A (IgM HAV) should occur in patients presenting with acute hepatitis and possible fecal-oral exposure. Testing for acute hepatitis E (IgM HEV) should also be considered in those returning from endemic areas and whose tests for acute hepatitis A, B, and C are negative. (Strong  “We recommend”, Very low)

5. Patients with elevated BMI and other features of metabolic syndrome including diabetes mellitus, overweight or obesity, hyperlipidemia, or hypertension with mild elevations of ALT should undergo screening for NAFLD with ultrasound. (Strong  “We recommend”, Very low)

6. Women consuming more than 140 g per week or men consuming more than 210 g per week who present with AST>ALT should be considered at risk for alcoholic liver disease and should be counseled for alcohol cessation. (Strong  “We recommend”, Very low)

7. All patients with abnormal liver chemistries in the absence of acute hepatitis should undergo testing for hereditary hemochromatosis with an iron level, transferrin saturation, and serum ferritin. HFE gene mutation analysis should be performed in patients with transferrin saturation ≥45% and/or elevated serum ferritin. (Strong  “We recommend”, Very low)

8. Patients with abnormal AST and ALT levels, particularly patients with other autoimmune conditions, should undergo testing for autoimmune liver disease including ANA, ASMA, and globulin level. (Strong  “We recommend”, Very low)

9. Patients with persistently elevated AST and ALT levels, especially patients <55 years of age, should undergo screening for Wilson’s disease with serum ceruloplasmin testing. In the setting of low ceruloplasmin, confirmatory testing with 24-h urinary copper and slit-lamp eye examination to identify pathognomonic Kayser–Fleischer rings should occur. (Strong  “We recommend”, Very low)

10. Patients with persistently elevated AST or ALT should undergo screening for alpha-1 anti-trypsin (A1AT) defi ciency with alpha-1 anti-trypsin phenotype. (Strong  “We recommend”, Very low)

11. Physicians should ask patients with abnormal liver chemistries about prescribed and over-the-counter medications, non-prescribed complementary or alternative medicines, and dietary or herbal supplements which may be associated with drug-induced liver injury (DILI). (Strong  “We recommend”, Very low)

12. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible. (Strong  “We recommend”, Very low)

13. An elevation of alkaline phosphatase should be confi rmed with an elevation in GGT. Given its lack of specifi city for liver disease, GGT should not be used as a screening test for underlying liver disease in the absence of other abnormal liver chemistries. (Strong  “We recommend”, Very low)

14. Patients with alkaline phosphatase elevation with or without elevation of bilirubin should undergo testing for PBC (formerly named primary biliary cirrhosis) with testing for anti-mitochondrial antibody. (Strong  “We recommend”, Very low)

15. Patients with alkaline phosphatase elevation with or without elevation of bilirubin should undergo testing for PSC with MR cholangiography or ERCP in conjunction with IgG4. (Strong  “We recommend”, Very low)

16. In those with ALT and/or AST levels <5X ULN, the history and laboratory testing should assess for viral hepatitis B and C, alcoholic and NAFLD, hemochromatosis, Wilson’s disease, alpha-1-anti-trypsin defi ciency, autoimmune hepatitis and consider drugs/supplement related injury. (Strong  “We recommend”, Very low)

17. In those with ALT and/or AST levels 5–15X ULN, evaluation should also assess for acute hepatitis A, B, and C in addition to all etiologies for AST/ALT elevation less than 5x ULN. (Strong  “We recommend”, Very low)

18. In those with ALT and/or AST levels >15X ULN, or massive elevation ALT of >10,000 IU/l, evaluation should also assess for acetaminophen toxicity and ischemic hepatopathy (shock liver). (Strong  “We recommend”, Very low)

19. A patient presenting with acute hepatitis with an elevated prothrombin time, and/or encephalopathy requires immediate referral to liver specialist. (Strong  “We recommend”, Very low)

Recommendation Grading




Evaluation of Abnormal Liver Chemistries

Authoring Organization

Publication Month/Year

January 1, 2017

Last Updated Month/Year

June 2, 2023

Supplemental Implementation Tools

Document Type


External Publication Status


Country of Publication


Document Objectives

These recommendations are intended for use by physicians and health care providers and suggest preferred approaches to the diagnoses and evaluation of those with abnormal liver tests

Target Patient Population

Patients with abnormal liver function tests

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Home health, Hospital, Long term care, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D008107 - Liver Diseases, D008099 - Liver, D000410 - Alanine Transaminase, D001219 - Aspartate Aminotransferases, D008111 - Liver Function Tests


liver function, liver chemistry, alanine transaminase

Source Citation

Kwo, Paul Y MD, FACG, FAASLD; Cohen, Stanley M MD, FACG, FAASLD; Lim, Joseph K MD, FACG, FAASLD. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries, American Journal of Gastroenterology: January 2017 - Volume 112 - Issue 1 - p 18-35 doi: 10.1038/ajg.2016.517

Supplemental Methodology Resources

Data Supplement