Mildly Elevated Liver Transaminase Levels: Causes and Evaluation

 

Am Fam Physician. 2017 Dec 1;96(11):709-715.

  Patient information: See related handout on elevated liver enzymes, written by the authors of this article.

Author disclosure: No relevant financial affiliations.

Mild, asymptomatic elevations (less than five times the upper limit of normal) of alanine transaminase and aspartate transaminase levels are common in primary care. It is estimated that approximately 10% of the U.S. population has elevated transaminase levels. An approach based on the prevalence of diseases that cause asymptomatic transaminase elevations can help clinicians efficiently identify common and serious liver disease. The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease. Uncommon causes include drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis. Rare causes include alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic sources, such as thyroid disorders, celiac sprue, hemolysis, and muscle disorders, are also associated with mildly elevated transaminase levels. The initial evaluation should include an assessment for metabolic syndrome and insulin resistance (i.e., waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level); a complete blood count with platelets; measurement of serum albumin, iron, total iron-binding capacity, and ferritin; and hepatitis C antibody and hepatitis B surface antigen testing. The nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/nonalcoholic fatty liver disease index can be helpful in the evaluation of mildly elevated transaminase levels. If testing for common causes is consistent with nonalcoholic fatty liver disease and is otherwise unremarkable, a trial of lifestyle modification is appropriate. If the elevation persists, hepatic ultrasonography and further testing for uncommon causes should be considered.

Mild, asymptomatic elevations of alanine transaminase (ALT) and aspartate transaminase (AST) levels, defined as less than five times the upper limit of normal, are common in primary care. The prevalence of elevated transaminase levels is estimated to be approximately 10%, although less than 5% of these patients have a serious liver disease.1,2 Understanding the epidemiology of each condition that causes asymptomatic elevated transaminase levels can guide the evaluation.36 Elevations greater than five times the upper limit of normal should prompt immediate evaluation6 but are beyond the scope of this article.

WHAT IS NEW ON THIS TOPIC: MILDLY ELEVATED LIVER TRANSAMINASE LEVELS

The NAFLD fibrosis score is a calculator that uses clinical data to predict risk of liver-related complications and death from advanced disease. Clinicians should refer patients with a high NAFLD fibrosis score, increased risk of progression, or coexisting chronic liver disease to a gastroenterologist.

In a two-year prospective study in the United Kingdom that included nearly 1,300 primary care patients with abnormal transaminase levels, excluding fatty liver disease (38% of patients), less than 5% of diagnostic workups revealed significant liver disease, and only 17 persons (1.3%) had serious liver disease that required immediate treatment.

NAFLD = nonalcoholic fatty liver disease.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Consider gastroenterology referral for patients with persistent elevations of transaminase levels and for those who are at risk of nonalcoholic fatty liver disease progression.

C

10

Repeat liver enzyme testing is not necessary in the initial workup for elevated transaminase levels.

B

43

Lifestyle modifications with follow-up are appropriate if history, physical examination, and workup suggest nonalcoholic fatty liver disease.

B

46, 10, 11, 43

If the history and physical examination are unrevealing, clinicians should initiate a stepwise epidemiologic approach to diagnosing the cause of elevated transaminase levels.

C

35


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Consider gastroenterology referral for patients with persistent elevations of transaminase levels and for those who are at risk of nonalcoholic fatty liver disease progression.

C

10

Repeat liver enzyme testing is not necessary in the initial workup for elevated transaminase levels.

B

43

Lifestyle modifications with follow-up are appropriate if history, physical examination, and workup suggest nonalcoholic fatty liver disease.

B

46, 10, 11, 43

If the history and physical examination are unrevealing, clinicians should initiate a stepwise epidemiologic approach to diagnosing the cause of elevated transaminase levels.

C

35


A = consistent, good-quality patient-oriented

The Authors

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ROBERT C. OH, MD, MPH, is chief medical officer at Martin Army Community Hospital, Fort Benning, Ga., and an associate professor of family medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md....

THOMAS R. HUSTEAD, MD, is family medicine physician at Hardin Memorial Health, Elizabethtown, Ky. At the time this article was written, he was a commander at Supreme Headquarters Allied Powers Europe Healthcare Facility, Mons, Belgium.

SYED M. ALI, MD, is a third-year resident in the Department of Family Medicine at Fort Belvoir (Va.) Community Hospital.

MATTHEW W. PANTSARI, MD, is a partner at Gastroenterology Consultants of Augusta (Ga.).

Address correspondence to Robert C. Oh, MD, MPH, Martin Army Community Hospital, 6600 Van Aalst Blvd., Fort Benning, GA 31905 (e-mail: roboh98@gmail.com). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

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