Brief Communication: Clinical Implications of Short-Term Variability in Liver Function Test Results

4 March 2008 | Volume 148 Issue 5 | Pages 348-352

Background: Clinicians sometimes order liver tests as part of a screening examination or general work-up. Current guidelines do not recommend routine retesting of abnormal results in asymptomatic patients.

Objective: To characterize the magnitude of intraindividual variability of liver test results and determine the proportion of adults with persistently elevated levels after 1 positive test.

Design: Reliability study.

Setting: The NHANES (National Health and Nutrition Examination Survey) III First and Second Examinations (1988 to 1994).

Participants: 1864 men and women age 18 years or older living in the United States.

Measurements: Repeated measurements (mean, 17.5 days apart) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, -glutamyltransferase, and bilirubin.

Results: Using NHANES III cutoffs for normal levels, 38% of adults with initially elevated bilirubin levels had normal levels at the second examination. These proportions were 36%, 31%, 17%, and 12% for AST, ALT, alkaline phosphatase, and -glutamyltranferase, respectively. More than 95% of initially normal results remained normal. The results did not differ by alcohol consumption; hepatitis A, B, or C serologic status; recent infection; body mass index; or sociodemographic characteristics. Intraindividual variability was significantly higher for bilirubin (coefficient of variation, 23.4%) and ALT (coefficient of variation, 20.4%) than for AST (coefficient of variation, 13.9%), -glutamyltransferase (coefficient of variation, 13.8%), and alkaline phosphatase (coefficient of variation, 6.7%).

Limitations: Only 2 measurements were available. Complete liver disease history was lacking.

Conclusion: If retested, more than 30% of adults with elevated AST, ALT, or bilirubin levels would be reclassified as normal. Clinicians should be aware of the high intraindividual variability in common liver tests, and practice guidelines should explicitly recommend retesting of asymptomatic individuals with abnormal liver test results.

Editors' Notes Context Should clinicians work up or repeat liver tests when abnormal values are found in asymptomatic individuals? Contribution This analysis examined repeated liver tests (for aminotransferases, alkaline phosphatase, -glutamyltransferase, and bilirubin), obtained about 17 days apart, from 1864 men and women who participated in NHANES (National Health and Nutrition Examination Survey) III. More than 95% of the initially normal results remained normal, whereas 12% to 38% of the elevated values were normal at the second examination. Implication Intraindividual variability of liver tests is high: Many "abnormal" values in asymptomatic individuals are normal on retesting. —The Editors

 

Author and Article Information

From Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.

Grant Support: Dr. Selvin was supported by a National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (grant K01 DK076595).

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: The protocol for this study is not available. The statistical code is available to interested readers by contacting Dr. Lazo at mlazo{at}jhsph.edu. The data, which came from the NHANES III First and Second Examinations, are publicly available at http://www.cdc.gov/nchs/about/major/nhanes/nh3data.htm.

Requests for Single Reprints: Mariana Lazo, MD, ScM, Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205-2223; e-mail, mlazo{at}jhsph.edu.

Current Author Addresses: Drs. Lazo, Selvin, and Clark: Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205.

Author Contributions: Conception and design: M. Lazo, E. Selvin, J.M. Clark.

Analysis and interpretation of the data: M. Lazo, E. Selvin, J.M. Clark.

Drafting of the article: M. Lazo.

Critical revision of the article for important intellectual content: M. Lazo, E. Selvin, J.M. Clark.

Final approval of the article: M. Lazo, E. Selvin, J.M. Clark.

Statistical expertise: M. Lazo, E. Selvin.

Administrative, technical, or logistic support: J.M. Clark.

Collection and assembly of data: M. Lazo.

Read all Rapid Responses

Response

Pieter A Cohen

Annals Online, 4 Mar 2008 [Full text]

Effect of statins on transiently elevated aminotransferase levels

Weekitt Kittisupamongkol

Annals Online, 10 Mar 2008 [Full text]

Clinical Implications of Short-Term Variability in Liver Function Test Results

Gaurav Arora, et al.

Annals Online, 10 Mar 2008 [Full text]

Effect of inheritance on intraindividual variability in common liver tests

Liu Hong, et al.

Annals Online, 17 Mar 2008 [Full text]

Normalization and Normality

Agostino Colli, et al.

Annals Online, 31 Mar 2008 [Full text]

Prognostic evaluation of individuals with abnormal liver function tests

Hidekatsu Yanai

Annals Online, 3 Apr 2008 [Full text]

In Response

Mariana Lazo, et al.

Annals Online, 21 Apr 2008 [Full text]