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ARTICLE

Updated Definitions of Healthy Ranges for Serum Alanine Aminotransferase Levels

Daniele Prati, MD; Emanuela Taioli, MD, PhD; Alberto Zanella, MD; Emanuela Della Torre, DSc; Sonia Butelli, DSc; Emanuela Del Vecchio, DSc; Luciana Vianello, MD; Francesco Zanuso, MD; Fulvio Mozzi, DSc; Silvano Milani, PhD; Dario Conte, MD; Massimo Colombo, MD; and Girolamo Sirchia, MD, FRCPath (Edin)

2 July 2002 | Volume 137 Issue 1 | Pages 1-10

Background: Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. Current standards for "normal" ALT level were defined by using populations that included persons with subclinical liver disease.

Objective: To update definitions of healthy ranges for serum ALT level.

Design: Retrospective cohort study.

Setting: A university hospital in Milan, Italy.

Participants: 6835 persons who were first-time blood donors from 1995 through 1999, were negative for anti–hepatitis C virus (HCV), and had no contraindications to donation and 209 persons who attempted to donate blood from 1990 through 1999 but were found to have anti–HCV antibodies. Of the latter group, 131 had HCV viremia.

Measurements: Univariate and multivariate analyses examined associations between clinical and laboratory factors and ALT levels. Healthy ranges for ALT were computed from the population at lowest risk for liver disease. Sensitivity and specificity of healthy ALT ranges were evaluated in the donors with HCV antibodies, of whom 133 had liver biopsy.

Results: Serum ALT activity was independently related to body mass index and to laboratory indicators of abnormal lipid or carbohydrate metabolism. Updated upper limits (for men, 500 nkat/L [30 U/L]; for women, 317 nkat/L [19 U/L]) were lower than current limits (for men, 667 nkat/L [40 U/L]; for women, 500 nkat/L [30 U/L]) and, during 6-month follow-up, showed superior sensitivity in identifying participants with HCV viremia (sensitivity, 76.3% [95 % CI, 69.1% to 83.6%] vs. 55% [CI, 46.4% to 63.5%]). The related tradeoff in specificity was acceptable (88.5% [CI, 79.2% to 94.6%] vs. 97.4% [91% to 99.7%]). The increased sensitivity targeted patients with minimal to mild histologic lesions.

Conclusion: In patients with chronic HCV infection or nonalcoholic fatty liver disease, revision of normal limits for ALT level is advisable.

Editors' Notes Context Current upper limits (500 nkat/L [30 U/L] for women, 667 nkat/L [40 U/L] for men) for serum alanine aminotransferase (ALT) level were defined in populations that included persons with nonalcoholic fatty liver disease (NAFLD) and persons with hepatitis C virus (HCV) infection. Contribution This study redefined ALT limits in blood donors at low risk for NAFLD and without hepatitis B or C (317 nkat/L [19 U/L] in women, 500 nkat/L [30 U/L] in men). When applied to 209 anti-HCV-positive donors, the new thresholds had 76.3% sensitivity and 88.5% specificity in identifying patients with hepatitis C viremia compared with 55% and 97.4% for old thresholds. Implications Laboratories should consider revising the upper limits of normal for ALT to improve the sensitivity of this test in identifying subclinical liver disease. –The Editors

 

Author and Article Information

From Centro Transfusionale e di Immunologia dei Trapianti, Laboratorio di Epidemiologia, Divisione di Ematologia, Istituto di Statistica Medica e Biometria, Cattedra di Gastroenterologia, and Istituto di Medicina Interna, IRCCS Ospedale Maggiore and Università degli Studi di Milano, Milan, Italy.

Grant Support: By a grant from IRCCS Ospedale Maggiore Policlinico, Milan, Italy (51501—Ricerca Corrente 1998).

Requests for Single Reprints: Daniele Prati, MD, Centro Trasfusionale e di Immunologia dei Trapianti IRCCS Ospedale Maggiore Via Francesco Sforza, 35 20122 Milano, Italy; e-mail, dprati{at}yahoo.com.

Current Author Addresses: Drs. Prati, Della Torre, Butelli, Del Vecchio, Vianello, Zanuso, Mozzi, and Sirchia: Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore di Milano, via F.Sforza, 35, 20122 Milano, Italy.

Dr. Taioli: Laboratorio di Epidemiologia, IRCCS Ospedale Maggiore di Milano, via F.Sforza, 28, 20122 Milano, Italy.

Dr. Zanella: Divisione di Ematologia, IRCCS Ospedale Maggiore di Milano, Via F.Sforza, 35, 20122 Milano, Italy.

Dr. Milani: Istituto di Statistica Medica e Biometria, Università degli Studi, Via Venezian 1, 20133 Milano, Italy.

Dr. Conte: Cattedra di Gastroenterologia, Università degli Studi and IRCCS Ospedale Maggiore di Milano, via F.Sforza, 35, 20122 Milano, Italy.

Dr. Colombo: Istituto di Medicina Interna, Università degli Studi and IRCCS Ospedale Maggiore di Milano, via F.Sforza, 35, 20122 Milano, Italy.

Author Contributions: Conception and design: D. Prati, E. Taioli, A. Zanella.

Analysis and interpretation of the data: D. Prati, E. Taioli, L. Vianello, F. Mozzi, S. Milani, D. Conte, M. Colombo.

Drafting of the article: D. Prati, E. Taioli, A. Zanella, D. Conte.

Critical revision of the article for important intellectual content: D. Prati, E. Taioli, A. Zanella, F. Mozzi, S. Milani, D. Conte, M. Colombo, G. Sirchia.

Final approval of the article: D. Prati, E. Taioli, A. Zanella, E. Della Torre, S. Butelli, E. Del Vecchio, L. Vianello, F. Zanuso, F. Mozzi, S. Milani, D. Conte, M. Colombo, G. Sirchia.

Provision of study materials or patients: D. Prati, E. Della Torre, S. Butelli, E. Del Vecchio, L. Vianello, F. Zanuso, F. Mozzi, D. Conte, M. Colombo, G. Sirchia.

Statistical expertise: E. Taioli, S. Milani.

Obtaining of funding: D. Prati.

Administrative, technical, or logistic support: E. Della Torre, S. Butelli, E. Del Vecchio, F. Zanuso.

Collection and assembly of data: E. Della Torre, S. Butelli, E. Del Vecchio, L. Vianello, F. Zanuso, F. Mozzi.

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