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; Girolamo Sirchia, MD, FRCPath (Edin)
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, email@example.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.
Prati D, Taioli E, Zanella A, Torre ED, Butelli S, Del Vecchio E, et al. Updated Definitions of Healthy Ranges for Serum Alanine Aminotransferase Levels. Ann Intern Med. 2002;137:1-10. doi: 10.7326/0003-4819-137-1-200207020-00006
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Published: Ann Intern Med. 2002;137(1):1-10.
Serum alanine aminotransferase (ALT) concentration is the most commonly used variable for assessment of liver disease (1, 2). However, particularly in the case of chronic hepatitis C virus (HCV) infection, ALT measurement often fails to identify patients with minimal to mild necroinflammatory activity (3-7).
Current upper limits of normal for ALT level were set, on average, at 667 nkat/L (40 U/L) (range, 500 to 833 nkat/L [30 to 50 U/L]) in studies conducted over the past 10 years (1, 3-5, 7, 8). Such thresholds, however, were mostly computed in the 1980s, when ALT testing was introduced as a surrogate marker for the screening of non-A, non-B hepatitis among blood donors and before anti-HCV testing and restrictive behavioral criteria for donor selection were implemented. Furthermore, so-called “reference” populations were likely to include many persons with nonalcoholic fatty liver disease, now recognized as the most prevalent cause of chronic liver disease in developed countries (8-10). Current reference ranges for ALT level probably underestimate the frequency of chronic liver disease. Because dietary and behavioral risks for liver disease are widespread in many countries, a critical revision of ALT limits would require the definition of “healthy ranges” rather than a generic update of “normal ranges.” Thus far, several factors have hampered this task. For example, to obtain solid data, many clinical, biochemical, and behavioral variables potentially related to liver disease must be investigated, requiring screening of large numbers of persons. Furthermore, repeated blood donors, who currently represent the vast majority of blood-donation candidates, cannot be included in the sampling frame, because they have been selected on the basis of ALT activity during the past two decades.
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Gastroenterology/Hepatology, Infectious Disease, Liver Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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