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Valenti L, Pelusi S, Bianco C, et al. Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update. Hepatol Commun. 2021;5(11):1824-1832doi: 10.1002/hep4.1794.
Valenti, L., Pelusi, S., Bianco, C., Ceriotti, F., Berzuini, A., Iogna Prat, L., Trotti, R., Malvestiti, F., D'Ambrosio, R., Lampertico, P., Colli, A., Colombo, M., Tsochatzis, E. A., Fraquelli, M., & Prati, D. (2021). Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update. Hepatology communications, 5(11), 1824-1832. https://doi.org/10.1002/hep4.1794
Valenti, Luca, et al. "Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update." Hepatology communications vol. 5,11 (2021): 1824-1832. doi: https://doi.org/10.1002/hep4.1794
Valenti L, Pelusi S, Bianco C, Ceriotti F, Berzuini A, Iogna Prat L, Trotti R, Malvestiti F, D'Ambrosio R, Lampertico P, Colli A, Colombo M, Tsochatzis EA, Fraquelli M, Prati D. Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update. Hepatol Commun. 2021 Nov;5(11):1824-1832. doi: 10.1002/hep4.1794. Epub 2021 Sep 14. PMID: 34520121; PMCID: PMC8557310.
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Hepatol Commun. 2021 Nov;5(11):1824-1832. doi: 10.1002/hep4.1794. Epub 2021 Sep 14.

Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update.

Hepatology communications

Luca Valenti, Serena Pelusi, Cristiana Bianco, Ferruccio Ceriotti, Alessandra Berzuini, Laura Iogna Prat, Roberta Trotti, Francesco Malvestiti, Roberta D'Ambrosio, Pietro Lampertico, Agostino Colli, Massimo Colombo, Emmanuel A Tsochatzis, Mirella Fraquelli, Daniele Prati

Affiliations

  1. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
  2. Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  3. Department of Medicine, Udine Hospital, Udine, Italy.
  4. Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, Italy.
  5. UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom.
  6. Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, Italy.
  7. CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
  8. Liver Center, IRCCS San Raffaele Hospital, Milan, Italy.
  9. Department of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, Italy.

PMID: 34520121 PMCID: PMC8557310 DOI: 10.1002/hep4.1794

Abstract

The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.

© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

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