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.

Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update / L. Valenti, S. Pelusi, C. Bianco, F. Ceriotti, A. Berzuini, L. Iogna Prat, R. Trotti, F. Malvestiti, R. D'Ambrosio, P. Lampertico, A. Colli, M. Colombo, E.A. Tsochatzis, M. Fraquelli, D. Prati. - In: HEPATOLOGY COMMUNICATIONS. - ISSN 2471-254X. - 5:11(2021 Nov), pp. 1824-1832. [10.1002/hep4.1794]

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

L. Valenti
Primo
;
S. Pelusi
Secondo
;
F. Malvestiti;P. Lampertico;
2021

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.
English
Adolescent; Adult; Age Factors; Aged; Alanine Transaminase; Blood Donors; Body Mass Index; Cross-Sectional Studies; Female; Healthy Volunteers; Humans; Liver Diseases; Male; Middle Aged; Odds Ratio; ROC Curve; Reference Values; Sex Factors; Young Adult;
Settore MED/09 - Medicina Interna
Articolo
Esperti anonimi
Pubblicazione scientifica
   Liver Investigation: Testing Marker Utility in Steatohepatitis
   LITMUS
   EUROPEAN COMMISSION
   777377
nov-2021
14-set-2021
Wiley Blackwell Publishing
5
11
1824
1832
9
Pubblicato
Periodico con rilevanza internazionale
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.1794
scopus
pubmed
crossref
wos
Aderisco
info:eu-repo/semantics/article
Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update / L. Valenti, S. Pelusi, C. Bianco, F. Ceriotti, A. Berzuini, L. Iogna Prat, R. Trotti, F. Malvestiti, R. D'Ambrosio, P. Lampertico, A. Colli, M. Colombo, E.A. Tsochatzis, M. Fraquelli, D. Prati. - In: HEPATOLOGY COMMUNICATIONS. - ISSN 2471-254X. - 5:11(2021 Nov), pp. 1824-1832. [10.1002/hep4.1794]
open
Prodotti della ricerca::01 - Articolo su periodico
15
262
Article (author)
no
L. Valenti, S. Pelusi, C. Bianco, F. Ceriotti, A. Berzuini, L. Iogna Prat, R. Trotti, F. Malvestiti, R. D'Ambrosio, P. Lampertico, A. Colli, M. Colomb...espandi
File in questo prodotto:
File Dimensione Formato  
Hepatology Communications - 2021 - Valenti - Definition of Healthy Ranges for Alanine Aminotransferase Levels A 2021.pdf

accesso aperto

Descrizione: articolo completo
Tipologia: Publisher's version/PDF
Dimensione 141.58 kB
Formato Adobe PDF
141.58 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/909619
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 49
  • ???jsp.display-item.citation.isi??? 41
social impact