Factors associated with serum alanine transaminase activity in healthy subjects: Consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C

Abstract

In clinical research, the definition of the upper limit of normal (ULN) alanine transaminase (ALT) is never detailed. However, such a definition can vary and may have practical consequences. Our aim was to assess factors associated with serum ALT activity in apparently healthy subjects and then to apply seven different definitions of ULN in three different populations so as to assess the prevalence of subjects with normal ALT among blood donors and among hepatitis C patients before (normal ALT hepatitis C patients) and after treatment ( Measuring serum alanine transaminase (ALT) activity is a very common screening test as part of a routine evaluation of patients. The definition of normal and abnormal serum ALT activity has pragmatic consequences in at least three circumstances. The first involves the selection of donors so as to prevent the transmission of non-A, non-E viruses. The second is the identification, among patients with chronic hepatitis C, of a subgroup of patients with chronic hepatitis C and normal ALT who could represent a specific group in terms of liver fibrosis progression 1 or efficacy of interferon (IFN) treatment. 2 The third concerns the definition of a response after treatment of hepatitis C in which serum ALT measurements are very often used to define responders. 3 In these three circumstances, a change in the definition of the normal value or in the prevalence of factors associated with ALT serum activity could cause practical changes. For example, a decrease in the upper limit of normal (ULN) value reduces the number of donors in a blood bank, decreases the prevalence of patients with chronic hepatitis C and normal ALT, and decreases the number of IFN responders in a randomized trial.To better understand the definition of normal and abnormal ALT, we assessed, in a prospective cohort of 1,033 blood donors, the distribution and factors associated with abnormal ALT. From these results, a new definition of the ULN ALT was suggested. Then, to observe clinical implications, we applied seven different definitions of an upper normal limit to three populations of subjects with normal ALT: blood donors, hepatitis C patients before treatment (normal ALT hepatitis C patients), and after treatment (IFN responders). All ALT measurements were performed using the same technique. PATIENTS AND METHODSBlood Donors. A total of 1,085 donors were consecutively investigated in the Blood Center of Hô pital Broussais in Paris, France. From this population, 52 donors were excluded because of presence Abbreviations: ALT, alanine transaminase; IFN, interferon; ULN, upper limit of normal; GGT, ␥-glutamyl transpeptidase; BMI, body mass index.*The MULTIVIRC group (Groupe Hospitalier Pitié-Salpêtrière): Service d'Hépato-Gastroentérologie:

Spectrum of NAFLD and Diagnostic Implications of the Proposed New Normal Range for Serum ALT in Obese Women *

“…Additionally, both the negative and positive predictive values for NASH are poor. We also analyzed the diagnostic utility of ALT applying the upper level of 44 U/L in subjects with a BMI Ͼ23 kg/m 2 (which is obviously all of our cohort), as suggested by Piton et al 23 For NASH, the sensitivity was 18%, specificity 96%, and negative and positive predictive values were 71% and 70%, respectively. Taken together, irrespective of the multiple ALT standards suggested to date, no cutoff value is diagnostically useful to detect the presence of NASH.…”

Should chronic HBV infected patients with normal ALT treated: debate

“…The extent of liver cell necrosis and degree of elevated ALT level do not always correlate, and ALT measurements may fail to identify patients with necro-inflammatory activity or fibrosis, as seen in hepatitis C [12,13]. In addition, the ALT activity may vary with body mass index, sex, abnormal lipid and carbohydrate metabolism as well as the time of the day [14,15].…”

Anti-HBc Screening of Blood Donors in Bangladesh: Relevance to Containment of HBV Propagation

“…ALT more than 30 IU/L is regarded as elevated level of ALT by some investigators. 17,18 It may be possible to discard donor blood with elevated ALT and anti-HBc positivity. Next, NAT screening may be accomplished as a pilot project in some establishment and after analysis of pros and cons, expanded usage of NAT may be considered.…”