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:

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The efficiency of blood donor screening programs could be improved by screening only blood donors who were born in LA or who have traveled in LA for extended periods, using a single enzyme immunoassay.

We used a panel of reagents, polyclonal and monoclonal antibodies, and lectins to define the expression of the ABH- and Lewis-related specificities on platelets and lymphocytes. We also determined the expression of the alpha 2- and alpha 3-L-fucosyltransferases necessary for their biosynthesis. The antigens that could be detected by immunofluorescence and Western blot analysis were based on type 2 monofucosylated structures. Antibodies directed toward types 1, 3, and 4 ABH-, X- and Lewis-related antigenic determinants were always negative because the small amounts of ABH and Lewis antigens adsorbed from the serum could not be detected by these techniques. The presence of the type 2 ABH antigens on intrinsic glycoproteins was controlled by the H gene. This correlates with the presence of alpha 2-L- fucosyltransferase and the absence of alpha 3-L-fucosyltransferase on platelets. In contrast, ABH antigens were not detected by immunofluorescence on normal peripheral lymphocytes. These cells thus have only the small amounts of antigens adsorbed from the serum, these being under control of the secretor and Lewis genes. This correlates with the absence of alpha 2-L-fucosyltransferase on lymphocytes. When lymphocytes were transformed in vitro by the Epstein-Barr virus (EBV), however, they strongly expressed the X and sialylated X antigens, which are specific markers of normal granulocytes and monocytes, respectively. Treatment of EBV-transformed lymphoblastoid cell lines with 12-O-tetradecanoylphorbol-13-O-acetate significantly decreased the expression of X and sialylated X antigens along with that of surface immunoglobulins, whereas it induced a significant expression of the H antigen under control of the H gene.