Limiting the Testing of Aspartate Aminotransferase: Using the Proper Upper Limit of the Reference Interval of Alanine AminotransferaseThe Authors’ Reply

Xu et al 1 published an article entitled “Limiting the Testing of AST: A Diagnostically Nonspecific Enzyme,” in which the authors claimed that only aspartate aminotransferase (AST) could be measured when alanine aminotransferase (ALT) exceeds a predetermined limit, and so a substantial health care budget could be saved. That is a great idea. However, some questions need to be clarified about this article. According to the description in the Materials and Methods section, the objects tested were in the city of Edmonton, which is the capital of Alberta, Canada. However, the upper limit of the reference interval (ULRI) of ALT 1,2 (30 U/L) used in the article came from Italy. Our questions are as follows: (1) is the ULRI used in this article suitable to evaluate the objects? and (2) why did the authors not use the reference intervals of ALT 3 that have been generated from the local area? In addition, we found that only the reference intervals of AST were cited in the article but not that of ALT. Actually, the ULRI of ALT has been shown to be higher than the ULRI of AST in many studies. 4-7 For example, in Canada, 5 the ULRI of ALT is 40 U/L, while the ULRI of AST is 30 U/L for both males and females. In China, 6 the ULRIs of ALT are 50 U/L (males) and 40 U/L (females), while the ULRIs of AST are 40 U/L (males) and 35 U/L (females), respectively. In Tanzania, 6 the ULRIs of ALT are 55 U/L (males) and 45 U/L (females), while the ULRIs of AST are 53 U/L (males) and 35 U/L (females). In Canada recently, 7 the ULRIs of ALT are 78 U/L or 62 U/L (males) and 41 U/L or 44 U/L (females), while the ULRIs of AST are 54 U/L or 39 U/L and 34 U/L or 39 U/L. Thus, to us, the ULRI of ALT used in Xu et al 1 is not appropriate in the study. In our opinion, the authors should choose the upper limit of ALT in their own region and use the proper upper limit of ALT for initiating AST testing. It would be better if the authors chose the 80th percentile level of ALT or the level of medical decision levels. 8 To a certain extent, it may reduce the chance of missing a high value of AST. As we all know, people would prefer to spend more money to avoid a misdiagnosis. We read with interest the letter by Zhang and Guo concerning our article on aspartate aminotransferase (AST)/alanine aminotransferase (ALT). 1 We write this letter with the belief that laboratory results should be readily interpretable as well as actionable. However, some comments should be made about their response. Zhang and Guo reference an article by Perkins et al 2 and state that reference intervals by Perkins et al can be applied to the AST and ALT of Canadian subjects. Sadly, those reference ranges originated from the measurement of umbilical cord blood samples and are not relevant to our work, which was performed on regular serum/plasma samples. Canada is a large country (9.985 million km 2 ) spanning six time zones, with broad ethnic diversity and with clinical laboratories using a variety of chemistry analyzers. These factors make Canadian harmonized reference intervals difficult to implement. AST and ALT testing for the Canadian Health Measures Survey (CHMS) 3 was performed on a Vitros 5600 FS (Ortho Clinical Diagnostics, Raritan, NJ). Transference studies have been undertaken with the earlier CALIPER [Canadian Laboratory Initiative on Paediatric Reference Intervals] study on pediatric populations. 4 Transference and validation 5 have not been completed for the CHMS study. To say, as Zhang and Guo imply, that if a laboratory in a country publishes a reference range, then it is applicable to a whole country is not correct, and we reject their contention that we chose an inappropriate upper limit of reference interval for our study because of other published reference ranges for Canadian populations. However, there are programs under way in some countries 6,7 to develop countrywide harmonized reference ranges, but these are just beginning in Canada. From a clinical perspective, AST results are very difficult to interpret since AST is derived from multiple tissues, and common coexisting ailments can cause puzzling increases. ALT, a far more specific enzyme, is highly correlated to AST and in most situations provides superior diagnostic information compared with AST. If we had our druthers, AST would be deleted from test formularies universally as others have proposed. 8 Since it is difficult to convince clinicians to completely stop AST testing, we have proposed that low ALT values be a surrogate for AST. For high ALT values, the laboratory would report the diagnostically nonhelpful AST.

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