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PAPERS: Hyeon Chang Kim, Chung Mo Nam, Sun Ha Jee, Kwang Hyub Han, Dae Kyu Oh, and Il Suh Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study BMJ 2004; 328: 983 [Abstract] [Full text]

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lowering transaminase limits-a burden or a boon

shyam s menon   (27 April 2004)

‘Normal’ serum aminotransferase concentrations?

Patrick J Twomey, Adie Viljoen   (14 May 2004)

lowering transaminase limits-a burden or a boon 27 April 2004
shyam s menon, specialist registrar, gastroenterology russells hall hospital, dudley Send response to journal: Re: lowering transaminase limits-a burden or a boon	kim et al have raised important issues regarding cutoff values of transaminases.1 what is not clear is if data such as alcohol consumption were updated continuously as changing consumption patterns would skew the net result resulting in bias. transaminase data would seem to be intial data on entry into the study which would be difficult to correlate with mortality at the end of the study from liver diseases. it would have indeed been useful to have identified actual liver pathology which could have provided more meaning to observed differences in transaminase levels. this study is relevent in the context of the emerging epidemic of non alcoholic steato hepatitis(NASH) as lowering the upper limit of transaminase levels might translate into a large increase in the absolute numbers of patients who would require evaluation for an uncertain clinical benefit owing to the detection of mild abnormalities.2 references 1.Hyeon Chang Kim, Chung Mo Nam, Sun Ha Jee, Kwang Hyub Han, Dae Kyu Oh, and Il Suh Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study BMJ 2004; 328: 983-0. 2.Kaplan, MM. Alanine aminotransferase levels: What's normal? (editorial). Ann Intern Med 2002; 137:50. Competing interests: None declared
‘Normal’ serum aminotransferase concentrations? 14 May 2004
Patrick J Twomey, Consultant Chemical Pathology The Ipswich Hospital, Department of Chemical Pathology, Heath Road, Ipswich, IP4 5PD, Adie Viljoen Send response to journal: Re: ‘Normal’ serum aminotransferase concentrations?	Editor – Kim and co-workers (1) have investigated and suggested reference limits for aminotransferase concentrations and mortality from liver disease. However, for health derived reference limits to be used there must be a high degree of analytical and population group transferability (2). It would therefore be essential to report on the analytical methods employed when commenting on specific results as per the STARD (Standards for Reporting of Diagnostic Accuracy) initiative which was co-published by this journal (3). Due to the lack of assay standardization (2, 4) and therefore non-comparability, comparing absolute values (e.g. 40 IU/L) may be misleading and confusing. For example, three different ALT assays harmonised to the International Federation of Clinical Chemistry method and routinely employed by accredited laboratories have significantly different reference intervals: 21–72 IU/L for the Vitros 250® (Ortho Diagnostics, www.orthoclinical.com), <45 IU/L for the AU640® (Olympus Diagnostics, www.olympusamerica.com/dsg_section/dsg_chemistrysys.asp) and 30–65 IU/L for the Dimension RxL® (Dade Behring). Furthermore reference intervals differ for the two different enzymes AST and ALT (2) and therefore use of a common single upper reference limit (1) is discouraged. The biological variation for ALT is approximately 25%. Taking the ALT concentration at the suggested (1) upper reference limit of 40 IU/L, the 95% confidence interval of a single estimate would be 20–60 IU/L. This would render the utilisation of a population cut-off for ALT as impractical for routine clinical practice when investigating individuals with single serum estimations. It would also be important to report on, and control for, other factors such as body mass index (lower range in the Far East), viral hepatitis (higher incidence in the Far East), age, gender, recent exercise, muscle injury and haemolysis as such issues may significantly influence aminotransferase values (4). It needs to be emphasized that if the upper normal limit is taken at 40 IU/L, 97.5% of values would be equal to or below this, but this would only be equal to two SD above the mean if the distribution was Gaussian. The distribution of aminotransferases show positive skewness and would require transformation before one can state that the upper normal limit is two SD above the mean level (5). References: 1. Kim HC, Nam CM, Jee SH, Han KH, Oh DY, Suh I. Normal serum aminotransferase concentration and risk of mortality from liver disease: prospective cohort study. BMJ 2004; 328:983-86 2. Burtis CA, Ashwood ER. Tietz textbook of clinical chemistry. 3rd edition. WB Saunders: Philadelphia; 1999. 3. Patrick M. Bossuyt, Johannes B. Reitsma, David E. Bruns, Constantine A. Gatsonis, Paul P. Glasziou, Les M. Irwig, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003; 326:41-44. 4. National Academy of Clinical Biochemistry. D. Robert Dufour, John A. Lott, Frederick S. Nolte, David R. Gretch, Raymond S. Koff, and Leonard B. Seeff Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests. Clin. Chem. 2000; 46:2027-2049. 5. Roderick P. Commentary: Liver function tests: defining what’s normal. BMJ 2004; 328:987. Competing interests: None declared