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AASLD-FDA-NIH-PhRMA*- Hepatotoxicity Special Interest Group Meeting
2008 Presentations
Clinical meaning of elevated serum aminotransferase activity [PDF] 
Naga Chalasani, MD,
Indiana University School of Medicine
Abstract
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are widely distributed in cell throughout the body.1,2 AST is found primarily in heart, liver, skeletal muscle and kidney while ALT is found primarily in liver and kidney, with lesser amounts in heart and skeletal muscle. AST and ALT activity in liver are about 7,000 and 3,000 times serum activities, respectively. ALT is exclusively cytoplasmic whereas all cells have mitochondrial and cytoplasmic forms of AST. Elevated serum AST may be seen not only in liver disease but in a variety of other conditions such as muscle injury, hemolysis, kidney injury whereas elevated serum ALT is more specifically indicative of liver disease. Besides liver injury, a large number of physiological and non-physiological factors affect AST and ALT activity.3,4 These include diurnal variation, day to day variability, race and gender, and exercise. Specimen storage may affect serum AST and ALT activity. AST is stable at room temperature for 3 days, in refrigerator for 2 weeks and stable for years in a frozen state whereas ALT is stable at room temperature for 3 days, in refrigerator for 2 weeks but there is marked decrease in ALT activity in freezing/thawing. As technology has evolved there is less variability in AST and ALT measurements between laboratories but each laboratory has its own reference range. Surprisingly there is no standardized reference range for these tests that is accepted universally and there is striking variability how different laboratories establish their reference range for the ALT. 5
In this presentation, the speaker will discuss the
- Properties of AST and ALT (location, half-life, etc)
- Clinical value of different patterns of elevated serum AST and ALT values
- Clinical value of different levels of abnormal AST and ALT values in serum
- Inconsistency among different laboratories in the reference range
- Discussion of ALT as a population screening test
References:
- Karmen A, Wrobleswski F, Ladue JS. Transaminase activity in human blood. J Clin Invest 1955; 34:126-31. [PMID: 13221663]
- Karmen A. A note on the spectrometric assay of glutamic-oxalacetic transaminases in human blood serum. J Clin Invest 1955;34:131-3. [PMID 13221664]
- Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000;46:2027-49. [PMID 11106349]
- Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem 2000;46:2050-68. [PMID 11106350]
- Dutta A, Chalasani N. Variability in the Upper Limit of ALT among different clinical laboratories in Indiana: A state-wide survey. Poster presentation, DDW 2008 (See attached, to appear in Gastroenterology 2008, May supplement issue)
Biography
Naga Chalasani, MD currently serves as an Associate Professor of Medicine at Indiana University School of Medicine and as the Director of its Division of Gastroenterology and Hepatology. He is a clinical hepatologist by training and in practice and is board certified in internal medicine, gastroenterology and hepatology, and transplant hepatology CAQ. He was educated at the Andhra Loyola College in India (biology 1979-81) and the Kakatiya Medical College (MB, BS 1988), after which he served as an internal medical resident at Emory University in Atlanta (1991-4). He followed with a fellowship in gastroenterology and hepatology at Emory (1994-7). Subsequently he relocated to Indiana University School of Medicine where he remains to date. He was elected to Alpha Omega Alpha, 1993; received the Dupont Young Investigator’s Award 1993; IUSM Young Investigator of the Year, 2002; American Society of Clinical Investigation, 2008. He has published over 100 original manuscripts and dozens of review articles and text book chapters. He is the PI for the NIDDK-funded DILIN Clinical Center and NASH CRN Clinical Center at Indiana University.
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Date created: April 29, 2008 |
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