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CREDIT

BRIEF QUESTIONS AND ANSWERS Qt How should a patient with an isolated ON CURRENT CLINICAL GGT elevation be evaluated? CONTROVERSIES

WILLIAM D. CAREY, MD ly ) come from the Professor of Medicine, Ohio State University; head. Section of Hepatology, Department of Gastroenterology, Cleveland Clinic or a nonhepatic source such as the bones or placenta.5 Only if alkaline phosphatase and

# DO NOT BECOME overly concerned GGT are both elevated—but the other liver A• about it. Isolated GGT (gamma glu- enzymes are not—does the GGT provide tamyl transpeptidase) elevations are common, important utility.4 If both alkaline phos- and do not indicate serious or progressive liver phatase and GGT are elevated, at least a por- disease. No specific evaluation apart from a tion of the alkaline phosphatase is of hepato- history and physical examination is needed. biliary origin. Conversely, if the GGT level is Although GGT is elevated in a number of normal, the alkaline phosphatase elevation liver conditions, in most of them other derives from nonhepatic disease (eg, bone dis- enzymes are elevated as well, and these other ease). Even in this situation, however, compa- enzymes are more diagnostically useful than rable information can be obtained by measur- the GGT. Clinical laboratories should consid- ing alkaline phosphatase isoenzymes. er removing GGT from the panel of bundled Although GGT has been shown to rise liver tests to minimize the number of patients with alcohol consumption and has been used who end up on a merry-go-round of testing as an indirect measure of compliance with prompted by isolated GGT elevations. alcohol abstinence, some experts doubt this correlation is sufficiently constant to permit Do not get on a • GGT LACKS SPECIFICITY GGT levels to serve as a surrogate marker for merry-go-round alcohol consumption.5 As a screening test, the GGT level is very sen- Most often, GGT measurement is includ- of testing sitive but has a very low specificity. GGT is ed as part of a bundled panel of tests. Owing to found in highest concentrations in the liver the limitations of GGT as a test, the (particularly in biliary tubular epithelium), Cleveland Clinic has removed it from its but also in the kidneys, seminal vesicles, pan- "liver panel," as have many other major med- creas, spleen, heart, and brain.1 Elevations of ical centers. Yet the test persists, and many this enzyme occur therefore in a number of clinicians receive GGT results whether they disparate clinical situations,2 including all request them or not. manner of liver disease—fatty liver, viral hepatitis, bile duct obstruction, and most drug • RECOMMENDATIONS reactions involving the liver. What, then, to do if the GGT is elevated but • GGT HAS LITTLE UTILITY the AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phos- The combination erf high sensitivity and very phatase, , and albumin levels are all low specificity seriously hampers the utility of normal? In deciding whether to evaluate the GGT. Clinically, the value of the GGT is mar- liver further, consider the patient's risk factors ginal. If other hepatic enzymes are elevated, for liver disease, symptoms, and physical find- the GGT level provides no incremental infor- ings. mation. • Patients with risk factors for acquired liver GGT measurement is often used to deter- diseases such as hepatitis B and C should have mine if elevations in other enzymes (especial- screening tests for these diseases. Alcohol con-

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sumption should be defined and, if excessive, to inquire again about alcohol consumption, modified. and to recommend moderation in its con- • In men and postmenopausal women, sumption. An obese patient may have fatty screening for iron overload is always appropri- liver, currently only treatable with weight loss, ate (serum , iron, iron-binding capaci- and so in obese patients the need for weight ty, and percent saturation). reduction might be reinforced by pointing to • Patients who are obese, diabetic, or have the GGT elevation. • elevated should have an ultra- sound of the liver, which often reveals signals • REFERENCES characteristic of fatty liver. 1. Goldberg DM. Structural, functional, and clinical aspects • Patients with hepatomegaly, spleno- of y-glutamyl transferase. Crit Rev Clin Lab Sci 1980; 12:1-58. megaly, ascites, or other manifestations of 2. Zein M, Discombe G. Serum gamma glutamyl transpepti- liver disease require further study regardless of dase as a diagnostic aid. Lancet 1970; 2:748-750. the GGT level. 3. Betro MG, Oon RC, Edwards JB. Gamma-glutamyl transpeptidase in diseases of the liver and bone. Am J If the patient has no risk factors or symp- Clin Pathol 1973; 60:672-678. toms and the physical examination reveals 4. Whitfield JB, Pounder RE, Neale G, Moss DW. Serum y- nothing abnormal, an isolated GGT elevation glutamyl transpeptidase activity in liver disease. Gut 1972; 13:702-708. 6 does not require further investigation. The 5. Penn R, Worthington DJ. Is serum y-glutamyl transpepti- test should not be repeated, and it should not dase a misleading test? Br Med J 1983; 286:531-535. trigger imaging studies or a liver biopsy. These 6. Davern TJ, Scharschmidt BF. Biochemical liver tests. In: Feldman M, Sleisenger MH, Scharschmidt BF, Klein S, edi- patients rarely benefit from such add-on test- tors. Sleisenger & Fordtran's Gastrointestinal and Liver ing, nor do they benefit from referral to a gas- Diseases, 6th ed. Philadelphia: W.B, Saunders, troenterologist or hepatologist. They do not 1998:1112-1122. need to have their medications stopped. ADDRESS: William D. Carey, MD, Department of Do discuss the abnormality with the Gastroenterology, S40, The Cleveland Clinic Foundation, 9500 patient, however. This might be a good time Euclid Avenue, Cleveland, OH 44195; e-mail [email protected].

THE CLEVELAND CLINIC 12th Annual FOUNDATION Intensive Review of INTERNAL MEDICINE • •••TTVTT June 19-24, 2000 • Y Y • \ Y • i • • • • Cleveland, Ohio • • Ili • • • • • • m is BOARD-ORIENTED \1\ • A Certification Re-Certification A A* A AAA ••••••• • A A A A A A Case-Driven Format I For course brochure and registration information, Board Simulation I view our website- Sessions j www.clevelandclinicmeded.com Interactive Audience Response HI The Cleveland Clinic Foundation System Department of Continuing Education I 800-762-8173 or 216-444-5696

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