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Work up of the Asymptomatic Patient with Liver Enzyme Abnormalities

Work up of the Asymptomatic Patient with Liver Enzyme Abnormalities. G.Y. Minuk Professor of Medicine and Pharmacology University of Manitoba Head, Section of Hepatology Health Sciences Centre Winnipeg, Manitoba April 10, 2008. Questions. Does the Patient have Liver Disease?

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Work up of the Asymptomatic Patient with Liver Enzyme Abnormalities

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  1. Work up of the Asymptomatic Patient with Liver Enzyme Abnormalities G.Y. Minuk Professor of Medicine and Pharmacology University of Manitoba Head, Section of Hepatology Health Sciences Centre Winnipeg, Manitoba April 10, 2008

  2. Questions • Does the Patient have Liver Disease? • Is the Disease Hepatocellular, Cholestatic or Mixed? • Differential Diagnosis? • Is the Problem Urgent and when to refer to a specialist?

  3. Why, who and how?

  4. >2x ULN 4.4% 1-2x ULN 9.6% <ULN 86% Aminotransferase Elevations in the General Population Lee et al., Hepatology 2008

  5. Fig. 2. Kaplan Meier survival of Olmsted County residents by ALT results. * Indicates P 0.01 in comparison with the ULN group in each panel. Lee et al. Hepatology 2008;47:880-887

  6. Fig. 3. Relative risk of death according to the aminotransferase level. Lee et al. Hepatology 2008;47:880-887

  7. Message • Aminotransferase abnormalities are common (~ 15%). • Elevated aminotransferases are associated with increased mortality.

  8. Liver Enzyme Tests Alanine Aminotransferase (ALT) Aspartate Aminotransferase (AST) Alkaline Phosphatase (AP) Gamma Glutamyltransferase (GGT) Liver Function Tests Albumin Bilirubin INR Suggested Screening Profile:

  9. 1) Does the Patient have Liver Disease?

  10. 40 36% 35 31% 30 25 20 15 10 5 0 ALT AST Reproducibility of Initially Abnormal ALT/AST Values Percent Lazo et al., Ann Intern Med, 2008; 148; 348-52

  11. Increased ALT in Absence of Liver Disease-Time of Day Cordoba J et al. Hepatology 1998

  12. Increased ALT in Absence of Liver Disease -Time of Day Cordoba J et al. Hepatology 1998

  13. 20 18% 18 16 14 12% Percent 12 10 8 6 4 2 0 AP GGT Reproducibility of Initially Abnormal AP/GGT Values Lazo et al., Ann Intern Med, 2008; 148; 348-52

  14. Elevated Alkaline Phosphatase in the Absence of Cholestasis • Length of tourniquet application • Delay in separation of sera • Fatty meals in blood groups A and O (secretors of ABH red-cell antigens) • Albumin infusions • Regan Isoenzyme

  15. Message • Repeat abnormal LFTs within 2-3 wks and preferably in the AM.

  16. Does the Patient have Liver Disease?

  17. “Liver” Function

  18. Functional Heterogeneity of Liver Lobule Albumin INR Bilirubin

  19. Does the Patient have Liver Disease? Yes if : • If the abnormality is reproducible within a short time frame. • ALT increased (in absence of rhabdomyolysis). • Alkaline Phosphatase and GGT increased. • Combination of any two liver enzyme and/or function tests are abnormal.

  20. Is the Disease Hepatocellular, Cholestatic or Mixed? ALT <40 Alk Phos <120

  21. Differential Diagnoses of Hepatocellular Liver Injury (Hepatitis)

  22. Cholestasis

  23. Differential Diagnosis of Intrahepatic Cholestasis

  24. Differential Diagnosis of Mixed Liver Enzyme Abnormailites • Drugs • Infection (HCV and CMV) • Infiltrative Disorders (granuloma, tumor)

  25. Is the Problem Urgent and when to refer to a specialist? Moser et al Dig Dis Sci 2001

  26. Is the Problem Urgent and when to refer to a specialist? • Hepatic dysfunction (elevated INR and/or decreased albumin, increased bilirubin -in absence of cholestasis). • Cholestatic enzyme pattern and dilated ducts on ultrasound. • Space occupying lesions on imaging (other than hemangioma or simple cysts). • In absence of “urgency”, refer when enzyme abnormalities persist beyond six months without a diagnosis.

  27. Exceptions

  28. Normal ALT in Presence of Hepatocellular Injury -Delay in Testing

  29. Normal ALT in Presence of Hepatocellular Injury - Pyridoxine Deficiency Ludwig S & Kaplowitz N. Gastroenterology 1980

  30. Normal AST in Presence of Hepatocellular Injury Cohen G et al. Ann Int Med 1976

  31. Normal Alkaline Phosphatase in the Setting of Cholestasis

  32. Questions

  33. 1) Does the Patient have Liver Disease?

  34. Does the Patient have Liver Disease?

  35. Elevated Alkaline Phosphatase in the Absence of Cholestasis Wilson JW. N Engl J Med 1979

  36. Summary • Who: Biochemical screening for liver disease should be offered to all patients at each annual evaluation. • Why: Increased serum aminotransferase levels are associated with decreased 10 year survival rates. • How: A complete set of morning liver enzyme and function tests.

  37. Increased ALT in Absence of Liver Disease • High Sucrose Diets* • Erythromycin* • Diabetic ketoacidosis* * Colorimetric assay

  38. Who and why? Lee et al. Hepatology 2008;47:880-887

  39. Alcohol induced liver disease Ischemic Liver Cirrhotic Liver Normal ALT in Presence of Hepatocellular Injury- Ischemic hepatitis

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