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Approach to Elevated LFT’s

Learn about managing elevated liver enzymes, identifying liver disease, role of primary care, and peak Hepatitis C epidemic. Understand the rise in NAFLD, cirrhosis epidemiology, and clinical cases.

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Approach to Elevated LFT’s

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  1. Approach to Elevated LFT’s Miguel H. Malespin M.D. Assistant Professor, Department of Medicine Medical Director, Hepatology Department of Medicine, Division of Gastroenterology and Hepatology

  2. Disclosures • Consultant for Gilead Pharmaceuticals

  3. Learning Objectives • Describe the prevalence of liver disease within the United States • Review interpretation of abnormal liver enzymes • Develop an approach to managing elevated liver enzymes

  4. Critical Role of Primary Care • Elevated liver transaminase levels are found in up to 8.9% of patients seen in primary care clinics 1,2 • Approximately 9% of patients with elevated liver enzymes are asymptomatic 3,4

  5. Why is identification of patients with abnormal liver enzymes important?

  6. Peak of the Hepatitis C Epidemic • Prevalence of HCV within the United States is ~1.6% 5 • Making it the most common bloodborne pathogen in the United States • Estimated 4 and 7 million persons 6,7

  7. Rising Prevalence of Elevated Liver Enzymes • Nearly ½ of persons with chronic HCV are unidentified • Normal liver enzymes are found in 25–30% of chronic HCV carriers 8 • Institution of screening for baby boomers born between 1945-1965

  8. Currently at the peak of the HCV epidemic2

  9. Hepatitis C surpassed HIV as a cause of virus-related death in 2006

  10. Incidence of Hepatitis C8 http://www.cdc.gov/hepatitis/statistics/

  11. Second Culprit on the Loose…

  12. Insulin Resistance

  13. Diabetes is an important risk factor for progression of fibrosis11,12

  14. Obesity Epidemic • Coincides with the rise in NAFLD

  15. Rising Prevalence of NAFLD10

  16. Epidemiology Related to Cirrhosis • Prevalence of cirrhosis in the United States is estimated to be ~0.27 percent of the population • 633,323 Adults 13 • Nearly 2 million deaths annually are attributable to CLD and cirrhosis 14 • 12th leading cause of death

  17. Epidemiology of Cirrhosis • Total number of persons with cirrhosis is estimated to peak at 1 million in 202015 • Rates of hepatic decompensation and hepatocellular carcinoma are expected to increase for another 10 to 13 years15

  18. Over time, there has been an increase in mortality from liver disease2

  19. Normal transaminases do not exclude the presence of chronic liver disease • Fluctuation in transaminase levels occur • Particularly in patients with chronic HBV, HCV, and NASH • “Burned out cirrhosis” • Poor sensitivity/specificity • 19,877 asymptomatic US Airforce basic trainees, 99 were found to have abnormal ALT elevation, 12 were positive for liver disease 16

  20. What are LFT’s? • Serologic measurements ordered to evaluate for liver disease • The term liver function tests are actually a misnomer • Serum aminotransferases (ALT/AST) reflect inflammation • Alkaline Phosphatase (AP) reflects biliary injury • Bilirubin, albumin, and PT/INR more accurately reflect hepatic function

  21. Why are LFT’s ordered? • Routine check-up • Drug monitoring • Symptoms • Screen for liver disease

  22. General Approach • What is the liver trying to tell me? • Does this appear to be acute or chronic? • If chronic, do findings exist that are concerning for advanced fibrosis/cirrhosis

  23. Elevated Aminotransferases • Good indicators of hepatocellular injury • Serum glutamic oxaloacetic transaminase (SGOT) • AST is located in the cytosol and mitochondria • Also present in striated muscle, the kidney, brain, pancreas, lung, leukocytes, and erythrocytes • Serum glutamic pyruvic transaminases (SGPT) • ALT lies in the cytosol • More specific indicator of liver injury

  24. Normal Values • AST <37 IU/L or ALT <40 IU/L for men • AST or ALT <31 IU/L for women

  25. Elevated Aminotranferases • Elevated aminotransferase levels are present in 7.9% of the population when sampling asymptomatic individuals 17 • Some of the most common identifiable causes include: 18 • alcohol use (13.5%) • hepatitis C (7.0%) • hemochromatosis (3.4%) • hepatitis B (0.9%) • combination of causes (6.1%)

  26. Table 1. Causes of elevated aminotransferases. a Aminotransferase level increase of 5-10 x upper limit of normal b Aminotransferase level increase of >10 x upper limit of normal cBilirubin increase of <5 x upper reference limit

  27. Clinical Case #1 • 45 year old male with a history of alcohol abuse and chronic back pain for which he takes 3 Norco tablets a day presents with jaundice, nausea, malaise and abdominal pain. Total bilirubin 3.5 ALT 5344 Direct bilirubin 2.7 AST 3923 Alkaline phosphatase 240 INR 1.3

  28. Clinical Case #1 • RUQ US: normal liver contour • Acetaminophen level: <1 • ANA: Normal • ASMA: Normal • Hepatitis B surface antigen Positive • Hepatitis B core IgM Positive

  29. Clinical Case #2 63 year old female with a history of obesity, hypertension, diabetes who presents for evaluation of elevated liver enzymes. ALT 64 Platelet Count 110 AST 53 INR 1.1 AP 90 TB 1.0 Physical Exam: Evidence of spider angiomas and palmar erythema

  30. Clinical Case #2 • Ultrasound splenomegaly, steatosis • ANA normal • ASMA normal • Ferritin 500 • Iron/TIBC 24 • A1AT Normal • HBsAg Negative • Hepatitis C antibody positive

  31. General Approach • Obtain baseline right upper quadrant ultrasound to evaluate for liver lesions, hepatic morphology, thrombus, splenomegaly • Obtain baseline labs to evaluate for acute/chronic liver disease • Referral to GI/Hepatology

  32. Alkaline Phosphatase/Gamma-glutamylTransferase (GGT) • ALP • Produced predominantly in the liver and bone • Can be found in renal, intestinal, placental tissue, or within leukocytes • GGT/ALP Fractionation • It has a high sensitivity for hepatobiliarydisease • Elevated GGT levels also occur in alcohol-related liver disease • Most useful when elevated alkaline phosphatase levels occur with otherwise normal liver enzymes and bilirubin levels

  33. Clinical Case #3 • 45 year old female presents for evaluation of elevated liver enzymes. She denies abdominal pain. ALT 45 AST 39 ALP 650 TB .9 INR .8

  34. Clinical Case #3 • Denies medication or recent antibiotic use • Denies alcohol use • RUQ US negative • Hep b sAg negative • HCV Ab negative • ANA/ASMA negative • AMA positive

  35. Real LFT’s • Bilirubin • PT/INR • Albumin

  36. Bilirubin Metabolism

  37. Clinical Case #4 • 33 year old female with a BMI 32 presents to clinic for evaluation of jaundice and right upper quadrant pain. ALT 55 AST 49 AP 233 TB 3.5

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