Abnormal Liver Tests

1. Abnormal Liver Tests Harry Colt, MD 9/4/07

3. Objectives

4. Why is this important? one of the common problems in everyday clinical practice sorting out the cause, can initially seem puzzling knowledge of the pathophysiology of the enzymes and patterns of abnormalities are helpful

6. Evaluation of Abnormal liver test includes history physical analysis of enzyme pattern 1. hepatocellular or cholestatic 2. magnitude of abnormality 3. rate of change further testing

7. History

8. History (cont�d)

9. Physical jaundice, hepatomegaly, ascites, RUQ tenderness, palmar erythema, spider nevi, asterixis, encephalopathy

10. Pattern of Liver Enzyme Elevation Hepatocellular or cholestatic? Magnitude of change? Rate of change?

11. Hepatocellular (aminotransferases) not liver �function� tests sensitive indicators of liver cell injury released when liver cell membrane damaged AST found in liver, cardiac muscle, skeletal muscles, kidneys, brain, pancreas ALT found in liver, skeletal muscle

13. Causes of Hepatocellular Pattern alcohol induced liver injury medications (prescriptions, OTC, drugs, herbs chronic Hepatitis B chronic Hepatitis C autoimmune hepatic steatosis (fatty liver) hemochromatosis Wilson�s disease alpha-one antitrypsin deficiency celiac disease

14. Non-Liver Causes of Hepatocellular Pattern inherited disorders of muscle metabolism Acquired muscle disease strenuous exercise

16. Initial Tests (Hepatocellular) Hep C antibody Hep B Sag (Hep B SAb, Hep B Cab) Fe, TIBC SPEP *increased polyclonal immunoglobulins suggest autoimmune hepatitis *low alpha one globulin suggests alpha one antitrypsin deficiency ----------------------------------------------------------- Ceruloplasmin (<40 yo)

17. Additional Tests (Hepatocellular) PCR for Hep C RNA alpha one antitrypsin phenotyping antiendomysial and antigliadin Ab ultrasound liver biopsy

18. Alcoholic Liver Disease AST> ALT (at least 2:1) if AST twice ALT, 90% have alcoholic liver disease if AST 3x ALT, 96% have alcoholic liver disease only rarely in alcoholic liver disease is AST >8x normal or ALT >5x normal

21. Hepatitis C 4 million Americans Hep C antibody positive 3 million chronically infected (Hep C virus RNA present) risk factors: blood transfusions, IV drug use, tattoos/body piercing, high risk sexual activity, work duties initial test: Hep C Ab (92-97% sensitivity) if positive, confirm with PCR for Hep C virus RNA if positive for RNA, consider liver biopsy if Hep C and fibrosis, usually treat

22. Hep B tests: Hep B Sag, Hep B SAb, Hep B Cab Hep B Sag positive, Hep B Cab positive Hep B Hep B SAb positive, Hep B Cab positive immune to Hep B if Hep B Sag positive, do Hep B e antigen and Hep B virus DNA if Hep B virus DNA and Hep e antigen present, consider liver biopsy and treatment

23. Autoimmune Hepatitis primarily young to middle aged women ?:? = 4:1 80% of those with autoimmune hepatitis have hypergammaglobulinemia on SPEP liver biopsy is necessary for diagnosis important: amenable to treatment

24. Hepatic Steatosis and Nonalcoholic Steatohepatitis usually only mild elevation of aminotransferases AST:ALT usually less than 1:1 ultrasound or CT can identify this diagnosis of nonalcoholic steatohepatitis requires liver biopsy steatosis has benign course nonalcoholic steatohepatitis can progress to cirrhosis weight loss is key to treatment

25. Hemochromatosis common genetic disorder, autosomal recessive; homozygote frequency 1:300 excessive GI absorption of iron, and subsequent iron deposition in heart, lung, skin screening test: Fe, TIBC if Fe/TIBC >45%, consider hemochromatosis if abnormal, liver biopsy important to diagnose for both individual and family

26. Wilson�s Disease Rare genetic disorder (1:30,000-1:300,000) of biliary copper excretion Usually onset before age 25, but consider up to age 40 Suspect if psych/neuro problems Screen with ceruloplasmin, reduced in 85% Also diagnosed by Kayser-Fleischer rings 24 hour urine for copper excretion � excretion of >100?g suggests Wilson�s Confirm by liver biopsy

27. Alpha-one Antitrypsin Deficiency 1:1600-1:2800, suspect if pulmonary disease Screen by diminished alpha globulin on SPEP or direct measurement of alpha-one antitrypsin Confirm by phenotype determination

28. Non-Hepatic Causes If other causes ruled out, consider celiac sprue Test for antigliadin or antiendomysial antibodies Acquired and congenital muscle disorders and strenuous exercise can cause elevated hepatocellular enzymes if muscle disorder suspected, check CPK and aldolase which should be elevated

29. If ALT & AST elevated, but all other blood tests normal? If AST, ALT <2x normal, observe If AST, ALT >2x normal, biopsy

36. Causes of Elevated Alk Phos Alk phos can come from liver, bone, placenta, intestine (rare) Alk phos higher in children, pregnant women First goal is to: identify the source (liver vs bone) Methods: 1. Alk phos fractionation 2. GGT

37. Causes of Elevated Alk Phos If liver source established, suspect cholestasis or infiltrative liver disease Causes include: partial obstrction of bile ducts, primary biliary cirrhosis, sclerosing cholangitis, certain drugs (eg, steroids), sarcoidosis, granulomatous disease, metastatic cancer

38. How to distinguish these entities? Next step ultrasound antimitochondrial antibodies (suggestive of primary biliary cirrhosis)

40. Other Liver Tests GGT Very sensitive for hepatobiliary disease, but low specificity Fallen out of favor except as confirmatory test BILIRUBIN Unconjugated huperbilirubinemia caused by increased bilirubin production or decreased hepatic uptake Most common causes of unconjugated hyperbilirubinemia: Gilbert�s (5%), hemolysis

41. Tests of Liver Function

42. Tests for Liver Function (cont�d) 2. INR Prolonged by end stage liver disease, warfarin, vitamin K deficiency INR dependant on clotting factors which have half life of one day More sensitive indicator of liver synthetic function

53. Resources