Liver Function Tests

1. Liver Function Tests

4. What are “Liver Function Tests” • Few are truly associated with function • Albumin: protein synthetic function • INR: clotting factor synthesis • Most are related to cell injury • Patterns point to specific cell injury

5. Tests of Liver Injury • AST/ALT • Cytoplasmic enzymes found in hepatocytes • Very sensitive marker for hepatocyte injury • Specificity is poor (other sources, e.g. muscle) • Mitochondrial isoenzyme • AST increased by ethanol (explains 2:1 ratio) • Alkaline Phosphatase/GGT • Canicular enzymes • Gradual increase in plasma levels with obstruction of canicular flow

6. Patterns of Enzyme Elevation • Hepatocellular injury • AST/ALT • Cholestatic • Bilirubin/alkaline phosphatase • Mixed • Isolated/predominant alkaline phosphatase elevatioin

7. Caveats to Patterns • Hepatocellular injury • Also results in release of bilirubin • Alkaline phosphatase also found in hepatocyte • Cholestatic • Biliary obstruction can lead to hepatocellular injury • History and Physical guide your thinking!!

8. Patient #1: Suzie Duzie • Presents with two days of fever, abdominal pain, yellow skin, nausea, vomiting. • Labs demonstrate the following: • AST 3210 • ALT 3060 • Alk phos 249 • TBili 6.2 (Direct 4.3) • Albumin 3.1 • INR 1.2

9. What targets the hepatocyte? • Toxins • Alcohol • Medications • Tylenol • Mushrooms • Viral • Hepatitis A/B/C • EBV/HSV/CMV • Ischemia • Severe hypotension • Vasoconstriction • Sepsis • Autoimmune • Wilson’s • Alpha-1 antitrypsin deficiency

10. Degree of elevation points to etiology • >1000 to 2000 • Ischemia • Toxin • Virus • >500 to 1000 • Acute biliary obstruction • <300 • Alcoholic liver disease, cirrhosis, chronic obstruction • AST/ALT>2 and each <300 suggests EtOH or cirrhosis • If >500, unlikely EtOH

11. Back to our patient • Transaminases in the 1000s • Suggests ischemia/toxin/viral • IVDU • Risk of acute Hep B or acute Hep C • Cocaine • Risk of ischemia • Recent infection • Doxycycline

12. Patient #2: ImaHurtin • 40 year-old overweight woman presents with right UQ abd pain, fever, chills. Previous episodes after fatty meals. • Laboratory Studies • AST 67 • ALT 57 • Alk Phos 293 • TBili 4.1 (Direct 2) • Albumin 4 • INR 1

13. Increased Bilirubin • Sources • Increased production • Hemolysis, hematoma reabsorption • Impaired uptake/conjugation • Dubin-Johnson, Gilbert’s • Impaired excretion • Renal failure, biliary obstruction • Conjugated=direct=processed by liver • Unconjugated=indirect=not processed by liver • Fractionation – helpful to assess for unconjugatedhyperbilirubinemia • < 20% direct AND indirect >1.2

14. Biliary Obstruction • Canicular cell injury • Alkaline phosphatase • Liver and bone major sources • Increased synthesis and release in liver disease • Up to 3x normal in variety of liver disease • GGT • Sensitive indicator of canicular cell injury • Parallels alkaline phosphatase increase when of liver origin

15. Causes of Biliary Obstruction • Extrahepatic • Choledocholithiasis • Malignancy • Cholangiocarcinoma • Pancreatic cancer • Gallbladder cancer • Ampullary cancer • Primary sclerosing cholangitis • AIDS Cholangiopathy • Intrahepatic • TPN • Sepsis • Primary sclerosing cholangitis • Primary biliary cirrhosis • Intrahepatic mass

16. How would you like to approach this patient? • Finding the source of obstruction • Ultrasound: good for extrahepatic cause • CT/MRI/ERCP: for both intra or extrahepatic cause • In our patient?

17. Patient #3: Biggie Smalls • 46 young man with history of IVDU and long-standing alcohol use following up in clinic. • Laboratory finding • AST 68 • ALT 37 • Alk phos 194 • TBili 1.3 • Albumin 2.9

18. Mixed Patterns of Elevated Liver Function • Chronic Liver disease • Hepatitis B, Hepatitis C • NASH (Nonalcoholic steatohepatitis) • Alcoholic liver disease • Hemochromatosis • Autoimmune hepatitis

19. Patient#4: Iva Fallen • 72 yo man fell in bathroom. Found the next day. • Laboratory • AST 167 • ALT 58 • Alk phos 127 • TBili 1.8 • Albumin 3.9

20. What else do you want to know? • Where else is AST and ALT found? • How can you look for evidence of muscle injury?

21. Additional Laboratory • CK 7260 • Myoglobin 23390 • UA – 2+ blood, microscopic no RBC • Diagnosis?

22. Isolated or Predominant AlkPhos • Chronic Biliary Disease • Primary biliary cirrhosis • Primary sclerosing cholangitis • Infiltrative disorder • Amyloid • Granulomatous diseases • Metastatic carcinoma • abscesses

23. Last Case: Sue Sadd • 32 yo woman, depressed, “took some pills” a few days ago • Laboratory • AST 1450 • ALT 1620 • Alk phos 242 • TBili 8 (direct 4) • Albumin 2.9 • INR 1.7

24. Fulminant Hepatic Failure • Rapid development of severe acute liver injury with impaired synthetic function and encephalopathy • Previously had a normal liver or had well-compensated liver disease

25. Causes

26. Treatment • Directed therapy • Acetaminophen - mucomyst • Acute fatty liver of pregnancy - delivery of infant • Amanita mushroom poisoning - penicillin and silibinin • Wilson's disease - D-penicillamine • Herpes Simplex Infection – acyclovir • Liver transplant

28. Thank You