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Liver Function Tests

Liver Function Tests. Steve Bradley Chief Medical Resident, HMC Inpatient Services. 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

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Liver Function Tests

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  1. Liver Function Tests Steve Bradley Chief Medical Resident, HMC Inpatient Services

  2. 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

  3. 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

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

  5. 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!!

  6. 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

  7. 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 What targets the hepatocyte?

  8. 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

  9. 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

  10. Patient #2: Ima Hurtin • 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

  11. 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 unconjugated hyperbilirubinemia • < 20% direct AND indirect >1.2

  12. 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

  13. 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 Causes of Biliary Obstruction

  14. 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?

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

  16. Mixed Patterns of Elevated Liver Function • Chronic Liver disease • Hepatitis B, Hepatitis C • NASH • Alcoholic liver disease • Hemochromatosis • Autoimmune hepatitis

  17. 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

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

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

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

  21. 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

  22. 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

  23. Causes

  24. 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

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