1 / 45

Approach to Abnormal Liver Tests

Approach to Abnormal Liver Tests. Anne Larson, MD Hepatology University of Washington. Case 1 – 65 y/o woman. comes to you to establish care complaints fatigue pruritis dry eyes past history hysterectomy for fibroids 10 years ago no alcohol, tobacco or drug use.

layne
Télécharger la présentation

Approach to Abnormal Liver Tests

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Approach to Abnormal Liver Tests Anne Larson, MD Hepatology University of Washington

  2. Case 1 – 65 y/o woman • comes to you to establish care • complaints • fatigue • pruritis • dry eyes • past history • hysterectomy for fibroids 10 years ago • no alcohol, tobacco or drug use

  3. Case 1 – 65 y/o woman • exam • spider angiomata • mild splenomegaly • otherwise normal

  4. Case 1 – 65 y/o woman • screening labs reveal • platelets 90,000 - alk phos 4x uln • bilirubin normal - albumin 3.3 (nl >3.5) • AST/ALT normal - PT normal • what do you want to do next? • be thinking about this

  5. Case 2 – 43 y/o female • complaining of • 4 days of prolonged, severe RUQ pain • fever, severe nausea, some vomiting • worse after eating • Past History • 20 yr ago began periodic attacks • evening RUQ pain, fluctuating intensity, no fevers • lasting 1-4 hours with residual RUQ tenderness

  6. Case 2 – 43 y/o female • Past History (cont) • during last 8 years, continued episodes • pain more intense and prolonged, accompanied by penetrating pain to back below scapula • marked tenderness in RUQ persisting days • told in the past she had gallstones

  7. Case 3 • Exam • temp 38.5°C pulse 100 uncomfortable/sweating • marked tenderness in RUQ with splinting • (+) Murphy's sign • icterus • bilirubin 6 mg/dl - alk phos 3x nl (~400 U/L) • ALT 100 mg/dl - normal albumin, PT • WBC 28,000 - GGT 150 U/L (nl <45) • how would you proceed?

  8. Approach to Abnormal Liver Tests • If patient is asymptomatic • The First Step: • repeat the tests to confirm the results • make sure to stop all alcohol use

  9. The Diagnosis • No single test is sufficient • No single battery of tests is sufficient

  10. The Diagnosis • Most liver disease can be diagnosed by: • taking a meticulous history • recognizing the pattern of enzyme elevations • rationally selecting a few “second-line” tests and imaging studies

  11. Types of Liver Tests • grouped by the liver function they assess • measures of hepatobiliary cell injury • measures of transport efficiency of organic compounds • measures of hepatic synthetic function

  12. Tests Reflecting Cell Injury • Aminotransferases (ALT & AST) • Alkaline Phosphatases • Transpeptidases • 5’-Nucleotidase

  13. Tests Reflecting Cell Injury • Aminotransferases • Catalyze -amino group transfers • aspartate or alanine  ketoglutarate • indicators of liver cell (hepatocyte) injury • sensitive but not specific • most useful marker of cell inflammation or necrosis • represent a “leak” from damaged cells

  14. Tests Reflecting Cell Injury • Aminotransferases - cont • aspartate aminotransferase (AST) • in cytosol and mitochondria • liver > heart > skeletal muscle > kidneys > brain > pancreas > lungs > WBCs > RBCs • alanine aminotransferase (ALT) • in cytosol • predominantly liver • more sensitive and specific than AST

  15. Tests Reflecting Cell Injury • Aminotransferases – cont. • elevated in nearly all liver diseases (ALT > AST) • marked  is usually hepatocellular disease • levels may/may not reflect extent of damage • do not correlate with eventual outcome • usually <500 in obstructive jaundice • usually parallel each other • AST > ALT with EtOH, fulminant, and pregnancy

  16. Tests Reflecting Cell Injury • Alkaline Phosphatase • catalyzes organic phosphate esters • the enzyme is bound to hepatic canalicular membrane • elevation may be due to induction of enzyme synthesis rather than inability of liver to secrete it into the bile • increases seen with cell injury or obstruction • slight to moderate (1-2x) – usually hepatocellular • large increases (3-10x) – obstruction or cholestasis

  17. Tests Reflecting Cell Injury • Alkaline Phosphatase – cont. • isolated elevations • infiltrative disease – tumor, abscess, granuloma, amyloid • Non-liver causes of elevations: • bone disease » diabetes • chronic renal failure » intestinal disease • renal cancer » genetic (pseudoelevation) • pregnancy » osteitis deformans • sepsis (esp. GNRs) » multiple bone fractures • Hodgkin's disease » intraabdominal infections • hypothyroidism » pernicious anemia • congenital hypophosphatasia » zinc deficiency

  18. Tests Reflecting Cell Injury • -glutamyl transpeptidase (GGT) • catalyzes transfer of -glutamyl groups • high concentrations in bile ductule epithelial cells • useful to exclude “bone” source for Alk Phos • correlates with alk phos levels in liver disease • sensitive but not specific •  in renal failure, MI, pancreatitis, diabetes

  19. Tests Reflecting Cell Injury • GGT – cont. • Causes of elevations: • liver disease » pancreatic disease • alcohol » renal disease • cardiac disease » obesity • radiotherapy » diabetes • drugs – GGT is “inducible” • phenobarbitalanticoagulants • dilantinoral contraceptives • acetaminophentricyclic antidepressants

  20. Tests Reflecting Cell Injury • 5’-Nucleotidase (5NT) • hydrolyzes 5’ phosphates from nucleotides • associated with canalicular and sinusoidal membranes • physiologic function unknown • only hepatobiliary tissue can release 5’-NT • specific for hepatic disease • highest in cholestatic conditions

  21. Tests Measuring Transport Efficiency • Hepatic clearance reflects: • delivery to hepatocyte (blood flow) • uptake by hepatocyte

  22. Tests Measuring Transport Efficiency Hemoglobin (1) Other Tissue Cytochromes, etc. Heme B-Alb (2) Alb

  23. Tests Measuring Transport Efficiency • Hepatic clearance reflects: • delivery to hepatocyte (blood flow) • uptake by hepatocyte • transport within hepatocyte • molecular alterations within hepatocyte

  24. Tests Measuring Transport Efficiency Hemoglobin (1) Other Tissue Cytochromes, etc. Heme B-Alb (2) Alb B (3)  Conjugated (4)  

  25. Tests Measuring Transport Efficiency • Hepatic clearance reflects: • delivery to hepatocyte (blood flow) • uptake by hepatocyte • transport within hepatocyte • molecular alterations within hepatocyte • secretion by hepatocyte into bile • passage down bile ducts into duodenum

  26. Tests Measuring Transport Efficiency Hemoglobin (1) Other Tissue Cytochromes, etc. Heme B-Alb (2) Alb B (3)  Conjugated (4)   Secreted (5) Urine 1% (6) Feces 99%

  27. Tests Measuring Transport Efficiency Hemoglobin (1) Other Tissue Cytochromes, etc. Heme B-Alb (2) Alb B (3)  Conjugated (4)   Secreted (5) Urine 1% (6) Feces 99%

  28. Tests Measuring Transport Efficiency • Remember, hepatic clearance reflects: • delivery to hepatocyte  hemolysis • uptake by hepatocyte  shunts, drugs (i.e., sulfa) • transport within hepatocyte  drugs, genetics • molecular alterations within hepatocyte  genetics • secretion into bile  cell damage, genetics • passage down bile ducts  obstruction

  29. Transport Efficiency • Bilirubin • derived mainly from hemoglobin (95%) • continuous production (300 mg daily) • normal liver reserve can rev up 2-3 times • normal values of “total” bilirubin = 0.1-1.0 mg/dL • conjugated plus unconjugated • direct plus indirect • jaundice evident with levels >3.0 mg/dL

  30. Tests Measuring Transport Efficiency • Types of Bilirubin Direct BilirubinIndirect Bilirubin conjugated unconjugated water soluble lipid soluble polar non-polar seen in urine not in urine

  31. Tests Measuring Synthetic Function • Prothrombin Time (PT) • Albumin • Number Connection Tests / mental status • The liver is the only source of albumin and the prothrombin group of clotting factors

  32. Tests Measuring Synthetic Function • Prothrombin Time (PT) • sick liver can’t make clotting factors • factors 2, 5, 7, 9, 10 (made only in the liver) • prolonged PT reflects failure of liver synthesis • Other causes of prolongation: • congenital deficiencies • consumptive coagulopathies (i.e., DIC) • drugs (i.e., warfarin) • vitamin K deficiency (i.e., dietary,  bile output)

  33. Tests Measuring Synthetic Function • Albumin • most important plasma protein made by the liver • accounts for 65% of protein in serum • half-life ~17-21 days • useful indicator of liver function • Other causes of decrease: • sepsis or multiple organ failure • acute liver failure • dietary

  34. Tests Measuring Synthetic Function • Number Connection Test • liver is site of detoxification • failure leads to toxins in blood • toxins unknown • encephalopathy is sign of liver synthetic failure

  35. The Approach • Important questions to address: • acute vs. chronic (6 months, ?cirrhosis) • hepatocellular vs. cholestatic • asymptomatic vs. symptomatic • ?impaired function • recent insults to the liver? • EtOH, medications, pregnancy, hepatitis, herbs, gallstones, hypotension, toxins

  36. The Approach • Hepatocellular Injury • mainly  AST & ALT +/-  AP, GGT, bilirubin •  2 enzyme elevations  high likelihood of liver dz • guides: • Mild (<3 x normal) • fatty liver, EtOH, chronic hepatitis • Moderate (2-10 x normal) • EtOH, chronic hepatitis, cirrhosis, neoplasm, gallstones • Severe (>10x normal; usually >1,000) • ischemic, viral, toxic (e.g., acetaminophen, herbs)

  37. The Approach • Cholestatic Liver Disease • mainly alkaline phosphatase & GGT +/- bilirubin • determine source of AP • determine fraction of bilirubin elevated • if all indirect, generally not liver • ultrasound and/or CT scan • to rule out obstructive disease, tumors, gallstones

  38. The Approach • Chronic Liver Disease •  6 months of abnormal liver tests • symptoms • asymptomatic – majority of cases • fatigue • arthralgias • pruritis • jaundice

  39. The Approach • Chronic Liver Disease – cont. • Common Causes – 95% of cases: • Hepatitis C - (+) HCV-Ab and HCV-PCR • Hepatitis B – (+) HBsAg and HBV-DNA • Alcoholic liver disease • Hemochromatosis – fasting Fe/TIBC >50%;  ferritin • Autoimmune hepatitis – (+) ANA, (+) ASMA,  IgG

  40. The Approach • Chronic Liver Disease – cont. • Less Common Causes • Primary Biliary Cirrhosis (PBC) - (+) AMA;  IgM • Primary Sclerosing Cholangitis (PSC) – abnormal ERCP • Wilson’s Disease ( ceruloplasmin) • 1-Antitrypsin Deficiency ( 1AT level) • Drugs (i.e., MTX, INH, amiodarone, methyldopa)

  41. The Approach • Chronic Liver Disease – cont. • signs of cirrhosis • spider angiomata • gynecomastia • portal hypertension (caput medusa) • palmar erythema (seen in 10-15% of normal population) • advanced end stage liver disease – refer pronto! • ascites »  albumin • varices »  prothrombin time • encephalopathy

  42. Case • screening labs reveal • platelets 90,000 - alk phos 4x nl • bilirubin normal - albumin 3.4 (nl >3.5) • AST/ALT normal - PT normal • what are the possible diagnoses? • what do you want to do next?

  43. Case 1 • Further lab testing: • HAV (-) HBV (-) HCV (-) • ANA (-) • ASMA (-) • AMA (+) 1:1280 • iron studies normal • ultrasound – splenomegaly, small liver, no bil dil • What Next?

  44. Case • Answer: • primary biliary cirrhosis • just beginning to decompensate  send for OLT

  45. Summary • No ideal study or battery to evaluate liver • abnormal liver tests are often the first sign of liver disease • normal or minimally elevated tests don’t exclude serious disease or cirrhosis • liver biopsy remains the gold standard to detecting and determining cause of disease

More Related