Jaundice: Work-up of Liver Disease

1. Jaundice: Work-up of Liver Disease Murray N. Ehrinpreis, M.D. Wayne State University School of Medicine

2. Hepatobiliary System • Liver: most important metabolic organ -Regulates -Metabolizes/processes/detoxifies -Synthesizes -Secretes/excretes (into blood and biliary tree) • Biliary tree: bile ducts/gallbladder -Transports -Stores -Eliminates

3. Hepatobiliary Dysfunction • When one or many of these processes are not functioning normally

4. Symptoms of Liver Disease • Asymptomatic • Fatigue, weakness, malaise • Nausea, vomiting, abdominal pain • Jaundice, dark urine, light stools • Pruritus, xanthomas, xanthalasmas • Ascites, edema, mental status changes

5. Important Aspects of History • Viral hepatitis risks (IDU, transfusion, unprotected/atypical sexual practices, promiscuity, travel, occupation,family history) • Excessive alcohol use • Medications, polypharmacy • Toxic chemical exposure • Herbal medications

6. Physical Findings • Jaundice, icterus • Hepatomegaly, hepatic tenderness, firm/hard/nodular liver • Splenomegaly • Ascites, edema, prominent abdominal veins • Gallbladder palpable • Scratch marks, xanthomas/xanthalasmas, spider angiomas, palmar erythema • Ecchymoses, petechiae

7. Important Hepatobiliary Blood Tests • Hepatocellular disease -AST (SGOT) -ALT (SGPT) this is more specific for liver • Cholestatic disease -Alkaline phosphatase -5’-nucleotidase • General -Bilirubin (total and direct) -Albumin -Prothrombin time -GGT (GGTP) this test is too sensitive

8. ANA (anti-nuclear antibody) AMA (anti-mitochondrial antibody) Viral hepatitis serologies (for A, B, C) Hepatitis viral titers (B, C) -fetoprotein CA-19-9 Ferritin Ceruloplasmin 1-antitrypsin Other Important Bloods

9. Abdominal ultrasound Abdominal CT Abdominal MRI MRCP ERCP PTC Liver biopsy Paracentesis TIPS Important Hepatobiliary Procedures

10. Sequential Approach to Evaluation of Hepatobiliary Disease • History and Physical • Laboratory Tests • Imaging • Liver Biopsy

11. Jaundice

12. Bilirubinuria

13. Sources of Bilirubin

14. Bilirubin Pathway

15. Hemolytic Jaundice

16. Gilbert’s Syndrome-decreased uptake AND decreased conjugation

18. Ways That Things Can Go Wrong with the Liver • Hepatocellular disease: disease due primarily to loss of function and death of hepatocytes (liver parenchymal cells) • Cholestasis: disease due primarily to decreased bile flow from either liver cell dysfunction or biliary tree abnormalities • Mixed: liver conditions that have features of both of the above • Cirrhosis: cellular loss, scarring, altered architecture and blood flow

19. Hepatocellular Necrosis and Inflammation-”Hepatitis” • Causes: acute and chronic --Viral, bacterial --Autoimmune --Drugs, toxins --Metabolic disorders --Ischemia --Others

20. Presentation-Hepatocellular Injury • Asymptomatic • Non-specific: fatigue, malaise, anorexia, nausea, vomiting, abdominal discomfort, fever • Specific: jaundice, dark urine, light-colored stools • Disease specific: urticaria, arthritis, rash, lymphadenopathy

21. Jaundice in Hepatocellular Necrosis • Conjugated hyperbilirubinemia • Despite loss of hepatocytes, remaining cells have great excess capacity to conjugate • Excretion of conjugated bilirubin is rate-limiting step

22. Aminotransferase Elevation in Hepatocellular Necrosis

24. Percutaneous Liver Biopsy

25. Liver Biopsy

26. Severe Liver Injury • Hypoglycemia • Serum amino acid alterations • Hyperammonemia • Blood/brain barrier abnormalities • Coagulopathy • Deep jaundice

28. Presentation of Acute Hepatic Failure • Jaundice • Mental status changes • Seizures • Hypoglycemia • Cerebral edema • Bleeding/bruising • Lactic acidosis • Renal failure

29. Head CT-Cerebral Edema

30. Treatment of Hepatocellular Disease • Supportive-rest, diet, fluids, etc. • Discontinue toxic drug or hepatotoxin • Anti-viral agents/Interferon-chronic Hepatitis B & C, HSV, CMV • Corticosteroids/immunosuppressives-autoimmune disease • Liver transplant-acute/chronic hepatic failure

31. Prevention of Hepatocellular Disease • Vaccines • Sanitation/work safety • Universal precautions • Safe sex • Healthy habits • Blood/blood product testing • Careful use of pharmaceuticals/herbals

32. Cholestasis-decreased bile flow • Extrahepatic (“surgical,” “mechanical,” “obstructive”): gallstones, tumors, strictures, atresia • Intrahepatic (“medical”): drugs, toxins, metabolic, infectious, inflammatory

34. Cholestasis: Presentation • Asymptomatic: Alkaline phosphatase elevation in serum • Symptomatic: -Jaundice -Pruritus -Coagulopathy -Malabsorption -Osteoporosis -Xanthomas/xanthalasmas

35. Cholestasis: Signs • Icterus • Skin excoriation • Ecchymoses • Xanthomas/xanthalasmas • Acholic stool • Hepatomegaly • Dilated gallbladder

36. Jaundice with Cholestasis-”Obstruction” could be in the hepatocyte (cellular dysfunction), too

37. Acholic Stool

38. Xanthomas

43. CT Scan-Biliary and Pancreatic Obstruction. Ultrasound gives similar information.

44. Technique of ERCP

45. ERCP. MRI (MRCP) can give a good image of the biliary system, but does not allow other diagnostic or therapeutic interventions

46. Biliary Stent

47. ERCP/Sphincterotomy (for stone removal or large stent placement)

48. Cirrhosis • Hepatic fibrosis severe • Altered hepatic architecture • Regenerative nodules • Abnormal hepatic blood flow • Portal hypertension • Porto-systemic blood shunting

49. Causes of cirrhosis • Chronic hepatitis, viral and otherwise • Alcohol • Metabolic disorders (hemochromaosis, Wilson’s disease, steatohepatitis) • Chronic biliary obstruction • Drugs, toxins • Other genetic, congenital,idiopathic diseases

50. Cirrhotic liver and congested spleen