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Liver failure and jaundice

Liver failure and jaundice. PBL support lecture. Topics. Physiology of jaundice Causes of obstructive jaundice Syndrome of hepatitis Syndrome of cirrhosis Causes of liver disease Viral hepatitides . To cover. Bilirubin metabolism in detail Clinical tests required

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Liver failure and jaundice

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  1. Liver failure and jaundice PBL support lecture

  2. Topics • Physiology of jaundice • Causes of obstructive jaundice • Syndrome of hepatitis • Syndrome of cirrhosis • Causes of liver disease • Viral hepatitides

  3. To cover • Bilirubin metabolism in detail • Clinical tests required • Imaging US/ MRCP/ ERCP • Liver screening blood tests • Detailed explanations symptoms physiology of • Ascites / Encephalopathy / HRS • Gallstone disease • Psychopathology related to alcohol • Alcohol histories and CAGE questionnaire

  4. Jaundice

  5. Bilirubin metabolism

  6. Key points • Formed as breakdown of haem • Conjugated in the liver • Water soluble • Extricated in the bile • Metabolised in the gut by bacteria • Reabsorbed and excreted in the liver

  7. Causes • Haemolysis • Unconjugated • Hepatic • Assoc with signs of liver failure • Obstructive • Pale stools • Dark urine • Itch

  8. Causes of obstructive jaundice • Obstruction • Within duct • In duct wall • Outside duct • Physiological

  9. Causes of obstructive jaundice • CBD stones • Cancer • Head of pancreas • Cholangiocarcinoma • LN mets • Chronic pancreatitis • Sclerosing cholangitis

  10. Definitions • What is hepatitis ? • Liver inflammation • Not “infection” (necessarily) • Acute vs chronic hepatitis ? • Inflammation persisting > 6 months • Generally useful for viral hepatitis • What is cirrhosis • Fibrosis of the liver • Nodule formation

  11. Obsolete terms • Chronic persistent hepatitis • Chronic lobular hepatitis • Chronic active hepatitis • Replaced by “activity scores”

  12. Hepatitis “map” Acute hepatitis Recovery Fulminant hepatitis Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  13. Acute hepatitis • Typically • Unwell • Jaundice • RUQ pain • Severe • Confusion • Coagulopathy

  14. Blood tests in acute hepatitis • Typically • Raised ALT / AST (often >1,000) • High bilirubin • Severe cases • Coagulopathy • Renal impairment

  15. Hepatitis “map” Acute hepatitis Recovery Fulminant hepatitis Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  16. Chronic hepatitis • Usually low grade inflammation of the liver • Symptoms • often none • Fatigue • Typically • abnormal LFTs (mild elevation ALT) • Screening • Presents with cirrhosis

  17. Hepatitis “map” Acute hepatitis Recovery Fulminant hepatitis Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  18. Fulminant hepatitis • Acute hepatitis with liver failure • Encephalopathy within 28 days of jaundice • Poor prognosis often needs transplantation

  19. Hepatitis “map” Acute hepatitis Recovery Fulminant hepatitis Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  20. Loss of function Jaundice Coagulopathy Decreased drug metabolism Decreased hormone metabolism Increased sepsis Portal hypertension Varices Piles Ascites Encephalopathy Renal failure Cirrhosis

  21. Causes of cirrhosis • Hazardous Alcohol • Chronic hepatitis B + C • Autoimmune liver disease • Haemachromatosis • Wilson's disease • Chronic obstruction

  22. Stigmata of cirrhosis • Palmer erythema • Leuconychia • Spider naevi • Caput medusa • etc

  23. Caput Medusae

  24. Spider Angiomas

  25. Palmar Erythema

  26. “White Nails”

  27. Ascites

  28. Esophageal Varices

  29. “cholestatic hepatitis” • Oxymoron • Typically drug induced • Acute illness similar to acute hepatitis • But LFTs “obstructive”

  30. Hepatitis A • Duration - Chronicity • Modes of spread • Serology • Outcome

  31. Hepatitis A 99% Acute hepatitis 1-2% Recovery Fulminant hepatitis Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  32. Hepatitis A • Faeco–oral spread • Endemic in developing world • Common in childhood • Typical 12 weeks duration • Immunisation possible • Travel • Other liver disease

  33. Clinical illness Infection ALT IgM IgG Viremia Response HAV in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Week

  34. Hepatitis B • Spread • Blood (IVDU, medical) • Sex • Vertical • Endemic in much of Africa and Asia • Worlds second biggest carcinogen • Immunisation

  35. What determines progression to chronic infection • Age • <1year 90% chronic • 1-5 years 30% chronic • >5 years 1-5% chronic • Immunosuppression • Route of infection • Genotype

  36. Hepatitis B 96% Acute hepatitis 1% 70% Recovery Fulminant hepatitis 30% 3% Chronic hepatitis Death Transplantation Increasing fibrosis Cancer Cirrhosis

  37. Hepatitis B cirrhosis prognosis • Determined by rate of fibrosis progression • Biopsies scored • Fibrosis • Inflammatory activity

  38. Acute Hepatitis B Virus Infection with Recovery Symptoms anti-HBe HBeAg Total anti-HBc Titre anti-HBs IgM anti-HBc HBsAg 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure

  39. Progression to Chronic Hepatitis B Virus Infection Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

  40. Hepatitis B serology • Acute • Early rise in anti core IgM • Chronic • Persistent HbsAg >6/12 • HbeAg +ve = immunotolerant • High viral levels = infectious • Normal LFTs • Few liver problems • HbeAb +ve = immunoreactive • Low viral levels = less infectious • ALT raised • Often fibrotic / cirrhotic

  41. Hepatitis B treatment • Acute - none necessary • Chronic • Antiviral • Suppression • ?? duration • Interferon • Immune stimulation

  42. Hepatitis C • Transmission • Blood borne • Medical • IVDU • 10-20% cases no risk factor • (sexual) • (vertical) • No immunisation possible

  43. Hepatitis C 25% Acute hepatitis Recovery Fulminant hepatitis 75% Chronic hepatitis Death Transplantation Increasing fibrosis Cirrhosis

  44. Hepatitis C • Rarely causes symptoms • Screening of • Donors • IVDU • Abnormal LFTs • Testing • Antibodies • PCR

  45. Treatment • Interferon • Based on genotype • Ribavirin

  46. Hepatitis E • Virtually identical to hepatitis A • May cause severe disease in pregnancy

  47. Hepatitis delta • Imperfect virus • No symptoms of its own • Worsens prognosis of hepatitis B • Treat hepatitis B

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