Chronic Hepatitis - Part 2 - Kuwait

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Chronic Hepatitis - Part 2 - Kuwait

  1. 1. Liver Biopsies in Viral Hepatitis: Beyond Grading and Staging Neil Theise, MD. Depts of Pathology and Medicine (Digestive Diseases) Beth Israel Medical Center – Albert Einstein College of Medicine New York City
  2. 2. for further reference: Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach www.neiltheise.com
  3. 3. Role of Liver Biopsy <ul><li>Confirm clinical diagnosis </li></ul>Grade necroinflammation Stage fibrosis
  4. 4. <ul><li>Confirm clinical diagnosis </li></ul>Role of Liver Biopsy Evaluate possible concomitant diseases Grade necroinflammation Stage fibrosis
  5. 5. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul>
  6. 6. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul>
  7. 7. HCV associated steatosis vs. concomitant fatty liver disease
  8. 8. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe
  9. 9. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1)
  10. 10. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1) Steatohepatitis
  11. 11. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1) Steatohepatitis Absent Variable
  12. 12. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1) Steatohepatitis Absent Variable Steatofibrosis
  13. 13. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1) Steatohepatitis Absent Variable Steatofibrosis Absent Variable
  14. 14. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe Distribution Random Zonal (zone 3, progressing to 1) Steatohepatitis Absent Variable Steatofibrosis Absent Variable Lipogranulomas +/- +/-
  15. 15. Case 1 44 year old man with HCV and mild ALT/AST elevations
  16. 19. Case 1: Diagnoses Fibrous septum formation with mixed features of: - chronic hepatitis C (mildly active) - fatty liver disease (? alcoholic vs. non-alcoholic)
  17. 20. Case 1: Diagnoses Fibrous septum formation with mixed features of: - chronic hepatitis C (mildly active) - fatty liver disease (? alcoholic vs. non-alcoholic) Comment: … The amount of steatosis in the specimen is significantly more than is usually seen with hepatitis C alone, implying possible concomitant fatty liver disease…
  18. 21. BUT!!!
  19. 22. Case 1: Diagnoses Fibrous septum formation with mixed features of: - chronic hepatitis C (mildly active) - fatty liver disease (? alcoholic vs. non-alcoholic) Comment: … The amount of steatosis in the specimen is significantly more than is usually seen with hepatitis C alone, implying possible concomitant fatty liver disease; however, it must be kept in mind that hepatitis C itself may lead to insulin resistance in some patients and thus may also be a direct cause of non-alcoholic fatty liver disease in some patients.
  20. 23. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul>
  21. 24. HCV associated iron vs. other 2 ndary causes vs. Hereditary Hemochromatosis (type 1: HFE mutated)
  22. 25. HCV Associated Iron Type I Hereditary Hemochromatosis Severity
  23. 26. Grading of iron <ul><li>Grade 1 – zone 1, some periportal areas </li></ul><ul><li>Grade 2 – zone 1, all periportal areas </li></ul><ul><li>Grade 3 – zones 1 and 2 </li></ul><ul><li>Grade 4 – zones 1, 2, and 3 </li></ul>
  24. 27. HCV Associated Iron Type I Hereditary Hemochromatosis Severity Grade 1/4 to 2/4 Grade 1/4 to 4/4
  25. 28. Example: Type 1 HH <ul><li>46 y.o. man with mild ALT/AST elevations </li></ul><ul><li>Irish-Scottish descent </li></ul><ul><li>Ferritin 1700  gm/ L </li></ul><ul><li>Iron saturation 89% </li></ul><ul><li>dry weight iron 18,528  gm/ g </li></ul><ul><li>Hepatic iron index 4.2  mol/ gm/ yr </li></ul><ul><li>HCV negative </li></ul><ul><li>1 drink/ day </li></ul>
  26. 31. Case 2 56 year old man referred for HCV and mild liver test elevation
  27. 37. Case 2: Diagnoses <ul><li>Chronic hepatitis, mildly active with transition to cirrhosis (modified </li></ul><ul><li>Ishak stage 3/4), compatible with hepatitis C. </li></ul><ul><li>  </li></ul><ul><li>Hemosiderosis, grade 1/4, ? Hereditary vs. secondary hemochromatosis </li></ul>
  28. 38. Case 2: Diagnoses <ul><li>Chronic hepatitis, mildly active with transition to cirrhosis (modified </li></ul><ul><li>Ishak stage 3/4), compatible with hepatitis C. </li></ul><ul><li>  </li></ul><ul><li>Hemosiderosis, grade 1/4, ? Hereditary vs. secondary hemochromatosis </li></ul><ul><li>Comment: … </li></ul><ul><li>Prussian blue stain highlights increased hepatocyte iron stores in some, but not all periportal regions. This relatively small amount does not exclude a diagnosis of hereditary hemochromatosis due to the variable penetrance of that disease. Genetic testing may be helpful. </li></ul>
  29. 39. Secondary iron overload <ul><li>Cirrhosis (non-biliary) </li></ul><ul><li>Alcoholic liver disease </li></ul><ul><li>NAFLD </li></ul><ul><li>HCV </li></ul>
  30. 40. Secondary iron overload <ul><li>Cirrhosis (non-biliary) </li></ul><ul><li>Alcoholic liver disease </li></ul><ul><li>NAFLD </li></ul><ul><li>HCV: the virus itself…? but also treatment related…? </li></ul>
  31. 41. Secondary iron overload <ul><li>Cirrhosis (non-biliary) </li></ul><ul><li>Alcoholic liver disease </li></ul><ul><li>NAFLD </li></ul><ul><li>HCV: the virus itself…? but also treatment related…? </li></ul>Increased Hepatic Iron Deposition Resulting From Treatment of Chronic Hepatitis C With Ribavirin Fiel MI et al. Am J Clin Path 2000 Jan;113(1):35-9.
  32. 42. HCV and iron <ul><li>Increased degree of inflammation </li></ul><ul><li>Increased degree of fibrosis </li></ul><ul><ul><li>More fibrosis at younger age, especially if homozygous </li></ul></ul>
  33. 43. HCV and iron <ul><li>Increased degree of inflammation </li></ul><ul><li>Increased degree of fibrosis </li></ul><ul><ul><li>More fibrosis at younger age, especially if homozygous >> Pre-Tx phlebotomy? </li></ul></ul>
  34. 44. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul><ul><li>Small cell change </li></ul><ul><li>Iron free foci </li></ul>
  35. 45. HCV + HIV? On HAART: In large cohorts, possibly more aggressive, but individual biopsies look the same as HCV alone. Beware: drug toxicity
  36. 46. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease.
  37. 47. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease. Rare: fibrosing cholestatic hepatitis
  38. 48. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease. Rare: fibrosing cholestatic hepatitis Beware: Infiltrating neoplasms, granulomas, HSV, CMV, biliary tract disease, etc.
  39. 49. Role of Liver Biopsy <ul><li>Confirm clinical diagnosis </li></ul>Stage necroinflammation Evaluate possible concomitant diseases Assess features of HCC risk Grade fibrosis
  40. 50. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul>
  41. 52. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul>Probably malignancy associated , NOT directly pre-malignant
  42. 53. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul><ul><li>Small cell change </li></ul>
  43. 55. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul><ul><li>Small cell change </li></ul>Generally thought to be directly pre-malignant.
  44. 56. Liver Biopsy in Viral Hepatitis: beyond grading and staging… <ul><li>Other diseases </li></ul><ul><li>HCC risk screening </li></ul><ul><li>Fatty liver disease </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>HIV co-infection </li></ul><ul><li>Large cell change </li></ul><ul><li>Small cell change </li></ul><ul><li>Iron free foci </li></ul>
  45. 57. Case 3 52 year old woman with HCV and mild LFT elevation. Mass lesion noted on USG – attempted biopsy of lesion.
  46. 61. Case 3: Diagnoses <ul><li>Chronic hepatitis, mildly active with marked portal fibrosis </li></ul><ul><li>(modified Ishak stage 1/4), compatible with hepatitis C. </li></ul><ul><li>- Large cell change. </li></ul><ul><li>Small cell change. </li></ul><ul><li>Lipogranuloma. </li></ul>
  47. 62. Case 4 61 year old Chinese woman with HBV (low serum HBV DNA)
  48. 71. Case 4: Diagnoses <ul><li>Chronic hepatitis, mildly active with cirrhosis (modified </li></ul><ul><li>Ishak stage 4/4) and possible features of regression, </li></ul><ul><li>compatible with hepatitis B. </li></ul><ul><li>Hemosiderosis, grade 3/4 to 4/4, ? Cirrhosis-associated </li></ul><ul><li>vs. hereditary. </li></ul><ul><li>- Large cell change. </li></ul><ul><li>Small cell change. </li></ul><ul><li>Iron free foci. </li></ul>
  49. 72. Role of Liver Biopsy <ul><li>Confirm clinical diagnosis </li></ul>Stage necroinflammation Evaluate possible concomitant diseases Assess features of HCC risk Grade fibrosis
  50. 73. ?

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