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. for further reference: Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach www.neiltheise.com

7. HCV associated steatosis vs. concomitant fatty liver disease

8. HCV Associated Steatosis Concomitant Fatty Liver Disease (ALD or NAFLD) Severity Mild Mild, Moderate or Severe

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. 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. 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. 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. 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. 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. Case 1 44 year old man with HCV and mild ALT/AST elevations

19. Case 1: Diagnoses Fibrous septum formation with mixed features of: - chronic hepatitis C (mildly active) - fatty liver disease (? alcoholic vs. non-alcoholic)

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…

21. BUT!!!

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.

24. HCV associated iron vs. other 2 ndary causes vs. Hereditary Hemochromatosis (type 1: HFE mutated)

25. HCV Associated Iron Type I Hereditary Hemochromatosis Severity

27. HCV Associated Iron Type I Hereditary Hemochromatosis Severity Grade 1/4 to 2/4 Grade 1/4 to 4/4

31. Case 2 56 year old man referred for HCV and mild liver test elevation

45. HCV + HIV? On HAART: In large cohorts, possibly more aggressive, but individual biopsies look the same as HCV alone. Beware: drug toxicity

46. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease.

47. HCV + HIV? Untreated: Often more severe activity. Often more advanced disease. Rare: fibrosing cholestatic hepatitis

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.

57. Case 3 52 year old woman with HCV and mild LFT elevation. Mass lesion noted on USG – attempted biopsy of lesion.

62. Case 4 61 year old Chinese woman with HBV (low serum HBV DNA)

73. ?