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Autoimmune Liver Diseases: AIH, PBC, PSC Neil Theise, MD Depts. of Pathology and Medicine (Digestive Diseases) Beth Israel Medical Center – Albert Einstein College of Medicine New York City
Autoimmune Hepatitis:
Gender: Mostly female Autoimmune Hepatitis:
Gender: Mostly female Age: 40’s - 60’s Autoimmune Hepatitis:
Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Autoimmune Hepatitis:
Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Presentation: Very severe activity &/or very late stage Autoimmune Hepatitis:
Dynamics of Activity and Progression of Autoimmune Hepatitis over Time Assessment is NOT like chronic viral hepatitis!
Stage of Disease Time Viral hepatitis: Progression vs. activity over time
Stage of Disease Time Autoimmune hepatitis: Progression vs. activity over time
Stage of Disease Biopsy: Advanced disease, but mild or “burned out hepatitis” Autoimmune hepatitis: Progression vs. activity over time
Biopsy: Advancing disease and severe activity Stage of Disease Autoimmune hepatitis: Progression vs. activity over time
Biopsy: Little scarring, but severe activity Stage of Disease Autoimmune hepatitis: Progression vs. activity over time
Stage of Disease Time Autoimmune hepatitis: Progression vs. activity over time No biopsy is likely to show: mild activity and little scarring…
Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Presentation: Very severe activity &/or very late stage Treatment: Immune suppression, transplant for endstage. Autoimmune Hepatitis:
Autoimmune Hepatitis: plasma cells
Perivenular confluent necrosis
Gender: Women Primary Biliary Cirrhosis (PBC):
Gender: Women Age: Middle aged to older Primary Biliary Cirrhosis (PBC):
Gender: Women Age: Middle aged to older Associated diseases:  Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Primary Biliary Cirrhosis (PBC):
Gender: Women Age: Middle aged to older Associated diseases:  Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Serologic markers: AMA (ASMA, ANA) Primary Biliary Cirrhosis (PBC):
Gender: Women Age: Middle aged to older Associated diseases:  Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Serologic markers: AMA (ASMA, ANA) Bile ducts involved: Medium to small ducts ONLY Primary Biliary Cirrhosis (PBC):
PBC, Stage 1: Bile duct injury/loss
 
 
 
PBC, Stage 2: Ductular reaction
 
 
PBC, Stage 3: Fibrosis From portal fibrosis to Transition to cirrhosis…
PBC, Stage 4: Cirrhosis
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
 
PBC AIH
PBC AIH
PBC AIH “ Overlap” Hepatitis
PBC AIH “ Overlap” Syndrome
PBC AIH NRH
Gender: Men Primary Sclerosing Cholangitis (PSC):
Gender: Men Age: Teens to 30’s Primary Sclerosing Cholangitis (PSC):
Gender: Men Age: Teens to 30’s Associated diseases:  Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Primary Sclerosing Cholangitis (PSC):
Gender: Men Age: Teens to 30’s Associated diseases:  Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Primary Sclerosing Cholangitis (PSC):
Gender: Men Age: Teens to 30’s Associated diseases:  Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Ducts involved: Large extrahepatic to small intrahepatic Primary Sclerosing Cholangitis (PSC):
Gender: Men Age: Teens to 30’s Associated diseases:  Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Ducts involved: Large extrahepatic to small intrahepatic At increased risk for: Cholangiocarcinoma Primary Sclerosing Cholangitis (PSC):
Histology of PSC ,[object Object],[object Object],[object Object],[object Object]
Histology of PSC ,[object Object],[object Object],[object Object],[object Object],> Looks like Ulcerative Colitis! Histology of PSC
 
 
 
 
Histology of PSC ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],> Looks like Ulcerative Colitis! Histology of PSC
 
 
 
 
 
 
 
 
Tombstone Scar
Tombstone Scars
Tombstone Scars
Histology of PSC ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],> Looks like Ulcerative Colitis! ,[object Object],[object Object],[object Object],[object Object],Histology of PSC
In situ High Grade Dysplasia
In situ papillary cholangiocarcinoma
Cholangiocarcinoma
 
 
Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma Sjogren’s   10-30 Male Ulcerative Colitis Crohn’s Disease
Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma,  Sjogren’s  10-30 Male Ulcerative Colitis Crohn’s Disease
Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma,  Sjogren’s  10-30 Male Ulcerative Colitis Crohn’s Disease
Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx Ducts Affected 40-60 Female RA, CREST Scleroderma,  Sjogren’s  Small to medium 10-30 Male Ulcerative Colitis Crohn’s Disease All ducts
Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx Ducts Affected Method of Dx 40-60 Female RA, CREST Scleroderma,  Sjogren’s  Small to medium Biopsy 10-30 Male Ulcerative Colitis Crohn’s Disease All ducts MRCP/ERCP
vs. P S C  S  UC KS P B C  B UCKS NOT Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) MNEMONIC!!!
vs. P S C  S  UC KS P B C  B UCKS NOT Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) MNEMONIC!!!

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Autoimmune Liver Disease - Kuwait

  • 1. Autoimmune Liver Diseases: AIH, PBC, PSC Neil Theise, MD Depts. of Pathology and Medicine (Digestive Diseases) Beth Israel Medical Center – Albert Einstein College of Medicine New York City
  • 3. Gender: Mostly female Autoimmune Hepatitis:
  • 4. Gender: Mostly female Age: 40’s - 60’s Autoimmune Hepatitis:
  • 5. Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Autoimmune Hepatitis:
  • 6. Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Presentation: Very severe activity &/or very late stage Autoimmune Hepatitis:
  • 7. Dynamics of Activity and Progression of Autoimmune Hepatitis over Time Assessment is NOT like chronic viral hepatitis!
  • 8. Stage of Disease Time Viral hepatitis: Progression vs. activity over time
  • 9. Stage of Disease Time Autoimmune hepatitis: Progression vs. activity over time
  • 10. Stage of Disease Biopsy: Advanced disease, but mild or “burned out hepatitis” Autoimmune hepatitis: Progression vs. activity over time
  • 11. Biopsy: Advancing disease and severe activity Stage of Disease Autoimmune hepatitis: Progression vs. activity over time
  • 12. Biopsy: Little scarring, but severe activity Stage of Disease Autoimmune hepatitis: Progression vs. activity over time
  • 13. Stage of Disease Time Autoimmune hepatitis: Progression vs. activity over time No biopsy is likely to show: mild activity and little scarring…
  • 14. Gender: Mostly female Age: 40’s - 60’s Autoantibodies: anti-nuclear (ANA) anti-smooth muscle (ASMA) anti-mitochondrial (AMA) anti-liver kidney microsomal 1 (LKM1) Presentation: Very severe activity &/or very late stage Treatment: Immune suppression, transplant for endstage. Autoimmune Hepatitis:
  • 17. Gender: Women Primary Biliary Cirrhosis (PBC):
  • 18. Gender: Women Age: Middle aged to older Primary Biliary Cirrhosis (PBC):
  • 19. Gender: Women Age: Middle aged to older Associated diseases: Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Primary Biliary Cirrhosis (PBC):
  • 20. Gender: Women Age: Middle aged to older Associated diseases: Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Serologic markers: AMA (ASMA, ANA) Primary Biliary Cirrhosis (PBC):
  • 21. Gender: Women Age: Middle aged to older Associated diseases: Scleroderma Hashimoto’s thyroiditis CREST syndrome Sjogren’s syndrome, etc…. Serologic markers: AMA (ASMA, ANA) Bile ducts involved: Medium to small ducts ONLY Primary Biliary Cirrhosis (PBC):
  • 22. PBC, Stage 1: Bile duct injury/loss
  • 23.  
  • 24.  
  • 25.  
  • 26. PBC, Stage 2: Ductular reaction
  • 27.  
  • 28.  
  • 29. PBC, Stage 3: Fibrosis From portal fibrosis to Transition to cirrhosis…
  • 30. PBC, Stage 4: Cirrhosis
  • 31.
  • 32.  
  • 33.  
  • 36. PBC AIH “ Overlap” Hepatitis
  • 37. PBC AIH “ Overlap” Syndrome
  • 39. Gender: Men Primary Sclerosing Cholangitis (PSC):
  • 40. Gender: Men Age: Teens to 30’s Primary Sclerosing Cholangitis (PSC):
  • 41. Gender: Men Age: Teens to 30’s Associated diseases: Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Primary Sclerosing Cholangitis (PSC):
  • 42. Gender: Men Age: Teens to 30’s Associated diseases: Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Primary Sclerosing Cholangitis (PSC):
  • 43. Gender: Men Age: Teens to 30’s Associated diseases: Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Ducts involved: Large extrahepatic to small intrahepatic Primary Sclerosing Cholangitis (PSC):
  • 44. Gender: Men Age: Teens to 30’s Associated diseases: Inflammatory bowel disease ( U.C. or Crohn’s) 70% have IBD 70% of IBD will develop PSC Serologic markers: ANCA…? Ducts involved: Large extrahepatic to small intrahepatic At increased risk for: Cholangiocarcinoma Primary Sclerosing Cholangitis (PSC):
  • 45.
  • 46.
  • 47.  
  • 48.  
  • 49.  
  • 50.  
  • 51.
  • 52.  
  • 53.  
  • 54.  
  • 55.  
  • 56.  
  • 57.  
  • 58.  
  • 59.  
  • 63.
  • 64. In situ High Grade Dysplasia
  • 65. In situ papillary cholangiocarcinoma
  • 67.  
  • 68.  
  • 69. Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma Sjogren’s 10-30 Male Ulcerative Colitis Crohn’s Disease
  • 70. Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma, Sjogren’s 10-30 Male Ulcerative Colitis Crohn’s Disease
  • 71. Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx 40-60 Female RA, CREST Scleroderma, Sjogren’s 10-30 Male Ulcerative Colitis Crohn’s Disease
  • 72. Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx Ducts Affected 40-60 Female RA, CREST Scleroderma, Sjogren’s Small to medium 10-30 Male Ulcerative Colitis Crohn’s Disease All ducts
  • 73. Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) vs. Age Gender Assoc’d Dx Ducts Affected Method of Dx 40-60 Female RA, CREST Scleroderma, Sjogren’s Small to medium Biopsy 10-30 Male Ulcerative Colitis Crohn’s Disease All ducts MRCP/ERCP
  • 74. vs. P S C S UC KS P B C B UCKS NOT Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) MNEMONIC!!!
  • 75. vs. P S C S UC KS P B C B UCKS NOT Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC) MNEMONIC!!!

Notas do Editor

  1. Fig. 16.1A. Variation in the severity of fibrosis in chronic biliary disease. These two slides are taken from a single block of liver obtained at transplantation from a patient with primary biliary cirrhosis. One area shows established cirrhosis (A). In an adjacent area there is preservation of normal vascular relationships with no evidence of fibrosis (B). (P = portal tract, H = hepatic venule). H&E.
  2. Fig. 16.1B. Variation in the severity of fibrosis in chronic biliary disease. These two slides are taken from a single block of liver obtained at transplantation from a patient with primary biliary cirrhosis. One area shows established cirrhosis (A). In an adjacent area there is preservation of normal vascular relationships with no evidence of fibrosis (B). (P = portal tract, H = hepatic venule). H&E.
  3. Fig. 12.7B. Metaplasia of gallbladder mucosa in chronic cholecystitis. (A) A lobule of pyloric glands is seen in the lamina propria. The surface epithelium is of gastric foveolar type. (B) Intestinal metaplasia with columnar and goblet cells; endocrine cells were identified by immunohistochemistry. H&E.
  4. Fig. 11.8B. (A) Suppurative cholangitis with cholangitic abscess (*) and remnants of the bile-duct epithelium (arrow) in a case of bacterial cholangitis. (B) Non-suppurative cholangitis showing epithelial damage (arrow) and periductal infiltration of lymphocytes and plasma cells in primary biliary cirrhosis. H & E.
  5. Fig. 11.7B. Biliary epithelial dysplasia associated with hepatolithiasis. (A) Lining epithelium of a large intrahepatic bile duct shows micropapillary hyperplasia with cellular dysplasia. H & E. (B) Close-up of micropapillary hyperplasia with mild dysplasia illustrating nuclear pseudostratification. H & E.
  6. Fig. 15.62. Intrahepatic cholangiocarcinoma. This peripheral tumour has replaced the entire left lobe.
  7. Fig. 15.63. Intrahepatic cholangiocarcinoma. This lobectomy specimen contains a hard, yellow-white tumour that arose near the hilum and spread peripherally.
  8. Fig. 15.65. Cholangiocarcinoma. Poorly formed glands with frequent mitoses. H&E.