Post on 07-May-2015
Autoimmune Liver Diseases:AIH, PBC, PSC
Neil Theise, MDDepts. of Pathology and Medicine (Digestive Diseases)
Beth Israel Medical Center – Albert Einstein College of MedicineNew York City
Autoimmune Hepatitis:
Gender: Mostly femaleAutoimmune Hepatitis:
Gender: Mostly femaleAge: 40’s - 60’s
Autoimmune Hepatitis:
Gender: Mostly femaleAge: 40’s - 60’sAutoantibodies: anti-nuclear (ANA)
anti-smooth muscle (ASMA)anti-mitochondrial (AMA)anti-liver kidney microsomal 1 (LKM1)
Autoimmune Hepatitis:
Gender: Mostly femaleAge: 40’s - 60’sAutoantibodies: 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!
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Viral hepatitis: Progression vs. activity over time
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Autoimmune hepatitis: Progression vs. activity over time
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Biopsy: Advanced disease, but mild or “burned out hepatitis”
Autoimmune hepatitis: Progression vs. activity over time
Biopsy: Advancing disease and severe activity
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Biopsy: Little scarring, but severe activity
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Autoimmune hepatitis: Progression vs. activity over time
No biopsy is likely to show:mild activity and little scarring…
Gender: Mostly femaleAge: 40’s - 60’sAutoantibodies: anti-nuclear (ANA)
anti-smooth muscle (ASMA)anti-mitochondrial (AMA)anti-liver kidney microsomal 1 (LKM1)
Presentation: Very severe activity &/or very late stageTreatment: Immune suppression, transplant for endstage.
Autoimmune Hepatitis:
Autoimmune Hepatitis: plasma cells
Perivenular confluent necrosis
Gender: Women
Primary Biliary Cirrhosis (PBC):
Gender: WomenAge: Middle aged to older
Primary Biliary Cirrhosis (PBC):
Gender: WomenAge: Middle aged to olderAssociated diseases: Scleroderma
Hashimoto’s thyroiditisCREST syndromeSjogren’s syndrome, etc….
Primary Biliary Cirrhosis (PBC):
Gender: WomenAge: Middle aged to olderAssociated diseases: Scleroderma
Hashimoto’s thyroiditisCREST syndromeSjogren’s syndrome, etc….
Serologic markers: AMA (ASMA, ANA)
Primary Biliary Cirrhosis (PBC):
Gender: WomenAge: Middle aged to olderAssociated diseases: Scleroderma
Hashimoto’s thyroiditisCREST syndromeSjogren’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 toTransition to cirrhosis…
PBC, Stage 4:Cirrhosis
PBC, Endstage:Clinically, most often:
- Severe cholestatic diseaseor
-Portal hypertension (ascites, varisces, etc.)
Livers are usually not fully cirrhotic!…stage 3 to 4…
PBC AIH
PBC AIH
PBC AIH
“Overlap” Hepatitis
PBC AIH
“Overlap” Syndrome
PBC
AIH
NRH
Gender: Men
Primary Sclerosing Cholangitis (PSC):
Gender: MenAge: Teens to 30’s
Primary Sclerosing Cholangitis (PSC):
Gender: MenAge: Teens to 30’sAssociated diseases: Inflammatory bowel disease
(U.C. or Crohn’s)70% have IBD70% of IBD will develop PSC
Primary Sclerosing Cholangitis (PSC):
Gender: MenAge: Teens to 30’sAssociated diseases: Inflammatory bowel disease
(U.C. or Crohn’s)70% have IBD70% of IBD will develop PSC
Serologic markers: ANCA…?
Primary Sclerosing Cholangitis (PSC):
Gender: MenAge: Teens to 30’sAssociated diseases: Inflammatory bowel disease
(U.C. or Crohn’s)70% have IBD70% of IBD will develop PSC
Serologic markers: ANCA…?Ducts involved: Large extrahepatic to small intrahepatic
Primary Sclerosing Cholangitis (PSC):
Gender: MenAge: Teens to 30’sAssociated diseases: Inflammatory bowel disease
(U.C. or Crohn’s)70% have IBD70% of IBD will develop PSC
Serologic markers: ANCA…?Ducts involved: Large extrahepatic to small intrahepaticAt increased risk for: Cholangiocarcinoma
Primary Sclerosing Cholangitis (PSC):
Histology of PSC
Extrahepatic pancreato-biliary duct changes • Chronic inflammation• Focal ulceration• Strictures: inflammation/edema >>> scar
Histology of PSC
Extrahepatic pancreato-biliary duct changes • Chronic inflammation• Focal ulceration• Strictures: inflammation/edema >>> scar>Looks like Ulcerative Colitis!
Histology of PSC
Histology of PSC
Extrahepatic pancreato-biliary duct changes • Chronic inflammation• Focal ulceration• Strictures: inflammation/edema >>> scar
Intrahepatic bile duct changes • Atrophy• Circumferential, “onion skin” fibrosis• “Tombstone scars”• +/- mild mononuclear portal infiltrates
>Looks like Ulcerative Colitis!
Histology of PSC
Tombstone Scar
Tombstone Scars
Tombstone Scars
Histology of PSC
Extrahepatic pancreato-biliary duct changes • Chronic inflammation• Focal ulceration• Strictures: inflammation/edema >>> scar
Intrahepatic bile duct changes • Atrophy• Circumferential, “onion skin” fibrosis• “Tombstone scars”• +/- mild mononuclear portal infiltrates
>Looks like Ulcerative Colitis!
Biliary neoplasia • Progressive dysplasia• Severe dysplasia = carcinoma in situ• Cholangiocarcinoma
Histology of PSC
In situ High Grade Dysplasia
In situ papillary cholangiocarcinoma
Cholangiocarcinoma
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)vs.
Age
Gender
Assoc’d Dx
40-60
Female
RA, CRESTScleroderma
Sjogren’s
10-30
Male
Ulcerative ColitisCrohn’s Disease
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)vs.
Age
Gender
Assoc’d Dx
40-60
Female
RA, CRESTScleroderma,
Sjogren’s
10-30
Male
Ulcerative ColitisCrohn’s Disease
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)vs.
Age
Gender
Assoc’d Dx
40-60
Female
RA, CRESTScleroderma,
Sjogren’s
10-30
Male
Ulcerative ColitisCrohn’s Disease
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)vs.
Age
Gender
Assoc’d Dx
Ducts Affected
40-60
Female
RA, CRESTScleroderma,
Sjogren’s
Small to medium
10-30
Male
Ulcerative ColitisCrohn’s Disease
All ducts
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)vs.
Age
Gender
Assoc’d Dx
Ducts Affected
Method of Dx
40-60
Female
RA, CRESTScleroderma,
Sjogren’s
Small to medium
Biopsy
10-30
Male
Ulcerative ColitisCrohn’s Disease
All ducts
MRCP/ERCP
vs.
PSC S UC KS
PBC BUCKSNOT
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)
MNEMONIC!!!
vs.
PSC S UC KS
PBC BUCKSNOT
PrimaryBiliary
Cirrhosis(PBC)
PrimarySclerosingCholangitis
(PSC)
MNEMONIC!!!