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!!!