This document discusses different types of autoimmune cholangiopathies: primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). PBC involves destruction of small and medium bile ducts by lymphocytes and plasma cells, leading to cirrhosis over years. It affects middle-aged women and is associated with antimitochondrial antibodies. PSC involves inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts, often in patients with inflammatory bowel disease. It is characterized by "onion skin" fibrosis and strictures seen on MRI. Both can progress to liver failure but PSC has a higher risk of cholangiocarcinoma. Secondary biliary

1. AUTOIMMUNE CHOLANGIOPATHIES

2. Learning Objectives
Enlist types of autoimmune Cholangiopathies.
Describe primary biliary cholangitis, its pathogenesis,
morphology and clinical manifestations.
Describe primary sclerosing cholangitis, its pathogenesis,
morphology and clinical manifestations.
Compare the morphology of primary biliary cholangitis with
primary sclerosing cholangitis.
What is secondary biliary cirrhosis enlist its causes.

3. Autoimmune Cholangiopathies
Immunologically mediated disorders that involve intrahepatic
bile ducts; it is of two types:
I- Primary biliary cholangitis (PBC)
II- Primary sclerosing cholangitis (PSC)

4. Primary Biliary Cholangitis (PBC)
An autoimmune disease whose primary feature is non-suppurative
inflammatory destruction of small and medium sized intrahepatic bile
ducts
Large intrahepatic ducts and extra hepatic biliary tree not involved
Middle age women (40-50years), F:M ratio = 6:1
Environmental and genetic factors involved in pathogenesis

5. PBC
Pathogenesis
Autoimmune disorder
Anti-mitochondrial antibodies are the most characteristic finding
T cells specific for certain mitochondrial enzymes; another feature of
the disease
Aberrant expression of MHC class II molecules on bile duct epithelial
cells
Accumulation of autoreactive T cells around bile ducts and frequent
presences of other autoantibodies against nuclear pore proteins and
other cellular components

6. PBC
Morphology
Interlobular bile ducts are actively destroyed by lymphoplasmacytic
inflammation with or without granulomas (the florid duct lesion)
Patchy distribution; common to see a single bile duct under immune
attack in one level of biopsy sparing near by ducts
Ductular reaction and duct injury later leads to development of portal-
portal septal fibrosis
Un treated cases leads to end-stage liver disease in years or
decades mostly due to development cirrhosis or portal hypertension
in some cases

7. PBC
Portal tract markedly expanded by
infiltrate of lymphocytes and plasma
cells
Granulomatous reaction against bile
duct destruction (florid duct lesion)
Periportal cholestasis

8. PBC
Clinical Course
Most patients are diagnosed while asymptomatic through discovery of
an elevated serum alkaline phosphatase level or severe itching
Hypercholesterolemia is common
Anti-mitochondrial antibodies present in 90-95% of patients highly
characteristic of the lesion
Confirmed by liver biopsy showing florid duct lesion
Associated extrahepatic conditions include; Sjögren syndrome,
scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon
and celiac disease

9. Primary Sclerosing Cholangitis (PSC)
Chronic cholestatic disorder, characterized by inflammation
and obliterative progressive fibrosis and destruction of extra
and intrahepatic bile ducts
Occur in the 3rd through 5th decades of life, most often after
development of IBD, particularly UC which coexists in approx.
70% of affected patients Conversely, the prevalence of PSC
among persons with UC is about 4%.

10. PSC
Pathogenesis
Cause unknown, several features of PSC suggest
immunologically mediated injury to bile ducts, T cells in the
periductal stroma, presence of autoantibodies an association
with HLA-B8 and other MHC alleles and clinical linkage to
ulcerative colitis all support an underlying immunologic process.
Autoantibody profile in PSC is not characteristic as in PBC but
antinuclear cytoplasmic antibodies (p-ANCA) found in 80% of
the cases

11. PSC
Morphology
Larger ducts shows chronic inflammation with superimposed acute inflammation with narrowing of lumen
either because edema and inflammation or subsequent scarring
Smaller ducts show a striking circumferential fibrosis (onion skinning) around an increasingly atrophic
duct lumen leaving behind a dense button of scar tissue, the virtually diagnostic tombstone scar
One can miss histological features in needle biopsy thus diagnosis depends MRI which shows beading of
intra and extrahepatic biliary tree due to irregular biliary strictures and dilations
In response to duct loss, bile ductular proliferation, portal-portal septal fibrosis, cirrhosis follows, imparting
green color to the liver
Biliary intraepithelial neoplasia may appear, a precursor of cholangiocarcinoma

12. PSC

13. PSC
Clinical Course
Asymptomatic patients may come to attention due to persistently elevated
levels of serum alkaline phosphatase.
Other present symptoms related to acute cholangitis such as; fever, right
upper quadrant tenderness, and sometimes acute jaundice
Patients who present at later stages may have progressive fatigue, pruritus,
and chronic jaundice.
PSC generally has a protracted course over many years.
Cholangiocarcinoma develops in 10% to 15% of patients with PSC, with a
median time from diagnosis to malignant transformation of 5 years

15. Secondary Biliary Cirrhosis (SBC)
Etiology: Extra hepatic bile duct obstruction, biliary atresia,
gallstones, strictures, or carcinoma of pancreatic head
Pathologic Findings: Prominent bile stasis in bile ducts, bile
ductular proliferation, portal tract edema, neutrophils infiltrate,
necrosis, fibrosis leads to cirrhosis

16. References
Basic Pathology, 10th Edition Kumar, Abbas, Aster Chapter 16
Liver and Gallbladder Pages 663-66.
www.webPathology.com.