AUTOIMMUNE

HEPATOBILIARY DISEASES

By FADHILI MWIVALI
MS/00081/017
 OUTLINE

1. Autoimmune hepatitis
2. Primary biliary Cholangitis(PBC)
3. Primary Sclerosing Cholangitis(PSC)

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 OBJECTIVES

1. Describe autoimmune hepatitis , its pathogenesis, morphology and

clinical manifestations
2. Describe primary biliary cholangitis, its pathogenesis, morphology and
clinical manifestations
3. Describe primary sclerosing cholangitis, its pathogenesis, , morphology
and clinical manifestations
4. Enlist types of Cholangiopathies
5. Compare the morphology of primary biliary cholangitis with primary
sclerosing cholangitis

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 AUTOIMMUNE HEPATITIS
▪ Chronic hepatitis of unknown etiology • CMI attack is directed against the hepatocytes
▪ A.k.a Lupoid hepatitis OR chronic • CD4 T lymphocytes are capable of being
aggressive hepatitis sensitized to hepatocyte membrane and
destroying liver cells
Pathogenesis • Humoral immunity plays a role in extra-hepatic
• Exact pathogenesis is unknown manifestations of arthritis, vasculitis and
• Genetic predisposed individuals with glomerulonephritis by Immune complex
exposure to environmental agent triggers deposition and complement activation
the autoimmune pathogenic process
• Genetic predisposing factors
1.HLA-DR3- early onset ,severe
2. HLA-DR4- late onset, Better
prognosis

• Environmental triggers:
Infections(HAV,HBV,EBV), Drugs (NSAIDs,
statins)

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 CLASSIFICATION

Two types of AIH

Based on serological markers

❖Type 1-
• more common in middle-age and older Individuals
• Antinuclear (ANA), anti–smooth muscle actin (SMA), antimitochondrial
(AMA), and anti–soluble liver antigen/ liver-pancreas antigen (anti-SLA/LP)
antibodies
❖Type 2
• usually seen in children and teenagers
• Anti–liver kidney microsome-1 antibodies and anti–liver cytosol-1 antibodies

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✓ Clinical Features
LAB FEATURES
• Symptoms
Elevated AST, ALP
1. Fatigue
Hypergammaglobulinemia
2. Jaundice
Hyperbilirubinemia
3. Pruritis
Diagnosis
4. Anorexia
1.Serology
5. Cushingoid features
Anti-smooth muscle Actin (SMA) or anti-
6. Fever
LKM 1
• Signs Atypical p-ANCA
1. Hepatosplenomegaly 2. Biopsy
2. Spider Naevi Management
3. Jaundice Immunosuppressants- Azathioprine,
4. Ascites Steroids
5. Encephalopathy

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 Source:Hutchinsons Clinical Methods 23Ed

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 PRIMARY SCLEROSING CHOLANGITIS

 Autoimmune disorder of unknown cause

 Combination of environmental factors &
genetic predisposition
 Primary feature is non-suppurative
inflammatory destruction of small and
intrahepatic and extrahepatic bile ducts
 The ducts become strictured and fibrotic
causing obstruction
 Buildup of back pressure by bile causing
hepatitis, fibrosis and cirrhosis

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 CLINICAL PRESENTATION

Presentation Diagnosis
1. Pruritis 1.Liver function tests
2. Fatigue “Cholestatic picture”- Bile stasis
3. Jaundice 1. Hyperbilirubinemia
4. RUQ pain 2. Elevated ALP & GGT
5. Hepatomegaly 3. Elevated ALT and AST ( Hepatitis)
Risk Factors 2.Autoantibodies –ANCA, ANA, Anticardiolipin antibodies
1.Family history Not specific to PSC
2.Age 30-40 3.MRCP- Magnetic Resonance Cholangiopancreatography-
3.Male predilection Gold standard. MRI scan of liver, bile ducts and pancreas-
4. Ulcerative colitis shows bile duct lesions and strictures
4. Biopsy
“Onion-skin appearance”

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 Robin’s Basic Pathology 10e

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 COMPLICATIONS & MANAGEMENT
➢ Complications
1. Acute bacterial Cholangitis
2. Cholangiocarcinoma
3. Colorectal cancer
4. Cirrhosis and liver failure
5. Biliary strictures
6. Deficient fat soluble vitamins

➢ Management
1. Liver transplant
2. ERCP
3. Ursodeoxycholic acid- Slow progression
4. Cholestyramine- Bile acid sequestrant-(Pruritis)
5. Monitor for complications-
Cholangiocarcinoma, Cirrhosis

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 PRIMARY BILIARY CHOLANGITIS
Autoimmune disorder whose primary feature is Lab features
non-suppurative inflammatory destruction of 1. Hypercholesterolemia
small and medium sized intrahepatic ducts 2. Liver function tests- Bilirubin, ALP
Large intrahepatic ducts and extra-biliary tree 3. Autoantibodies- Antimitochondrial
NOT involved antibodies
F:M 6:1 4. Liver biopsy
➢ Pathogenesis
▪ Autoimmune disorder Associated extrahepatic conditions
▪ Environmental and genetic factors involved 1. Sjogren syndrome
▪ T cells specific for anti-mitochondrial 2. Scleroderma
enzymes 3. Rheumatoid Arthritis
▪ Aberrant expression of MHC II molecules on 4. Raynaud phenomenon
bile duct epithelial cells 5. Celiac disease
▪ Accumulation of autoreactive T cells around
bile ducts and autoantibodies against Management
nuclear core proteins Ursodeoxycholic acid
➢ Clinical Features
Similar to PSC
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 MORPHOLOGY
• Florid duct lesion- Interlobular ducts are actively destroyed by
lymphoplasmacytic inflammation with or without granulomas
• Ductopenia- loss of bile ducts

A
Robin’s Basic Pathology 9 e
Autoimmune Hepatobiliary Diseases
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Feature PBC PSC
Age Mean age is 50 years Mean age is 30 years

Gender predilection Female Male

Clinical course Progressive Unpredictable but progressive

Associated conditions Sjogren syndrome Pancreatitis

Scleroderma Inflammatory Bowel Disease
Thyroid disease Idiopathic fibrosing disease

Radiology Normal Strictures and beading of large bile

ducts
Duct lesions Florid Duct lesions and Inflammatory destruction of
loss of small ducts only extrahepatic and large intrahepatic
ducts

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REFERENCES

1.Robbins Basic Pathology, 10e

2.Pathologyoutlines.com

3. Ncbi.com

4. Hutchinsons Clinical Methods_23Ed

THE END

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