Primary Biliary Cirrhosis

Clinical Description:

 Disease in which bile ducts in liver is slowly destroyed

 Destruction of bile ducts causes harmful substances to build up in liver
 Causes inflammation and scarring that destroy ducts in liver slowing or blocking the normal flow
of bile
 Bile is produced in the liver -> travels through bile ducts -> gallbladder -> small intestine
 It helps in the digestion of fats and fat-soluble vitamins (A, D, E & K)
 Damaged bile ducts cause inflammation -> bile builds up in liver -> liver tissue gets injured
(CIRRHOSIS)
 Scar tissue replaces healthy liver tissue -> blocks blood flow through liver
 Cause of the disease is still unclear
 Many experts believe that PBC is an autoimmune disease -> body turns against own cells
 May also be caused by genetic, environmental or immunologic factors
 T – cell mediated destruction -> activated CD4 and CD8 lymphocytes -> clogging of bile ducts ->
degeneration of hepatocytes and fibrosis
 Autoimmune nature -> infiltration of liver with macrophages and lymphocytes -> intense
inflammatory response

Why Autoimmune?

 Abnormalities of humeral and cellular immune systems

 Multiple circulating antibodies
 Granulomas in liver and regional lymph nodes
 Impaired regulation of both B and T lymphocytes
 Association with variety of autoimmune-mediated diseases

Risk Factors:

 Sex
- 90% are women
- Immune system disorders affect more women
 Age
- Onset occurs between 35 to 60 years old
- Older adults can develop the disease
 Race
- Common in Northern Europeans
 Family History
- Is not hereditary
- Family member with the disease increases the risk
 Environmental
- Viral infections
- Bacterial infections
- Chemicals
Clinical Manifestations:

Early Stage

 Fatigue
- Energy levels normal in the morning
- Falls later in the day
- Don’t improve with rest
 Pruritis (Itching)
- Bothersome over legs, arms and back.
- Worse at night
- Disturb sleep -> fatigue worsens -> lead to depression
 Sicca Syndrome (Dryness of eyes and mouth)
- Often occurs in people with autoimmune disorders
- Inflammation in moisture-secreting glands
- Decreased production of tears and saliva

Later Stage

 Jaundice
- Common sign of liver disease
- Turns skin and whites of eyes yellow
- Due to high bilirubin level
- Bilirubin begins to build up in blood and manifest in skin and eyes
 Hyperpigmentation
- Inadequate flow of bile increase production of melanin
- Cause skin to become darker
 Edema (Swollen feet) and Ascites (Swollen abdomen)
- Liver damage progress
- Body begins to retain salt and fluids
- Water accumulates in feet and ankles
- In time, fluid also collect in abdomen
 Xanthomas (Cholesterol deposits)
- Bile eliminates excess cholesterol
- Cholesterol in the blood increases
- Formation of fatty deposits in skin around eyes, eyelids, creases in palms, soles, elbows,
knees or buttocks
- Don’t appear until blood cholesterol reaches very high levels
 Digestive Problems
- Cause intestinal problems
- Diarrhea
- Steatorrhea
- Greasy, bad smelling stools -> poor fat digestion
 Urinary Tract Infection
- Women with PBC experiences reccuring UTI
- Bacteria responsible for UTI may play a role in PBC
Diagnostic Approach:

 Liver Biochemical Tests

- Blood test checking levels of enzymes that may indicate liver disease and bile duct injury
- Alkaline phosphatase is elevated in most people with PBC
- Changes in biochemical tests are related in part to the stage of disease and severity of
histologic lesions

 Autoantibodies
- Antibodies are proteins in blood that help destroy bacteria and harmful pathogens
- Most people with PBC have anti-mitochondria antibodies (AMA)
- AMA is an antibody that target enzymes in the mitochondria
 Histology
- Confirm the presence or absence of disease
- Small sample of liver is removed and examined
- Used to confirm and determine extent of disease
 Imaging Studies
- Ultrasound Imaging
o Noninvasive test using high-frequency sound waves
o Create precise images of structures within the body
o Used to rule out other causes of bile flow blockage (e.g. gallstones or tumors)
- Magnetic Resonance Elestography (MRE)
o Combined magnetic resonance imaging (MRI) with low-frequency sound waves
o Create clear and detailed cross-sectional images of the body
o Low-frequency sound waves help reveal physical properties of tissues and organs
- Endoscopic Retrograde Cholangiopancreatography (ERCP)
o Used to detect any abnormalities in bile ducts
o Uses flexible telescope-like instrument to take x-ray pictures of the bile ducts and
pancreas

Characteristic Laboratory Findings:

 Elevated alkaline phosphatase (ALP)

 Elevated γ-glutamyl transpeptidase (GGT)
 Slight increase of transaminases (AST and ALT)
 Significant increase in IgM
 Lipid levels and cholesterol levels may be increased
 Increased high-density lipoprotein (HDL) fraction
 Increased erythrocyte sedimentation rate (ESR)
 Evidence of anti-mitochondrial antibodies (AMA)

As the disease progresses

 Elevated bilirubin level

 Prolonged prothrombin time
 Decreased albumin level
Stages of PBC:

 Stage 1 (Portal Stage of Ludwig)

- Portal inflammation
- Bile duct abnormalities
- Can both be present
 Stage 2 (Periportal Stage)
- Perportal fibrosis is present
- Periportal inflammation
- Prominent enlargement of portal tracts
 Stage 3 (Septal Stage)
- Septal fibrosis
- Active inflammatory
- Passive paucicellular septa
- Can both be present
 Stage 4 (Cirrhosis)
- Nodules with various degrees of inflammation

Clinical Complications:

 Cirrhosis
- Interferes with the liver’s ability to carry out essential functions
- Lead to liver failure
- Late stage of PBC
 Portal Hypertension
- Where blood from intestine, spleen and pancreas enter liver
- Increased pressure in portal vein
- Scar tissue block normal circulation -> blood backs up -> hormones, drugs and toxins are not
filtered properly before entering bloodstream
 Varices (Enlarged veins)
- Blood back up to veins -> stomach and esophagus -> because of vein’s thin walls ->
increased pressure -> bleeding
 Liver Cancer
- Cirrhosis -> hepatocellular carcinoma
- Affects hepatocytes
 Osteoperosis
- Liver scarring interferes with ability of liver to process vitamin D and calcium
 Vitamin Deficiencies
- Lack of bile affects absorption of fats and fat-soluble vitamins

Diseases Resembling PBC:

 Autoimmune Hepatitis (AIH)

- Body’s immune system attacks liver cells
- Self-perpetuating hepatocellular inflammation
- Termed Overlap Syndrome
- Typically chronic
 - Can lead to cirrhosis
 Primary Sclerosing Cholangitis (PSC)
- Damages and blocks bile ducts from inside and outside the liver
- Characterized by chronic inflammation and fibrosis of bile ducts
- Linked to inflammatory bowel disease

Criteria PBC AIH PSC

Clinical Manifestations Fatigue Same with PBC Same with PBC
Pruritus Enlarged liver Inflammatory bowel
Sicca syndrome disease
Incidence Middle aged females Females (70%) Males (80%)
(90%) Children and adolescent Children

Autoantibodies Anti-mitochondrial Anti-smooth muscle Negative

antibodies (AMA) antibodies (SMA)
Antinuclear antibodies
(ANA)
Anti -liver and kidney
microsomes (A-LKM)
Serum ALP Elevated Elevated
Serum ALT and AST Slightly increased Elevated Elevated
Serum GGT Elevated Elevated

Treatment:

 Ursodeoxycholic Acid (UDCA)

- Used to treat gallstones
- Affects body’s bile acids and reduce inflammation
- Not a cure
 Liver Transplant
- Last resource
- When liver begins to fail
- May help prolong life