Chapter 18 –Intrahepatic Biliary Tract Disease: PRIMARY BILIARY CIRRHOSIS (PBC) Flashcards
What is PBC?
- inflammatory autoimmune disease mainly affecting the intrahepatic bile ducts.
- The primary feature of this disease is a nonsuppurative, inflammatory destruction of medium-sized intrahepatic bile ducts.
- It is accompanied by portal inflammation, scarring, and eventual development of cirrhosis and liver failure. [54]
Why is PBC. the disease name is somwehat misleading for patients diagnosed early at a pre-cirrhotic stage?
Because cirrhosis develops only after many years PBC
PBC is primarily a disease of what age?
middle-aged women, with a female predominance over males in excess of 6 : 1.
It may occur between the ages of 20 and 80 years, with peak incidence between 40 and 50 years of age.
What is the epidemiology of
PBC?
The incidence of this disease in the United States is approximately 27 per million people (7 and 45 per million in males and females, respectively).
Both the incidence
and prevalence of PBC are increasing and geographic clustering has been reported, suggesting that genetic and environmental factors are important in the pathogenesis of the disease.
Family members of PBC patients have an increased risk of developing the disease.
What is the clinical course of PBC?
The onset is insidious, usually presenting with fatigue and pruritus.
Hepatomegaly is a typical finding, and eyelid xanthelasmas arise as a result of infiltration of the nasal area of the eyelid by
cholesterol-rich macrophages.
Hyperpigmentation due to melanin deposition and an
inflammatory arthropathy are seen in 25% to 40% of cases.
Signs and symptoms of chronic
liver disease, such as spider nevi, are late features.
Over a period of two or more decades,
patients develop cirrhosis and complications that include portal hypertension with variceal
bleeding, and hepatic encephalopathy.
What are the laboratory findings in PBC?
- Serum alkaline phosphatase and cholesterol are almost always elevated ,even at onset;
- hyperbilirubinemia is a late development and usually signifies incipient hepatic decompensation.
- Antimitochondrial antibodies are present in 90% to 95% of patients. They are highly characteristic of PBC and an essential element for diagnosis, together with the elevation of alkaline phosphatase and γ-glutamyltransferase, which are markers of cholestasis.
What are highly characteristic of PBC and an essential element for diagnosis?
Antimitochondrial antibodies are present in 90% to 95% of patients.
together with the elevation of alkaline phosphatase and γ-glutamyltransferase, which are markers of cholestasis.
What is the pathogenesis of PBC?
PBC is thought to be an autoimmune disorder, but its pathogenesis is still unknown.
Many potential mechanisms have been proposed, including aberrant expression of MHC class II
molecules on bile duct epithelial cells, accumulation of autoreactive T cells around bile ducts,
reaction of antimitochondrial antibodies to hepatocytes, or of other antibodies against cellular
components (nuclear pore proteins, and centromeric proteins, among others). [55]
The antimitochondrial antibodies, the characteristic autoantibodies in PBC, target the E2 component
of the pyrurate dehydrogenase complex (PDC-E2). PDC-E2–specific T cellsare also present in these patients,supporting the notion of immune-mediated pathogenesis
What is the morphology of PBC?
PBC is the prototype of conditions leading to small-duct biliary fibrosis and cirrhosis.
PBC is a focal and variable disease, showing different degrees of severity in different portions of the liver.
During the pre-cirrhotic stage portal tracts are infiltrated by a dense accumulation of lymphocytes, macrophages, plasma cells, and occasional
eosinophils.
Interlobular bile ducts are infiltrated by lymphocytes and may show noncaseating granulomatous inflammation ( Fig. 18-31 ) and undergo progressive
destruction.
With time the obstruction to intrahepatic bile flow leads to progressive secondary hepatic damage.
Portal tracts upstream from damaged bile ducts show bile ductular proliferation, inflammation, and necrosis of the adjacent periportal hepatic parenchyma. The
parenchyma develops generalized cholestasis.
Over years to decades, relentless portal tract
scarring and bridging fibrosis lead to cirrhosis.
What is the appearance of PBC macroscopically?
Macroscopically, the liver does not at first appear abnormal, but as the disease progresses
bile stasis stains the liver green.
The capsule remains smooth and glistening until a fine
granularity appears, representing deposition of fibrous septa.
This process culminates in a
well-developed, uniform micronodular cirrhosis.
Liver weight is at first normal to increased
(because of inflammation) but is ultimately decreased.
_In most cases the end-stage
picture is indistinguishable from secondary biliary cirrhosis or the cirrhosis that
follows chronic hepatitis from other causes._
FIGURE 18-31 Primary biliary cirrhosis.
A portal tract is markedly expanded by an infiltrate
of lymphocytes and plasma cells.
There is a granulomatous reaction to a bile duct undergoing destruction (florid duct lesion).
What is the clinical course of PBC?
The onset is extremely insidious, and patients may be symptom-free for many years.
Eventually, pruritus, fatigue, and abdominal discomfort develop, followed in time by secondary features:
skin pigmentation, xanthelasmas, steatorrhea, and vitamin D malabsorption–related osteomalacia and/or osteoporosis.
More general features of jaundice and hepatic
decompensation, including portal hypertension and variceal bleeding, mark entry into the end
stages of the disease.
PBC patients have an increased risk to develop hepatocellular carcinomas. The major cause of death is liver failure, followed in order by massive variceal
hemorrhage and intercurrent infection.
Individuals with PBC may also have extrahepatic
manifestations of autoimmunity, including the sicca complex of dry eyes and mouth (Sjögren
syndrome; from the Latin sicca, meaning dryness), systemic sclerosis, thyroiditis, rheumatoid
arthritis,
Raynaud phenomenon, membranous glomerulonephritis, and celiac disease.
What is the therapy for PBC?
There is no specific therapy for PBC but treatment with ursodeoxycholic acid, if started early, can provide
complete remission and prolong survival is 25% to 30% of cases.
Its mechanism of action is not
well understood.
Liver transplantation is the best form of treatment for persons with end-stage
liver disease.
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PRIMARY BILIARY CIRRHOSIS (PBC)
