Chapter 18- Intrahepatic Biliary Tract Disease: PRIMARY BILIARY CIRRHOSIS (PBC) Flashcards
What is PSC?
PSC is characterized by inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts, with dilation of preserved segments.
What is the reason for the characteris “beading” of a contrast medium in radiographs of of the intrahepatic and extrahepatic biliary tree in PSC?
Characteristic “beading” of a contrast medium in
radiographs of the intrahepatic and extrahepatic biliary tree is attributable to the irregular strictures and dilations of affected bile ducts.
PSC is commonly seen in association with what diease?
inflammatory bowel disease (see Chapter 17 ), particularly chronic ulcerative colitis, which
coexists in approximately 70% of individuals with primary sclerosing cholangitis.
Conversely, the prevalence of PSC in persons with ulcerative colitis is about 4%. PSC tends to occur in the third through fifth decades of life, and males predominate 2 : 1. (See Table 18-8 for comparisons with
primary and secondary biliary cirrhosis.)
What is the pathology of PSC?
Primary sclerosing cholangitis is a chronic cholestatic disorder characterized by non-specific
inflammation, fibrosis and strictures of intra- and extrahepatic bile ducts. [57]
Several features
of the disease suggest that it results from immunologically mediated injury to bile ducts.
These include the detection of T cells in the periductal stroma, the presence of a plethora of
circulating autoantibodies, and theassociation with ulcerative colitis.
It has been proposed that
T cells activated in the gut mucosa travel to the liver where they recognize a bile duct antigen
that cross-reacts with gut antigens.
Another proposed etiology is that the bile duct lesions are a consequence of cross-reaction of bile duct antigens with enteric bacteria or bacterial products.
Antibodies commonly found in patients with primary sclerosing cholangitis include what?
- anti-smooth muscle antibodies,
- anti-nuclear antibodies (ANAs),
- rheumatoid factor, and an
- atypical p-ANCA which shows a perinuclear staining pattern but is directed against a nuclear envelope protein,
- instead of myeloperoxidase as is typical of p-ANCA antibodies.
- The atypical p-ANCA is found in up to 80% of patients, but its relationship with the pathogenesis of the disease is unknown.
First degree relatives of patients with primary sclerosing cholangitis have an increased risk of developing the disease.
As with many other immunologically mediated diseases, primary
sclerosing cholangitis is associated with an increased prevalence of certain MHC class I and
class II haplotypes
What is the morphology of PSC?
PSC is a fibrosing cholangitis of bile ducts, with a lymphocytic infiltrate, progressive atrophy of the bile duct epithelium, and obliteration of the lumen ( Fig. 18-32 ).
The concentric periductal fibrosis around affected ducts (“onion-skin fibrosis”) is followed by
their disappearance, leaving behind a solid, cordlike fibrous scar.
In between areas of progressive stricture, bile ducts become ectatic and inflamed, presumably the result of
downstream obstruction.
As the disease progresses the liver becomes markedly cholestatic, culminating in biliary cirrhosis much like that seen with primary and secondary biliary cirrhosis
FIGURE 18-32 Primary sclerosing cholangitis. A bile duct undergoing degeneration is
entrapped in a dense, “onion-skin” concentric scar.
What are the clinical features of PSC?
Asymptomatic patients may come to attention only because of persistent elevation of serum
alkaline phosphatase.
Alternatively, progressive fatigue, pruritus, and jaundice may develop.
The disease follows a protracted course of 5 to 17 years, and the severely afflicted patients have the usual symptoms of chronic liver disease, including weight loss, ascites, variceal
bleeding, and encephalopathy.
Approximately 7% of individuals with PSC develop
cholangiocarcinoma, a very high frequency relative to that of the general population.
The
incidence of chronic pancreatitis and hepatocellular carcinoma also seems to be increased in PSC patients.
A distinctive type of sclerosing cholangitis, with elevated IgG4 and associated with
autoimmune pancreatitis, has been recognized recently. [59]
What is the therapy for PSC?
There is no specific medical
therapy for PSC.
Cholestyramine has been used for pruritus, and endoscopic dilation with sphincterotomy or stenting is used for relieving symptoms.
Liver transplantation is the definitive
treatment for persons with end-stage liver disease.
