Primary Biliary Cirrhosis

Of unknown pathogenesis, primary biliary cirrhosis is probably neither autoimmune nor infectious in origin, although it is associated with autoimmune hepatitis. A strong association exists with antimitochondrial antibodies (AMAs), yet some patients are AMA negative and antinuclear antibody positive; the latter is also called autoimmune cholangitis (or cholangiopathy) rather than primary biliary cirrhosis.
Whether patients with so-called autoimmune cholangitis (i.e., those with an absence of antimitochondrial antibodies) should be consigned to a separate disease entity or considered to have a variant of primary biliary cirrhosis is conjecture (autoimmune cholangitis is also discussed in Chapter 8). Few differences are evident in clinical and serologic features in AMA-negative
and AMA-positive primary biliary cirrhosis patients.
A relationship exists between primary biliary cirrhosis and Sjögren’s syndrome. In fact, Sjögren’s syndrome is one of the most frequent extrahepatic associations of primary biliary cirrhosis, and some investigators consider that
primary biliary cirrhosis is a secondary form of Sjögren’s syndrome. Celiac sprue appears to be more common among patients with primary biliary cirrhosis than the general population. A rare patient also has chronic autoimmune gastritis or idiopathic thrombocytopenic purpura.
No association is believed to exist with inflammatory bowel disease, which distinguishes this condition from sclerosing cholangitis.
Pregnancy probably has no effect on disease activity. Pulmonary alveolar diffusion capacity is often impaired in these patients, although such
impairment is usually asymptomatic. An association between primary biliary cirrhosis and bronchial asthma has been reported. Severe hypoxemia has developed. Patients with primary biliary cirrhosis are believed not to be at increased risk for developing hepatocellular carcinoma. Nevertheless,
hepatocellular carcinoma and even a cholangiocarcinoma does occur occasionally.
The majority of patients are middle-aged women.Typically an early prodromal stage with mild elevation of liver function tests leads to cholestasis, although some patients are symptomatic even prior to cholestasis.
Sacral insufficiency fractures have developed in women with primary biliary cirrhosis.
Pathology
Progressive destruction of intrahepatic bile ducts, surrounding inflammation, and intrahepatic bile stasis mark primary biliary cirrhosis. Liver granulomas are a characteristic feature. The granulomas are noncaseating and onnecrotizing, consisting of epithelioid cells and occasional giant cells. These granulomas are not pathognomonic and are found in other disorders,
including primary sclerosing cholangitis.
The extrahepatic bile ducts are not involved. The intrahepatic bile ducts attenuate and, with progression, become somewhat tortuous and
splayed, presumably due to adjacent regenerating nodules. Histologically, the bile duct wall is not as thickened as in sclerosing cholangitis.
Nodular regenerative hyperplasia is common. Imaging Imaging differentiation between primary biliary cirrhosis and sclerosing cholangitis is
generally straightforward. A cholangiographic “pruned-tree” appearance gradually becomes evident (); the exception is in a minority of patients with sclerosing cholangitis who have involvement only of small intrahepatic
ducts; a gradual obliteration of these ducts may eventually lead to an appearance mimicking primary biliary sclerosis.
Computed tomography initially detects an enlarged or normal-size liver having a smooth contour; fibrosis and regenerative nodules are evident in about one third. Varices and ascites gradually develop. With advanced disease, CT findings are similar to those seen in other types of cirrhosis, except for a higher prevalence of diffuse liver enlargement.
A MR periportal halo sign is helpful in identifying this entity (). This sign, consisting of a hypointense focus centered around a portal vein branch and identified either on T1- or T2-weighted images, was found in 43% of patients with primary biliary cirrhosis awaiting transplantation but in no other cirrhotic
patients. mputed tomography identifies lymphadenopathy in about 90% of patients with primary biliary cirrhosis requiring orthotopic liver transplantation (49). Adenopathy usually involves periportal and hepatoduodenal ligament
nodes, and such adenopathy must be differentiated from that seen with neoplasms. A rough correlation exists between the size of the hepatoduodenal ligament lymph nodes and the degree of hepatocellular damage.
Therapy
The most common causes of death in patients with primary biliary cirrhosis are hepatic failure and gastrointestinal bleeding from varices. Currently no definitive therapy is available aside from liver transplantation. Transplantation has had a significant impact on patient survival.Nevertheless, the histologic features suggestive of recurrence develop in some transplant patients, with the recurrence rate apparently influenced by the type of immunosuppression used. During follow-up after orthotopic liver transplantation, 4% of patients developed recurrence .

Primary biliary cirrhosis. Only limited intrahepatic
bile ducts are filled in spite of a vigorous contrast injection.

Primary biliary cirrhosis. Transverse T1-weighted
MRI reveals round,hypointense lesions surrounding portal veins
(arrows), a finding termed the periportal halo sign.

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