Antimitochondrial Antibody–Negative Primary Biliary Cirrhosis

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There is a subset of patients who have biochemical and histologic features consistent with primary biliary cirrhosis (PBC) who lack antimitochondrial antibodies (AMA). This entity is usually referred to as AMA-negative PBC or alternatively autoimmune cholangitis. Patients who have AMA-negative PBC are believed to have a similar clinical course, response to treatment, and prognosis as their AMA-positive counterparts. As more sensitive and specific serologic tests are developed to detect serum AMA, it is possible we may find that these patients initially believed to be AMA-negative are indeed AMA-positive, suggesting a single disease process.

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Clinical and Biochemical Features

AMA-negative PBC, like AMA-positive PBC, occurs predominantly in middle-aged women and is commonly asymptomatic. When symptoms are present, fatigue, pruritus, and symptoms of sicca syndrome are common initial features, whereas jaundice is usually a late finding. Elevation of the alkaline phosphatase is the typical biochemical feature, with transaminases being only mildly elevated. Several studies comparing the clinical and laboratorial findings between patients who have AMA-negative PBC and

Serologic Features

Some serologic characteristics aside from the absence of the antimitochondrial antibody may be different between AMA-negative and -positive PBC.

Several studies have reported a significantly higher rate of positivity for antinuclear antibodies (ANA) and smooth muscle antibodies (SMA) in patients who have AMA-negative PBC than that seen in AMA-positive PBC. In the different studies the prevalence of ANA ranged between 71% to 100%, and of SMA between 14% to 41% in patients who had AMA-negative

Histopathologic Features

According to the current thinking classic PBC and AMA-negative PBC share the same histologic features, but minor differences might emerge as more experience is gained in the latter group. Some authors have identified differences in the inflammatory infiltrates of patients who have AMA-negative and AMA-positive PBC [10], [11].

Ludwig [12] proposes applying the same criteria for diagnosis and staging used for PBC to AIC or AMA-negative PBC. Stage 1 (portal stage) is characterized by infiltration

Response to Treatment

The treatment of PBC involves two treatment modalities: ursodeoxycholic acid (UDCA) and orthotopic liver transplantation (OLT). UDCA has been shown to improve liver biochemistry and to slow disease progression, delaying time to death or liver transplantation in patients who have PBC, especially in those who have earlier-stage disease [13], [14]. In patients who have end-stage liver disease from PBC, OLT has been shown to prolong survival and to improve quality of life [15], [16]. Given the

Prognosis

Several models to predict survival in patients who have PBC have been developed [18], [19], [20]; the Mayo risk score is the most widely validated. It takes into account age, total bilirubin, serum albumin, prothrombin time, and presence or absence of edema [19]. Although these models have not been validated specifically in the AMA-negative population, it is reasonable to use them in this setting, given that most of the evidence available supports that the prognosis and natural history of

Summary

AMA-negative PBC, also known as AIC, shares similar clinical, biochemical, histologic, and prognostic features with classic PBC. Management of AMA-negative PBC should not differ from treatment of AMA-positive disease. The development of more sensitive and specific assays and increased understanding of the immunopathogenetic mechanisms of these diseases may, in the near future, prove them to be the same disease entity.

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