Cirrosis Biliar Primaria

AASLD PRACTICE GUIDELINES Primary Biliary Cirrhosis
Keith D. Lindor,1 M. Eric Gershwin,2 Raoul Poupon,3 Marshall Kaplan,4 Nora V. Bergasa,5 and E. Jenny Heathcote6
This guideline has been approved by the AASLD and represents the position of the association. and the American Heart Association Practice Guidelines3).

Preamble
These recommendations provide a data-supported approach to themanagement of primary biliary cirrhosis (PBC). They are based on the following: (1) formal review and analysis of the recently published world literature on the topic (Medline search); (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines 1; (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and theAmerican Gastroenterological Association Policy Statement on Guidelines2; and (4) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in everycase. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting recommendations, the Practice Guideline Committee of the AASLD requires a Class (reflecting benefit versus risk) and Level (assessing strength or certainty) of Evidence to be assigned and reported with each recommendation (Table 1, adapted from the AmericanCollege of Cardiology

Etiology of Primary Biliary Cirrhosis
PBC is often considered a model autoimmune disease because of its hallmark serologic signature, the antimitochondrial antibody (AMA) and specific bile duct pathology.4,5 The etiology of PBC is thought to be due to a combination of genetic predisposition and environmental triggers.6 Although the genetic predisposition is clear, majorhistocompatibility complex associations are varied.7 Several large epidemiologic studies have been performed and have suggested an association with urinary tract infections, reproductive hormone replacement, nail polish, past cigarette smoking, and toxic waste sites, as well as xenobiotics in an animal model of PBC.8-10 One critical and unique feature of PBC is the high degree of specificity forinvolvement of the small intrahepatic bile ducts. Staining of small bile ducts with monoclonal antibodies against mitochondrial autoantigens demonstrates an intense staining at the apical surface of biliary epithelial cells.11,12 The characteristic serologic hallmark of PBC is the AMA, a highly disease-specific autoantibody found in 90%-95% of patients and less than 1% of normal controls.13 The targets ofthe disease-specific antimitochondrial response are all members of a family of enzymes, the 2-oxo-acid dehydrogenase complexes and include pyruvate dehydrogenase complex (PDC-E2), branched chain 2-oxo-acid dehydrogenase complex, and 2-oxo-glutaric acid dehydrogenase complex. These enzymes catalyze the oxidative decarboxylation of keto acid substrates and are located in the inner mitochondrialmembrane.14,15 Fewer than 5% of patients with PBC are AMA-negative in one study.16 Both immunofluorescence, and now more commonly enzyme-linked immunosorbent assays, are used to test for AMA. There is a 100-fold to 150-fold increase of autoreactive CD4 PDC-E2–specific T cells in liver and regional lymph node compared to blood in patients with PBC, and a 10-fold to 15-fold increase in autoreactive CD8PDCE2–specific T cell infiltrates in liver compared to blood. These data strongly suggest that the antimitochondrial response is either directly related to pathology or intimately associated with the etiological insult.17,18
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Abbreviations: AASLD, American Association for the Study of Liver Diseases; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; AST, aspartate aminotransferase;...