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Primary Biliary Cirrhosis View Online At Primary Biliary Cirrhosis View online at http://pier.acponline.org/physicians/diseases/d472/d472.html Module Updated: 2013-02-12 CME Expiration: 2016-02-12 Author Richard H. Moseley, MD Table of Contents 1. Screening ..........................................................................................................................2 2. Diagnosis ..........................................................................................................................3 3. Consultation ......................................................................................................................7 4. Hospitalization ...................................................................................................................8 5. Therapy ............................................................................................................................9 6. Patient Education ...............................................................................................................14 7. Follow-up ..........................................................................................................................15 References ............................................................................................................................16 Glossary................................................................................................................................20 Tables ...................................................................................................................................21 Quality Ratings: The preponderance of data supporting guidance statements are derived from: level 1 studies, which meet all of the evidence criteria for that study type; level 2 studies, which meet at least one of the evidence criteria for that study type; or level 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus. Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.html Disclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position of the American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete. Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the most current available. CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has been developed for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completion of the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthen their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Richard H. Moseley, MD, current author of this module, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA. Primary Biliary Cirrhosis Top 1. Screening Although general population screening for primary biliary cirrhosis is not indicated, consider screening certain family members of known patients. 1.1 Consider screening first-degree relatives of patients with PBC. Recommendations • Obtain blood levels of antimitochondrial antibody, alkaline phosphatase, ALT, and AST. Evidence • In a retrospective study, the prevalence of PBC in family members of patients with this disease was markedly increased when compared with estimates in the general population (1). • In one British study of 160 patients with PCB, improved methodology suggested that the overall prevalence of PBC in first-degree relatives of patients with PBC was less than 1%, similar to values seen in other autoimmune diseases. The highest prevalence was seen in daughters of patients (2). • An interview-based study of 1032 patients showed that having a first-degree relative with PBC is significantly associated with increased risk for PBC (3). • A concordance rate of 63% has been reported in monozygotic twins with PBC (4). • In a study from the U.S., 13.1% of first-degree relatives of patients with PBC tested positive for antimitochondrial antibodies (5). • Familial clustering of PBC has also been reported outside of the U.S and the United Kingdom (6). Rationale • Screening should be considered because the risk for PBC is increased in first-degree relatives of patients with PBC. PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA. Page 2 of 26 Primary Biliary Cirrhosis Top 2. Diagnosis Consider the diagnosis of PBC in patients with chronic cholestasis manifested by unexplained elevations of serum alkaline phosphatase or unexplained pruritus without a rash. 2.1 Recognize that the symptoms of PBC may be absent or nonspecific. Recommendations • Although patients with PBC may be asymptomatic, ask about: Factors associated with other autoimmune diseases, such as: o Sicca syndrome o CREST syndrome o Raynaud's phenomenon o Thyroid dysfunction o Rheumatoid arthritis o Celiac sprue Family history of cirrhosis Unexplained itching (pruritus) Unexplained fatigue Unexplained weight loss Urinary tract infections Medication history, including use of hormone replacement therapy Smoking history Evidence • Although fatigue and pruritus used to be the most common presenting symptoms of PBC, review articles indicate that the disease is now more widely recognized and many patients are diagnosed at earlier stages when they are asymptomatic (7; 8; 9). Fatigue may be a manifestation of untreated hypothyroidism, which occurs in approximately 20% of patients with PBC (8). • Approximately 50% to 60% of patients are asymptomatic at diagnosis (7; 8; 9; 10). • The cause of pruritus in PBC is unknown, but several hypotheses have been proposed, including bile acid accumulation and endogenous opioids (11). • A case-control study showed that smoking is strongly associated with PBC (OR, 2.04 [CI, 1.10 to 3.78]) (12). Rationale • Although PBC is uncommon, it can be diagnosed while asymptomatic and should be considered in patients with chronic cholestasis, especially patients who have other autoimmune diseases. • It is important to question patients about the use of medications, because some drugs may cause cholestasis similar to that associated with PBC. 2.2 Recognize that the clinical signs attributable to PBC may be absent or nonspecific. Recommendations • Although patients with PBC may have no clinical signs of the disease, look for: Fatigue Weight loss Hyperpigmentation PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA. Page 3 of 26 Primary Biliary Cirrhosis Xanthomas Hepatosplenomegaly, suggesting chronic liver disease Signs of advanced stage of liver disease, such as: o Spider nevi o Temporal and proximal limb muscle wasting o Ascites o Edema Jaundice, usually a later manifestation of the disease Evidence • Comprehensive review articles and guidelines emphasize that patients with certain elements in their history and physical exam may be more likely to have PBC. For example, pruritus, hyperpigmentation of the skin, and hepatomegaly in women with a cholestatic pattern of liver function tests are common in PBC but unusual in other liver disorders, such as acute and chronic hepatitis and alcoholic liver disease (7; 8; 9). • A case-control study showed that a significant proportion of patients with PBC suffer from severe fatigue, which correlates with the degree of daytime somnolence (13). Rationale • Although the signs of PBC are likely to be nonspecific if present, physical findings (e.g., hyperpigmentation, xanthomas, jaundice) may provide clues to the diagnosis, as well as an indication of the severity of liver disease. 2.3 Recognize laboratory abnormalities suggesting PBC. Recommendations • Look for the following laboratory abnormalities: Elevated serum alkaline phosphatase and/or gamma glutamyl transpeptidase levels Normal or elevated conjugated bilirubin levels Slightly elevated ALT and AST levels A positive antimitochondrial antibody test Elevated serum levels of total immunoglobulin M Elevated serum cholesterol level Elevated serum ceruloplasmin level Negative tests for hepatitis A, B, and C viruses Normal serum iron, total iron binding capacity, and iron saturation levels • See table Laboratory and Other Studies for Primary Biliary Cirrhosis. Evidence • A major advance in our understanding
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