Primary Biliary Cirrhosis Workup

  • Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 4, 2012
 

Laboratory Studies

  • An elevation of the aminotransferases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may be identified in most patients with primary biliary cirrhosis, but significant elevations of the alkaline phosphatase (ALP), γ -glutamyl transpeptidase (GGTP), and immunoglobulin levels (mainly immunoglobulin M [IgM]) are usually the most prominent findings.
  • Lipid levels and cholesterol levels may be increased, with an increased high-density lipoprotein (HDL) fraction. The latter finding explains why these patients do not have an increased risk for atherosclerosis.
  • An increased erythrocyte sedimentation rate is another finding.
  • As the disease progresses to cirrhosis, an elevated bilirubin level, a prolonged prothrombin time, and a decreased albumin level can be found. The increased bilirubin level is an ominous sign of disease progression, and liver transplantation must be considered.
  • Thrombocytopenia is indicative of portal hypertension. Additionally, but not as commonly, abnormalities include elevated levels of ceruloplasmin, bile acids, and serum hyaluronate.
  • The hallmark of this disease is the presence of antimitochondrial antibodies (AMAs) in the sera.
    • AMAs can be found in 90-95% of patients with primary biliary cirrhosis, and they have a specificity of 98% for this disease.
    • These antibodies target different components, mainly enzymes, in the mitochondria.
    • The presence of anti-M2, anti-M4, anti-M8, and anti-M9 has been associated with the severity of primary biliary cirrhosis. Patients with profile A (ie, only anti-M9) or profile B (ie, anti-M9 and/or anti-M2–positive by enzyme-linked immunosorbent assay [ELISA]) have a better disease course than patients with profile C (ie, anti-M2, anti-M4, and/or anti-M8–positive by ELISA) and profile D (ie, anti-M2, anti-M4, and/or anti-M8–positive by ELISA and complement-fixation test).
    • Antinuclear antibodies (ANAs) can be identified in 20-50% of patients with primary biliary cirrhosis.
    • Some patients have clinical, biochemical, and histologic features of primary biliary cirrhosis, but their sera are negative for AMA. The diagnosis of autoimmune cholangitis has been used for these patients, but whether these patients represent the AMA-negative primary biliary cirrhosis group is a matter of debate. In terms of autoimmune markers, their profile is compatible with this type of autoimmune hepatitis (ie, high-titer ANA and/or SMA).
    • The natural history and associated autoimmune conditions in AMA-positive and AMA-negative primary biliary cirrhosis appear to be identical. A careful review of the liver biochemical pattern reveals cholestasis (ie, ALP and GGTP are elevated), and the liver biopsy findings are compatible with bile duct injury, ductopenia, cholestasis, and granulomas.[7]
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Imaging Studies

  • Abdominal ultrasonography, computed tomography (CT) scanning, or magnetic resonance imaging (MRI) are important to exclude biliary obstruction.
    • Nonspecific findings include increased echogenicity of the liver parenchyma and findings compatible with portal hypertension.
    • Portal lymphadenopathy can be recognized in approximately 15% of these patients.
    • Once patients are cirrhotic, findings compatible with portal hypertension (eg, nodular appearance of the liver, splenomegaly, intra-abdominal varices, ascites) can be observed. At this stage, follow-up imaging every 6 months with abdominal ultrasonography is suggested for early detection of hepatic malignancy.
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Procedures

  • The diagnosis of primary biliary cirrhosis should be established or confirmed by performing a percutaneous or laparoscopic liver biopsy. This procedure also provides additional information about the stage of the disease and the patient's prognosis.
  • In the late stages of the disease (ie, cirrhosis), an upper endoscopy study should be performed. If the patient has developed esophageal varices, prophylactic treatment (eg, beta-blockers, nitrates) can be initiated in an attempt to prevent variceal bleeding.
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Histologic Findings

Primary biliary cirrhosis is characterized by chronic, nonsuppurative, destructive cholangitis of the small interlobular bile ducts with a diameter of 40-80 mm. Early lesions signal damage of the basement membrane of the bile ducts and reactive hyperplasia of the epithelial lining. Lymphocytic and plasma cell infiltration, with eosinophilic condensation in the portal tracts, is another feature. Epithelioid aggregates or granulomas may be found around the bile ducts. Fibrosis and cirrhosis develop later.

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Staging

Various staging systems have been developed, but the most prominent are those proposed by Ludwig et al and Scheuer.[8]

  • Stage 1 (portal stage of Ludwig): Portal inflammation, bile duct abnormalities, or both are present.
  • Stage 2 (periportal stage): Periportal fibrosis is present, with or without periportal inflammation or prominent enlargement of the portal tracts with seemingly intact, newly formed limiting plates. See the image below. This histologic picture is compatible with stage 2This histologic picture is compatible with stage 2 primary biliary cirrhosis.
  • Stage 3 (septal stage): Septal fibrosis with active inflammatory, passive paucicellular septa, or both are present.
  • Stage 4 (cirrhosis): Nodules with various degrees of inflammation are present.
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Contributor Information and Disclosures
Author

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP  Chair of Hepatology, Medical Director of Liver Transplantation, Liver Unit, Florida Hospital; Associate Professor of Medicine, University of Central Florida College of Medicine

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Liver Foundation, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Transplantation, International Liver Transplantation Society, and Transplantation Society

Disclosure: Gilead Sciences Honoraria Speaking and teaching; Schering-Plough Honoraria Speaking and teaching; Roche Honoraria Speaking and teaching

Coauthor(s)

K Rajender Reddy, MD, FACP, FACG  Professor of Medicine, Director of Hepatology, Medical Director of Liver Transplantation, Hospital of the University of Pennsylvania

K Rajender Reddy, MD, FACP, FACG is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Florida Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

George Y Wu, MD, PhD  Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Gilead Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

James L Achord, MD  Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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This histologic picture is compatible with stage 2 primary biliary cirrhosis.
 
 
 
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