Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Liver Disease or Hepatitis of Unknown Etiology Testing Algorithm
Clinical Background
Primary biliary cirrhosis (PBC) is an autoimmune liver disorder characterized by chronic, progressive cholestatic disease.
Epidemiology
- Incidence - 25-27/1,000,000 in U.S.
- Age - peak onset 40-50 years
- Gender - F>M
Risk Factors
- Presence of another autoimmune disorder
- Family history of PBC
- The relative risk of a family member of a first-degree relative of a PBC patient is 50- to 100-fold higher than the general population
Pathophysiology
- Etiology is unknown
- Pathogenesis of PBC is believed to be caused by:
- Defect in immune tolerance resulting in the expansion of self-mitochondrial antigen specific for T and B lymphocytes
- Inappropriate immune response following environmental or infectious agent causes modification of mitochondrial proteins or molecular mimicry
- PBC is characterized by T-cell mediated destruction of bile duct epithelial cells resulting in loss of ducts and persistent cholestasis which may result to end-stage liver failure without treatment.
Clinical Presentation
- Fatigue, pruritus, unexplained hyperlipidemia
- Elevated hepatic enzymes
- Complications
- Osteoporosis
- Esophageal varices
- Hepatocellular carcinoma
- Associated frequently with other autoimmune disorders such as:
- CREST
- Raynaud disease
- Sicca syndrome
- Autoimmune thyroid disease
- IgA deficiency
- Chronic autoimmune hepatitis (AIH)
- PBC and AIH have many overlapping immunologic features
- Some patients may have serologic tests and histologic findings suggestive of AIH in addition to PBC
- They may represent a continuum of a single disease entity
- Addison disease
- Systemic lupus erythematosus (SLE)
- Rheumatoid arthritis
- Scleroderma
Treatment
- Medical therapy
- Ursodeoxycholic acid does not reduce the risk for mortality or liver transplantation
- Cholestyramine for pruritis
- Liver transplantation for endstage cirrhosis
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Liver Disease or Hepatitis of Unknown Etiology Testing Algorithm
Diagnosis
Diagnosis
- Indications for testing - chronic pruritis, jaundice
- Laboratory testing
- PBC is strongly associated with antimitochondrial antibody (AMA), M2 type
- However, M2 levels in PBC do not appear correlated with clinical activity or disease progression
- Approximately 5-10% of PBC patients are AMA negative
- PBC is also associated with anti-sp100 (20-30%) of patients and anti-gp210 (15-27% of patients)
- Both antibodies are highly specific for PBC
- Histology - biopsy is not always indicated but does allow severity of disease classification
- Imagining studies
- If AMA negative and PBC is suspected, endoscopic retrograde cholangiopancreatography (ERCP), cholangiography or magnetic resonance cholangiopancreatography should be preformed
Disease Monitoring
- Anti-gp210 is prognostic in PBC
- Failure to see a decline with treatment increases risk of progression to end stage hepatic failure
Differential Diagnosis
- Autoimmune hepatitis
- Biliary carcinoma
- Cholelithiasis
- Chronic hepatitis
- Nonalcoholic fatty liver disease
- Primary sclerosing cholangitis (PSC)
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Liver Disease or Hepatitis of Unknown Etiology Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Mitochondrial M2 Antibody, IgG (ELISA)
|
| ARUP #: 0050065 |
| Methodology: Enzyme-Linked Immunosorbent Assay
|
| Use: Aid in the diagnosis of primary biliary cirrhosis (PBC) |
| Limitations: A negative M2 antibody result does not rule out PBC; about 5-10% of these patients are seronegative |
| Follow-up: |
| Test name: gp210 & sp100 Antibodies, IgG
|
| ARUP #: 0051636 |
| Methodology: Enzyme-Linked Immunosorbent Assay
|
| Use: Aid in the diagnosis of patients suspected of having PBC, especially for those who are anti-mitochondrial autoantibody negative (detects autoantibody against sp100 and gp210) |
| Limitations: Negative likelihood ratio for sp100 and gp 210 is 1.3 |
Additional Tests Available
| Test name: sp100 Antibody, IgG
|
| ARUP #: 0051625 |
| Methodology: Enzyme-Linked Immunosorbent Assay
|
| Comments: |
| Test name: gp210 Antibody, IgG
|
| ARUP #: 0051621 |
| Methodology: Enzyme-Linked Immunosorbent Assay
|
| Comments: |
| Test name: Centromere Antibody, IgG
|
| ARUP #: 0050714 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Comments: |
References
General References
Czaja AJ. Autoantibodies in autoimmune liver disease. Adv Clin Chem.
2005;
40:
127-164.
Gong Y, Huang Z, Christensen E, Gluud C. Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses. Am J Gastroenterol.
2007;
102(
8):
1799-1807.
Ishibashi H, Shimoda S, Gershwin ME. The immune response to mitochondrial autoantigens. Semin Liver Dis.
2005;
25(
3):
337-346.
Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med.
2005;
353(
12):
1261-1273.
Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T, Ueki T, Daikoku M, Yano K, Matsumoto T, Migita K, Yatsuhashi H, Ito M, Masaki N, Adachi H, Watanabe Y, Nakamura Y, Saoshiro T, Sodeyama T, Koga M, Shimoda S, Ishibashi H. Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J Hepatol.
2005;
42(
3):
386-392.
Parikh-Patel A, Gold E, Mackay IR, Gershwin ME. The geoepidemiology of primary biliary cirrhosis: contrasts and comparisons with the spectrum of autoimmune diseases. Clin Immunol.
1999;
91(
2):
206-218.
Reshetnyak VI. Concept on the pathogenesis and treatment of primary biliary cirrhosis. World J Gastroenterol.
2006;
12(
45):
7250-7262.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Layfield LJ, Cramer H. Primary sclerosing cholangitis as a cause of false positive bile duct brushing cytology: report of two cases. Diagn Cytopathol.
2005;
32(
2):
119-124.
Medical Reviewers
Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah
Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah
Tebo, Anne E., Ph.D. Assistant Medical Director, Immunology at ARUP Laboratories; Clinical Assistant Professor, Clinical Pathology, University of Utah
Comprehensive Review: September 2008
Last Update: September 2008
