Hepatitis: Serologic Tests
Last updated: November 9, 2014
CPT Codes: Hepatitis B surface antigen (HBsAg) 87340; Hepatitis A antibody (HAAb), IgM antibody 86709; Hepatitis B core antibody (HBcAb), IgM antibody 86705; Hepatitis C antibody 86803
Description: Serologic tests are used in the diagnosis and management of viral hepatitis A, B, and C. Serologic tests are also available for viral hepatitis D, E, and G, but they have limited clinical application in rheumatology.
Method: Methods include immunodiffusion, ELISA, recombinant immunoblot assays, PCRs, and branched DNA (bDNA) assays.
Normal Value. Tests are normally negative in healthy persons.
Abnormal in: Serologic pattern varies with hepatitis type and duration.
—Hepatitis A virus
• Antihepatitis A virus IgM is detected in acute hepatitis A. It appears with the onset of symptoms, is detectable for as long as 24 weeks, and confirms the diagnosis.
• Antihepatitis A virus IgG is detected after the acute period and persists for life. It indicates previous exposure, recovery, and immunity to hepatitis A.
—Hepatitis B virus
• Hepatitis B surface antigen (HBsAg) is the earliest indicator of HBV infection; it appears in 27 to 41 days, persists during acute illness, and disappears within 6 months with recovery. Persistence after 6 months
implies chronic carrier state.
• Antibody to HBsAg indicates clinical recovery and immunity to hepatitis B virus; it also appears after immunization against hepatitis B virus.
• Hepatitis B “e” antigen (HBeAg) is associated with infectivity. It appears shortly after HBsAg and disappears before HBsAg disappears, being present for 3 to 6 weeks. Persistence beyond 10 weeks suggests
progression to chronic carrier state, chronic hepatitis. Presence correlates with neonatal transmission of hepatitis B virus.
• Antibody to hepatitis B e antigen correlates with decreasing infectivity and good prognosis.
• Antibody to core antigen(HBcAb) includes antihepatitis B core total, antihepatitis B core IgM, and antihepatitis B core IgG. HBcAb early in infection and persists lifelong. The IgM component is found for a short time during acute viral infection and persists during the “window” period (after disappearance of HBsAg and before appearance of anti-HBs) and is thus a marker of recent infection. The IgG component persists lifelong and indicates prior exposure to HBV and is frequently referred to a “resolved” or “occult” HBV (HBsAg negative and HBcAb positive).
—Hepatitis C virus: Four assays are available for the diagnosis of hepatitis C virus: ELISA, recombinant immunoblot assays, PCR, and a bDNA assay:
• Antibody to hepatitis C virus (ELISA) reflects actual viral replication and infectivity rather than immunity. Its sensitivity is approximately 80% in chronic carriers and only approximately 15% in the first 6 months after acute infection. It is present in several high-risk groups: posttransfusion hepatitis (70%–85%), intravenous drug users (70%), patients on hemodialysis (20%), homosexual men positive for human
immunodeficiency virus-1 (8%). Its prevalence in normal blood donors is between 0.5% and 2%.
• Recombinant immunoblot assay is used as a supplemental test if the ELISA is borderline positive (differentiates false-positive from true positive results).
• PCR and bDNA assays both measure the amount of HCV. PCR efficiently detects very low levels of the virus.
| Table. Diagnostic Approach in Suspected Acute Viral Hepatitis | ||||
| Screening | Result | Secondary Test | Diagnosis* | |
|---|---|---|---|---|
|
Anti-HAVIgM HBsAg Anti-HBc IgM |
Positive Negative Negative |
Acute HAV infection | ||
|
Anti-HAV IgM HBsAg Anti-HBc IgM |
Negative Positive Negative |
Acute HBV | ||
|
Anti-HAV IgM HBsAg Anti-HBc IgM |
Negative Positive Negative |
Anti-HBc IgG positive Anti-HBc IgG negative |
Chronic HBV carrier Acute HBV |
|
|
Anti-HAV IgM HBsAg Anti-HBc IgM |
Negative Negative Positive |
Anti-HBs positive Anti-HBs negative |
Convalescence “Window” period; Resolved HBV infection |
|
|
Anti-HAV IgM HBsAg Anti-HBc IgM |
Negative Negative Negative |
Anti-HBs positive Anti-HBs negative |
Convalescence, immune, passive transfer Possible HCV infection |
|
| * Diagnosis based on screening and secondary test results. HAV, hepatitis A virus; IgM, immunoglobulin M; HBsAg, hepatitis B surface antigen; HBc, hepatitis B core. |
||||
Confounding Factors: False positives are common with anti-hepatitis C virus antibodies and are seen in many autoimmune diseases, with passive antibody transfer and prolonged blood storage. False negatives may occur in early infection and immunosuppression.
Indications: Serologic tests are used for diagnosis of acute hepatitis, screening potential blood donors or those initiating DMARD therapy (e.g., MTX, leflunomide, azathioprine, TNF inhibitors, rituximab, abatacept), gauging the response to therapy in chronic hepatitis, monitoring for immunization, investigation of polyarteritis nodosa (25% of cases, usually intravenous substance abusers, are HBsAg, anti-hepatitis B surface, or hepatitis C virus positive), suspected cryoglobulinemia (anti-hepatitis C virus or hepatitis C virus RNA occurs in more than 80% of patients with essential mixed cryoglobulinemia).
Cost: Hepatitis A virus antibody, $40–90; HBsAg, $55; hepatitis C virus anti-body, $85; hepatitis C virus recombinant immunoblot assay, $160–260.
Comments: Hepatitis C virus testing continues to improve with newer generations of ELISA and recombinant immunoblot assays, with decreasing numbers of false positives. A logical stepwise approach is preferred to indiscriminate testing.
BIBLIOGRAPHY
Wallach J. Hepatobiliary diseases and diseases of the pancreas. In: Interpretation of diagnostic tests, 6th ed. Boston: Little, Brown, 1996:187–205.
