Hepatitis Virus Tests
Viral hepatitis is any type of liver inflammation caused by a viral infection. The three most common viruses now recognized to cause liver disease are hepatitis A, hepatitis B, and hepatitis non-A, non-B (also called hepatitis C). Several other types have been recognized: hepatitis D, hepatitis E, and the recently identified hepatitis G. A seventh type (hepatitis F) is suspected but not yet confirmed.
The different types of viral hepatitis produce similar symptoms, but they differ in terms of transmission, course of treatment, prognosis, and carrier status. When the clinical history of a patient is insufficient for differentiation, hepatitis virus tests are used as an aid in diagnosis and in monitoring the course of the disease. These tests are based primarily on antigen-antibody reactions—an antigen being a protein foreign to the body, and an antibody another type of protein manufactured by lymphocytes (a type of white blood cell) to neutralize the antigen.
There are five major types of viral hepatitis. The diseases, along with the antigen-antibody tests available to aid in diagnosis, are described below.
Commonly called infectious hepatitis, this is caused by the hepatitis A virus (HAV). It is usually a mild disease, most often spread by food and water contamination, but sometimes through sexual contact. Immunologic tests are not commercially available for the HAV antigen, but two types of antibodies to HAV can be detected. IgM antibody (anti-HAV/IgM), appears approximately three to four weeks after exposure and returns to normal within several months. IgG (anti-HAV/IgG) appears approximately two weeks after the IgM begins to increase and remains positive. Acute hepatitis is suspected if IgM is elevated; conversely, if IgG is elevated without IgM, a convalescent stage of HAV is presumed. IgG antibody can remain detectable for decades after infection.
Commonly known as serum hepatitis, this is caused by the hepatitis B virus (HBV). The disease can be mild or severe, and it can be acute (of limited duration) or chronic (ongoing). It is usually spread by sexual contact with another infected person, through contact with infected blood, by intravenous drug use, or from mother to child at birth.
HBV, also called the Dane particle, is composed of an inner protein core surrounded by an outer protein capsule. The outer capsule contains the hepatitis B surface antigen (HBsAg), formerly called the Australia antigen. The inner core contains HBV core antigen (HBcAg), and the hepatitis B e-antigen (HBeAg). Antibodies to these antigens are called anti-HBs, anti-HBc, and anti-HBe. Testing for these antigens and antibodies is as follows:
- Hepatitis B surface antigen (HBsAg). This is the first test for hepatitis B to become abnormal. HBsAg begins to elevate before the onset of clinical symptoms, peaks during the first week of symptoms, and usually disappears by the time the accompanying jaundice (yellowing of the skin and other tissues) begins to subside. HBsAg indicates an active HBV infection. A person is considered to be a carrier if this antigen persists in the blood for six or more months.
- Hepatitis B surface antibody (anti-HBs). This appears approximately one month after the disappearance of the HBsAg, signaling the end of the acute infection period. Anti-HBs is the antibody that demonstrates immunity after administration of the hepatitis B vaccine. Its presence also indicates immunity to subsequent infection.
- Hepatitis B core antigen (HBcAg). No tests are commercially available to detect this antigen.
- Hepatitis B core antibody (anti-HBc). This appears just before acute hepatitis develops and remains elevated (although it slowly declines) for years. It is also present in chronic hepatitis. The hepatitis B core antibody is elevated during the time lag between the disappearance of the hepatitis B surface antigen and the appearance of the hepatitis B surface antibody in an interval called the "window." During this time, the hepatitis B core antibody is the only detectable marker of a recent hepatitis B infection.
- Hepatitis B e-antigen (HBeAg). This is more useful as an index of infection than for diagnostic purposes. The presence of this antigen correlates with early and active disease, as well as with high infectivity in patients with acute HBV infection. When HBeAg levels persist in the blood, the development of chronic HBV infection is suspected.
- Hepatitis B e-antibody (anti-HBe). In the bloodstream, this indicates a reduced risk of infectivity in patients who have previously been HBeAg positive. Chronic hepatitis B surface antigen carriers can be positive for either HBeAg or anti-HBe, but are less infectious when anti-HBe is present. Antibody to e antigen can persist for years, but usually disappears earlier than anti-HBs or anti-HBc.
Previously known as non-A, non-B hepatitis, this disease is primarily caused by the hepatitis C virus (HCV). It is generally mild, but more likely than hepatitis B to lead to chronic liver disease, possible liver failure, and the eventual need for transplant. Chronic carrier states develop in more than 80% of patients, and chronic liver disease is a major problem. As many as 20% of patients with chronic hepatitis C will develop liver failure or liver cancer. HCV is spread through sexual contact, as well as through sharing drug needles, although nearly half of infections can't be traced as to origin.
Hepatitis C is detected by HCV serology (tests on blood sera). A specific type of assay called enzyme-linked immunosorbent assay (ELISA) was developed to detect antibody to hepatitis C for diagnostic purposes, as well as for screening blood donors. Most cases of post-transfusion non-A, non-B hepatitis are caused by HCV, but application of this test has virtually eliminated post-transfusion hepatitis. An HCV viral titer to detect HCV RNA in the blood is now available, and recently, IgM anti-HCV core is proving to be a useful acute marker for HCV infection.
Also called delta hepatitis, this is caused by the hepatitis D virus (HDV). The disease occurs only in those who have HBV in the blood from a past or simultaneously occurring infection. Experts believe transmission may occur through sexual contact, but further research is needed to confirm that. Most cases occur among those who are frequently exposed to blood and blood products. Many cases also occur among drug users who share contaminated needles. Hepatitis D virus (HDV) antigen can be detected by radioimmunoassay within a few days after infection, together with IgM and total antibodies to HDV.
Caused by the hepatitis E virus (HEV), this is actually another type of non-A, non-B hepatitis. The virus is most often spread through fecally contaminated water, but the role of person-to-person transmission is unclear. This form of hepatitis is quite rare in the United States. There are currently no antigen or antibody tests widely available to accurately detect HEV.
Hepatitis virus tests require a blood sample. It is not necessary for the patient to withhold food or fluids before any of these tests, unless requested to do so by the physician.
Risks for these tests are minimal for the patient, but may include slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).
Reference ranges for the antigen/antibody tests are as follows:
- hepatitis A antibody, IgM: Negative
- hepatitis B core antibody: Negative
- hepatitis B e antibody: Negative
- hepatitis B e-antigen: Negative
- hepatitis B surface antibody: Varies with clinical circumstance (Note: As the presence of anti-HBs indicates past infection with resolution of previous hepatitis B infection, or vaccination against hepatitis B, additional patient history may be necessary for diagnosis.)
- hepatitis B surface antigen: Negative
- hepatitis C serology: Negative
- hepatitis D serology: Negative.
Hepatitis A: A single positive anti-HAV test may indicate previous exposure to the virus, but due to the antibody persisting so long in the bloodstream, only evidence of a rising anti-HAV titer confirms hepatitis A. Determining recent infection rests on identifying the antibody as IgM (associated with recent infection). A negative anti-HAV test rules out hepatitis A.
Hepatitis B: High levels of HBsAg that continue for three or more months after onset of acute infection suggest development of chronic hepatitis or carrier status. Detection of anti-HBs signals late convalescence or recovery from infection. This antibody remains in the blood to provide immunity to reinfection.
Hepatitis C (non-A, non-B hepatitis): Anti-HBc develops after exposure to hepatitis B. As an early indicator of acute infection, antibody (IgM) to core antigen (anti-HBc IgM) is rarely detected in chronic infection, so it is useful in distinguishing acute from chronic infection, and hepatitis B from non-A, non-B.
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Janis O. Flores