Screening Procedure
Hepatitis is an inflammation of the liver. The condition can be self-limiting or can progress to fibrosis (scarring), cirrhosis or liver cancer.
Hepatitis viruses are the most common cause of hepatitis in the world but other infections, toxic substances (e.g. alcohol, certain drugs), and autoimmune diseases can also cause hepatitis. There are 5 main hepatitis viruses, referred to as types A, B, C, D and E and other two types are Autoimmune Hepatitis, Alcoholic hepatitis.
In particular, types B and C lead to chronic disease in hundreds of millions of people and, together, are the most common cause of liver cirrhosis and cancer.
Scroll to Hepatitis A
Hepatitis A
This test is used to help diagnose a liver infection due to the hepatitis A virus (HAV). There are several causes of hepatitis and the accompanying symptoms, so this test may be used to determine if the symptoms are due to hepatitis A.
A few different versions of the test may be used to detect different classes of hepatitis A antibodies.
- The HAV IgM antibody test detects the first antibody produced by the body when it is exposed to hepatitis A. This test is used to detect early or recent infections and to diagnose the disease in people with symptoms of acute hepatitis. It may be performed as part of an acute viral hepatitis panel.
- The HAV IgG test detects the IgG antibodies that develop later in the course of the disease. IgG antibodies remain present for many years, usually for life, providing protection against recurrent infection by the same virus. The IgG test is used to detect past HAV infections and may occasionally be used to determine if an individual has developed immunity from a previous infection (immune status), in which case a vaccine is not necessary.
- The total HAV antibody test detects both IgM and IgG antibodies and thus may be used to identify both current and past infections. This test will also be positive after receiving the vaccine, so sometimes it may be used to determine whether a person has developed immunity after vaccination, though this practice is not advised. Recommendations of the Advisory Committee on Immunization Practices (ACIP) state that “post-vaccination testing is not indicated because of the high rate of vaccine response among adults and children. In addition, not all testing methods approved for routine diagnostic use in the United States have the sensitivity to detect low anti-HAV concentrations after vaccination.”
In acute hepatitis, other tests such as bilirubin, liver panel, ALT, and AST may be performed with viral hepatitis tests to help diagnose the condition.
What does the test result mean?
Results of hepatitis testing may indicate the following:
| HAV IgM | HAV IgG or Total Antibody (IgM and IgG) | Results Indicate |
|---|---|---|
| Positive | Not Performed | Acute or recent HAV infection |
| Negative | Positive | No active infection but previous HAV exposure; has developed immunity to HAV or recently vaccinated for HAV |
| Not Performed | Positive | Has been exposed to HAV but does not rule out acute infection |
| Not | Negative | No current or previous HAV infection; vaccine may be recommended if at risk |
| Performed | recommended if at risk |
Scroll to Hepatitis B
Hepatitis B
Hepatitis B virus (HBV) tests may be used for a variety of reasons. Some of the tests detect antibodies produced in response to HBV infection; some detect antigens produced by the virus, and others detect viral DNA.
The main uses for HBV tests include:
- To determine whether acute signs and symptoms are due to HBV infection; two tests, hepatitis B surface Ag and hepatitis B core antibody IgM, may be performed as part of an acute viral hepatitis panel along with tests for hepatitis A (HAV) and hepatitis C (HCV) to determine which virus may be causing the infection.
- To diagnose chronic HBV hepatitis
- To monitor chronic hepatitis B infection and its treatment
- To detect previous exposure to hepatitis B, in a person who is immune compromised (when the virus can become reactivated)
Some of the secondary reasons to perform testing include: to screen for hepatitis B infection in at-risk populations or in blood donors, to determine if someone is a carrier, to detect the previous infection (with subsequent immunity), and to determine if immunity has developed due to vaccination.
Generally, one set of tests is used as an initial panel of tests to detect HBV infection or to determine the cause of acute symptoms while another set of tests may be used after a diagnosis is made to monitor the possible progression of the disease, to detect chronic infection, and/or to determine carrier status.
The following table summarizes the set of tests typically used for initial testing:
| Test | Description | Use and Comments |
|---|---|---|
| Hepatitis B surface antigen (HBsAG) | Detects protein that is present on the surface of the virus | To screen for, detect, and help diagnose acute and chronic HBV infections; earliest routine indicator of acute hepatitis B and frequently identifies infected people before symptoms appear; undetectable in the blood during the recovery period; it is the primary way of identifying those with chronic infections, including “HBV carrier” state. |
| Hepatitis B surface antibody (anti-HBs) | Detects antibody produced in response to HBV surface antigen | Used to detect previous exposure to HBV; it can also develop from successful vaccination so it is used to determine the need for vaccination (if anti-HBs is absent) or to determine if a person has recovered from an infection and is immune (cannot get the infection again). |
| Total anti-hepatitis B core (anti-HBc, IgM and IgG) | Detects both IgM and IgG antibodies to hepatitis B core antigen | Can be used to help detect acute and chronic HBV infections; the IgM antibody is the first antibody produced after infection with HBV; IgG antibody is produced in response to the core antigen later in the course of the infection and usually persists for life. |
The following table summarizes tests that may be used as follow-up after initial tests detect an HBV infection:
| Test | Description | Use and Comments |
|---|---|---|
| Anti-hepatitis B core (anti-HBc), IgM | Detects only the IgM antibody to the hepatitis B core antigen | Used to detect acute infections; sometimes present in chronic infections as well |
| Hepatitis B e-antigen (HBeAG) | Detects protein produced and released into the blood | Often used as a marker of ability to spread the virus to other people (infectivity); it may also be used to monitor the effectiveness of treatment. However, there are some types (strains) of HBV that do not make e-antigen; these are especially common in the Middle East and Asia. In areas where these strains of HBV are common, testing for HBeAg is not very useful to determine whether the virus can be spread to others. |
| Anti-hepatitis B e antibody (Anti-HBe) | Detects antibody produced by the body in response to the hepatitis B “e” antigen | Used to monitor acute infections in those who have recovered from acute hepatitis B infection; anti-HBe will be present along with anti-HBc and anti-HBs. |
| Hepatitis B viral DNA | Detects hepatitis B viral genetic material in the blood | A positive test indicates that the virus is multiplying in a person's body and that person is highly contagious. The test is often used to monitor the effectiveness of antiviral therapy in people with chronic HBV infections. |
| Hepatitis B virus resistance mutations | Detects mutations in the particular virus causing a person’s infection that allows the virus to be resistant to treatments (reverse transcriptase inhibitors) | Helps to select appropriate treatment, especially in people who have been treated previously or in those who are not responding to treatment |
While the tests described above are specific for HBV, other liver tests such as AST, ALT, and gamma-glutamyl transferase (GGT) may be used to monitor the progress of the disease. In some cases, a liver biopsy may be performed to evaluate how much damage has occurred to the liver.
What does the test result mean?
The tests for hepatitis B may be ordered individually but are often ordered in some combination, depending on the reason for testing. Results of the tests are typically evaluated together. Sometimes the meaning of one result depends on the result of another test. However, not all tests are performed for all people.
The table below summarizes possible interpretations of some common patterns of results.
| Initial Tests | Follow-up Tests | ||||||
|---|---|---|---|---|---|---|---|
| Hep B surface antigen (HBsAg) | Hep B surface antibody (Anti-HBs) | Hep B core antibody Total (Anti-HBc IgG+IgM) | Hep B core antibody (Anti-HBc IgM) | Hep B e antigen (HBeAg)* | Hep B e antibody (Anti-HBe) | HBV DNA | Possible Interpretation / Stage of Infection |
| Negative | Negative | Negative | Not performed | Not performed | Not performed | Not performed | No active or prior infection; not immune - may be good candidate for vaccine; possibly in the incubation stage |
| Negative | Positive | Negative | Not performed | Not performed | Not performed | Not performed | Immunity due to vaccination |
| Negative | Positive | Positive | Not performed | Not performed | Not performed | Not performed | Infection resolved (recovery), virus cleared; immunity due to natural infection. However, if immunosuppressed, virus can reactivate. |
| Positive | Negative | Positive or Negative | Positive or Negative | Positive | Negative | Detected or none detected | Acute infection, usually with symptoms; contagious; could also be flare of chronic infection |
| Negative | Negative | Positive | Negative | Negative* | Positive | None detected | Acute infection is resolving (convalescent) |
| Positive | Negative | Positive | Negative | Positive | Negative | Detected | Usually indicates an active chronic infection (liver damage likely) |
| Positive | Negative | Positive | Negative | Negative* | Positive | None detected or detected at very low level | Chronic infection but low risk of liver damage - carrier state |
Scroll to Hepatitis C
Hepatitis C
Hepatitis C tests are used to screen for and diagnose a hepatitis C virus (HCV) infection, to guide therapy and/or to monitor the treatment of an HCV infection.
An HCV antibody test is used to screen for past exposure and current infection. It detects the presence of antibodies to the virus, indicating exposure to HCV. This test cannot distinguish whether someone has an active or a previous HCV infection. There is some evidence that if the test is “weakly positive,” it may be a false positive. The Centers for Disease Control and Prevention (CDC) recommends that all positive antibody tests be followed by an HCV RNA test that detects viral RNA in the blood to determine whether or not the person has an active infection.
The HCV antibody test may be performed as part of an acute viral hepatitis panel to determine which of the most common hepatitis viruses is causing a person’s symptoms.
The following tests may be used to diagnose a current infection and to guide and monitor treatment:
- HCV RNA tests:
- HCV RNA test, Quantitative (HCV viral load) detects and measures the number of viral RNA particles in the blood. This test may be used to confirm the presence of the virus and diagnose an active infection. Viral load tests are also used before and during treatment to help determine response to therapy by comparing the amount of virus before and during treatment.
- HCV RNA, Qualitative is used to distinguish between a current or past infection. It is reported as a “positive” or “detected” if any HCV viral RNA is found; otherwise, the report will be “negative” or “not detected.” This test is not frequently used anymore.
- Viral genotyping is used to determine the kind, or genotype, of the HCV present to help guide treatment. There are 5 major types of HCV and more than 50 subtypes identified; the most common, genotype 1, accounts for about 75% of cases in the U.S. The drugs selected for treatment depend in part on the genotype of HCV infecting a person.
Scroll to Hepatitis D
What does the test result mean?
An HCV antibody test is typically reported as “positive” or “negative”.
Results of HCV viral load testing are reported as a number if virus is present. If no virus is present or if the amount of virus is too low to detect, the result is often reported as “negative” or “not detected”.
Interpretation of the HCV screening and follow-up tests is shown in the table below. In general, if the HCV antibody test is positive, then the individual tested is infected or has likely been infected at some time with hepatitis C. If the HCV RNA test is positive, then the person has a current infection. If no HCV viral RNA is detected, then the person either does not have an active infection or the virus is present in very low numbers.
| HCV Antibody | HCV RNA | HCV Infection |
|---|---|---|
| Negative | No infection or too early after exposure for the test to be accurate; if suspicion remains high, retesting at a later time may be required. | |
| Positive or Indeterminate | Negative | Past infection or no infection (false-positive screen); additional testing if indicated |
| Positive or Weak or Indeterminate | Positive | Current infection |
For monitoring purposes, an HCV viral load (HCV RNA quantitative) can indicate whether or not treatment is effective. A high or increasing viral load may be a sign that treatment is not successful whereas a low, decreasing, or undetectable viral load may imply that the treatment is working.
The successful treatment causes a decrease of 99% or more in viral load soon after starting treatment (as early as 2-4 weeks) and usually leads to undetectable viral load after treatment is completed. According to guidelines from the American Association for the Study of Liver Diseases and the Infectious Disease Society of America, an undetectable viral load in a treated person’s blood 12 weeks after the end of the treatment means that the HCV infection has responded to therapy.
The results of the HCV genotype test identifies which strain of HCV the person has and helps guide the selection and the length of treatment. Treatments may differ depending on a variety of factors, including HCV genotype and the health of the person’s liver.
Hepatitis D
Laboratory Testing
- Hepatitis Delta virus (HDV) antibody tests
- Positive in acute disease; should be followed by HDV antigen (HDsAg) testing, IgM antibody by EIA or ELISA and by HBsAg to confirm persisting chronic HBV
- In acute coinfections, HDsAg appears early, after HBV virus surface antigen, and disappears with convalescence
- Acute HDV infections are associated with anti-HDV IgM antibody
- Usually, only chronic cases demonstrate IgG antibody
- Both antibodies usually disappear following convalescence
- Simultaneous assessment of anti-HBV HBsAg core antibody IgM and HDsAg helps differentiate coinfections (present) from superinfections (absent)
- PCR – confirm and quantify the presence of HDV
Prognosis
- Based on the following
- Modality of infection (coinfection vs. superinfection)
- HDV genotype
- Type 3 associated with more severe disease
- HBV replication by RNA or ELISA
- Higher numbers associated with more severe disease
Scroll to Hepatitis E
Hepatitis E
Elevation in the serum aminotransferase levels is the laboratory hallmark of acute viral hepatitis. Serum alanine aminotransferase (ALT) level is usually higher than the serum aspartate aminotransferase (AST) level. The levels of aminotransferases may range from 10 times the upper limit of normal to more than 20 times the upper limit of normal. They increase rapidly and peak within 4-6 weeks of onset but generally return to normal within 1-2 months after the peak severity of the disease has passed. The serum alkaline phosphatase level may be normal or slightly increased (<3 times upper limit of normal). Serum bilirubin level usually ranges from 5-20 mg/dL, depending on the extent of hepatocyte damage. The patient may develop leukopenia with neutropenia or lymphopenia. Prolonged prothrombin time, decreased serum albumin, and very high bilirubin are signs of impending hepatic failure requiring referral to a liver transplantation center.
Perform blood cultures if the patient is febrile and hypotensive with an elevated white blood cell (WBC) count.
Acute hepatitis E virus (HEV) infection is diagnosed in immunocompetent individuals based on the detection of anti-HEV immunoglobulin M (IgM). The anti-HEV IgM usually starts rising 4 weeks after infection and remains detectable for 2 months after the onset of illness.
The test for the presence of anti-HEV IgM is performed by detection of specific IgM antibodies directed against a range of recombinant viral antigens by enzyme immunoassay or rapid immunochromatography kits. However, comparative studies show that these tests differ substantially in their accuracy. Therefore, users should ensure that a test is used that has been validated in their population. (34) Confirmation of acute cases detected in this way is either by molecular techniques, detecting rising reactivity in a specific immunoglobulin G (IgG) assay, or positivity in immunoblot IgM assays.
Detection of elevated reactivity in a specific IgG assay indicates the presence of acute hepatitis E. The worldwide population seroprevalence of HEV IgG ranges between 5% and 50%.However, the determination of immunity or previous exposure to HEV by detection of IgG antibodies is problematic. Available enzyme immunoassays use different antigens and vary in their effectiveness. The detection cutoff for some commercial assays may be close to the protective antibody concentration; therefore, they might not reliably detect protective concentrations of anti-HEV IgG.