| How is hepatitis B diagnosed?
Hepatitis B is diagnosed from the results of specific hepatitis B virus blood tests (serologies) that reflect the various components of the hepatitis B virus. A discussion of each of the hepatitis B virus blood tests follows. These serological hepatitis B virus blood tests differ from the standard liver blood tests (such as the ALT and AST) that can become abnormal when the liver is damaged from whatever cause, including hepatitis B viral infection.
HBsAg and anti-HBs
The diagnosis of hepatitis B infection is made primarily by detecting the hepatitis B surface antigen (HBsAg) in the blood. The presence of HBsAg means that there is active hepatitis B viral infection and the absence of HBsAg means that there is no active hepatitis B viral infection. Following an exposure to hepatitis B virus, HBsAg becomes detectable in the blood within four weeks. In individuals who recover from acute hepatitis B viral infections, the elimination, or clearance, of HBsAg occurs within four months after the onset of symptoms. Chronic hepatitis B viral infection is defined as the persistence of HBsAg for more than six months.
After the HBsAg is eliminated from the body, the antibodies to HBsAg (anti-HBs) usually appear. These anti-HBs provide immunity to subsequent hepatitis B viral infection. Likewise, individuals who are successfully vaccinated against hepatitis B virus have measurable anti-HBs in the blood.
Anti-HBc
The hepatitis B core antigen can only be found in the liver and cannot be detected in the blood. The presence of large amounts of hepatitis B core antigen in the liver indicates an ongoing reproduction of the virus. This means that the virus is active. The antibody to hepatitis B core antigen, known as the hepatitis B core antibody (anti-HBc), however, is detectable in the blood. As a matter of fact, two types of anti-HBc antibodies (IgM and IgG) are produced.
IgM anti-HBc is a marker (indicator) for acute hepatitis B infection. The IgM anti-HBc is found in the blood during the acute infection and lasts for up to six months after the onset of symptoms. IgG anti-HBc develops during the course of the acute hepatitis B viral infection and persists for life, regardless of whether the individual recovers or develops the chronic infection. Accordingly, only the IgM type of anti-HBc can be specifically used to diagnose an acute hepatitis B viral infection. Moreover, determining just the total anti-HBc (without separating its two components) is not very helpful.
HBeAg, anti-HBe, and pre-core mutations
Hepatitis B e antigen (HBeAg) and its antibody, anti-HBe, are useful markers to determine the likelihood of spread of the virus (transmissibility) by persons affected with chronic hepatitis B viral infection. Detecting both HBeAg and anti-HBe in the blood is usually mutually exclusive. Accordingly, the presence of HBeAg means ongoing viral activity and the ability to infect others, whereas the presence of anti-HBe signifies a more inactive state of the virus and less risk of transmission.
In some individuals infected with hepatitis B virus, the genetic material for the virus has undergone a particular structural change, called a pre-core mutation. This mutation results in an inability of the hepatitis B virus to produce HBeAg, even though the virus is actively reproducing. This means that even though no HBeAg is detected in the blood of people with the mutation, the hepatitis B virus is still active in these persons and they can infect others.
Hepatitis B virus DNA
The most specific marker of hepatitis B virus reproduction is the measurement of hepatitis B virus DNA in the blood. You remember that DNA is the genetic material of hepatitis B virus. High levels of hepatitis B virus DNA indicate an ongoing reproduction of the virus and viral activity. Low or undetectable levels of hepatitis B virus DNA are associated with the inactive phase of hepatitis B viral infection. Several different laboratory tests (assays) are available to measure hepatitis B virus DNA.
The PCR (polymerase chain reaction) is the most sensitive method (assay) for determining the level of hepatitis B virus DNA. This means that the PCR is the best method for detecting minute amounts of the hepatitis B virus marker. This method works by amplifying the material that is being measured up to a billion times for its detection. The PCR method, therefore, can measure as few as 50 to 100 copies (particles) of hepatitis B virus per milliliter of blood. This test, however, is actually too sensitive for practical diagnostic use.
The purpose of measuring hepatitis B virus DNA usually is to determine whether the hepatitis B viral infection is active or inactive (quiescent). This distinction can be made based on the amount of hepatitis B virus DNA in the blood. High levels of DNA indicate an active infection, while low levels indicate a dormant, or inactive, infection. Thus, patients with dormant disease have about a million viral particles per milliliter of blood, whereas patients with active disease have several billion particles per milliliter. Therefore, anyone who is HBsAg positive, even if the hepatitis B viral infection is inactive, will have detectable levels of hepatitis B virus DNA by the PCR method because it is so sensitive.
For practical purposes, hepatitis B virus DNA can be measured using a so-called hybridization method (assay), which is a less sensitive test than the PCR. Unlike the PCR method, the hybridization assay measures the viral material without amplification. Accordingly, this test can detect hepatitis B virus DNA only when many viral particles are present in the blood, meaning that the infection is active. In other words, from a practical point of view, if hepatitis B virus DNA is detected with a hybridization assay, this means that the hepatitis B viral infection is active.
How are the hepatitis B virus blood tests interpreted?
Table 1 gives the diagnostic interpretations for various sets of results obtained with a battery of hepatitis B virus blood (serological) tests. Keep in mind, however, that the interpretation of the hepatitis B virus blood tests should always be made with knowledge of the patient's medical history, physical examination, and results of the standard liver blood tests that can indicate damage to the liver.
Table 1: Interpretation of hepatitis B virus blood (serological) tests (+ = positive and - = negative)
HBsAg Anti-HBs Anti-Hbc (total) Anti-HBc IgM HBeAg Anti-HBe HBV DNA Interpretation
+ - + + + + + Early phase of acute infection
+ - + + - + - Later phase of acute infection
- - + + - + - Later phase of acute infection
- + + - - - - Recovery with immunity
- + - - - - - Successfully vaccinated
+ - + - + - + Chronic infection with active reproduction
+ - + - - + - Chronic infection in the inactive phase
+ - + - - + + Chronic infection with active reproduction
- - + - - + or - - Recovery, False positive result, or Chronic infection
What is the role of a liver biopsy in chronic hepatitis B?
A liver biopsy is an important part of the work-up of a patient with chronic hepatitis B virus. This test is valuable because the small core of tissue taken from the liver is generally representative of the rest of the liver. Furthermore, a diagnosis of chronic hepatitis can usually be made from the biopsy. However, the type of chronic hepatitis (or the cirrhosis it causes), whether it be hepatitis B, C, or autoimmune hepatitis, cannot be determined definitively from the biopsy.
The patient's medical history, physical examination, standard liver blood tests, and hepatitis B virus blood tests (serologies), along with the liver biopsy, are all used to make the diagnosis of the specific type of chronic hepatitis. Still, the liver biopsy is the test that shows the amount of liver injury (inflammation) and scarring (fibrosis) in the chronic hepatitis or cirrhosis. The information obtained from the biopsy is then used to help determine the prognosis (course and outcome) of the disease as well as the need for anti-viral treatment.
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