Hepatitis B laboratory tests

Hepatitis Main Page
Hepatitis B
Home
Patient Information
Overview
Historical Perspective
Pathophysiology
Causes
Differentiating Hepatitis B from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
CT
MRI
Ultrasound
Treatment
Medical Therapy
Surgery
Primary Prevention
Hepatitis B Vaccination
Hepatitis B Vertical transmission
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Hepatitis B laboratory tests On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Hepatitis B laboratory tests All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Hepatitis B laboratory tests
CDC on Hepatitis B laboratory tests
Hepatitis B laboratory tests in the news
Blogs on Hepatitis B laboratory tests
Directions to Hospitals Treating Hepatitis B
Risk calculators and risk factors for Hepatitis B laboratory tests

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Laboratory Findings

Diagnosis of hepatitis is made by biochemical assessment of liver function. Initial laboratory evaluation should include:

• Total and direct bilirubin
• ALT
• AST
• Alkaline phosphatase
• Prothrombin time
• Total protein
• Albumin
• Globulin
• Complete blood count
• Coagulation studies

Diagnosis is confirmed by demonstration in sera of specific antigens and/or antibodies. Three clinical useful antigen-antibody systems have been identified for hepatitis B:

• Hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs)
• Antibody (anti-HBc IgM and anti-HBc IgG) to hepatitis B core antigen (HBcAg)
• Hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe)

Serological markers may vary throughout the course of the disease:

Hepatitis B diagnosis Adapted from World Health Organization

Very early in the incubation period, pre-S1 and pre-S2 antigens are present. They are never detected in the absence of HBsAg. Hepatitis B virions, HBV DNA, DNA polymerase, and HBeAg are then also detected. The presence of HBeAg is associated with relatively high infectivity and severity of disease.

Anti-HBc is the first antibody to appear. Demonstration of anti-HBc in serum indicates HBV infection, current or past. IgM anti-HBc is present in high titre during acute infection and usually disappears within 6 months, although it can persist in some cases of chronic hepatitis. This test may therefore reliably diagnose acute HBV infection. IgG anti-HBc generally remains detectable for a lifetime.

Anti-HBe appears after anti-HBc and its presence correlates to a decreased infectivity. Anti-HBe replaces HBeAg in the resolution of the disease.

The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or HBcAg. During this 'window' in which the host remains infected but is successfully clearing the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.

Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication.

If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen, (anti-HBs and anti HBc IgG). A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.

Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase levels and inflammation of the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others.

More recently, PCR tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens. These tests are called viral loads and are used to assess a person's infection status and to monitor treatment.

The original assays for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex. The table below is organized chronologically, from top to bottom:

Antigens	Antibodies
The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection with this virus; however, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host.	If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by antibodies to the hepatitis B surface antigen (anti-HBs).
The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or HBcAg	During this 'window' in which the host remains infected but is successfully clearing the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IGM) may be the only serologic evidence of disease.
Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication; however, some variants of the hepatitis B virus do not produce the 'e' antigen at all, so this rule does not always hold true.	During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise immediately afterward. This conversion is usually associated with a dramatic decline in viral replication.

A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously. A number of persons who are positive for HBsAg may have very little viral multiplication, and hence may be at little risk of long-term complications or of transmitting infection to others.

More recently, PCR tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens. These tests are useful to assess a person's infection status and to monitor treatment.

Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.

Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person

Recommendations for Monitoring Patients with Chronic HBV Infection: AASLD Practice Guidelines 2009

Class I

"1. HBeAg-positive and HBeAg-negative patients who meet criteria for chronic hepatitis B should be evaluated for treatment."

Class III

"2. HBeAg-positive patients: HBeAg-positive patients with persistently normal ALT should be tested for ALT at 3-6 month intervals. ALT along with HBV DNA should be tested more often when ALT levels become elevated. HBeAg status should be checked every 6-12 months. Patients who remain HBeAg positive with HBV DNA levels >20,000 IU/mL after a 3-6 month period of elevated ALT levels between 1-2 ULN, or who remain HBeAg positive with HBV DNA levels >20,000 IU/mL and are >40 years old, should be considered for liver biopsy, and treatment should be considered if biopsy shows moderate/severe inflammation or significant fibrosis. Patients who remain HBeAg positive with HBV DNA levels >20,000 IU/mL after a 3-6 month period of elevated ALT levels >2 ULN should be considered for treatment."

Class III

"3. HBeAg-negative patients: HBeAg-negative patients with normal ALT and HBV DNA <2,000 IU/mL should be tested for ALT every 3 months during the first year to verify that they are truly in the "inactive carrier state" and then every 6-12 months. Tests for HBV DNA and more frequent monitoring should be performed if ALT or AST increases above the normal limit."