Hepatitis B - Laboratory diagnosis & Prophylaxis

 Laboratory diagnosis

 
HBsAg first appears in the blood during the incubation period, while the virus is actively 'replicating' in liver cells. The antigen is produced in vast excess - it is associated with new infectious virus particles as well as occurs in the serum as small non-infectious spherical and filamentous forms.

In acute infection, the HBsAg usually disappears within 3 months of onset. 

The HBeAg and HBV DNA can also be detected in blood while the virus is actively replicating in the liver . Symptoms usually appear as the concentrations of bilirubin, alanine aminotransferase and each of the major viral components peak in the serum. These events coincide with the first appearance of antibodies to HBV proteins

Antibody to HBcAg (anti-HBc) rises first. As a generalisation, the detection of IgM antibody specific to the hepatitis B core is the primary indicator of acute infection. It usually appears at or just before the onset of symptoms and remains detectable for at least 6 months. The IgG component of anti-HBc usually persists for life. 

Anti-HBe is the second antibody to appear and is associated with the rapid clearance of HBeAg. Later, anti-HBe declines and persists for only a few months or years if there is no active viral replication.

The antibody to HBsAg, anti-HBs, may not become detectable for 3-6 months after acute infection. It is associated with resolution of the illness. This antibody is recognised as the marker of immunity to HBV.

Detection of HBsAg + IgM HBcAg (anti-HBc) -recent/acute infection

Detection of HBsAg + IgG HBcAg (anti-HBc) -remote infection

Detection of HbeAg - High infectivity

Nondetection of HbeAg-low infectivity

Primary & secondary tests to diagnose/monitor hepatitis B virus (HBV) infection

	Marker	Incubation period	Acute infection	Past/resolved infection	Chronic infection	Vaccination
For diagnosis and monitoring
	HBsAg	±	+	–	+	–*
	Anti-HBs	–	–	+	–	+
	Anti-HBc- Total	–	±	+	+	–
	Anti-HBc- IgM	–	+	–	±†	–
	HBeAg	±	+	–	±	–
	Anti-HBe	–	–	±	± ‡	–
	HBV-DNA	±	+	±	+	–

^*Recent HBV vaccination within one to two weeks can lead to a false-positive test. The vaccine antigen can be detected at low levels;

^†May be positive in chronically infected individuals;

^‡Patients with chronic HBV infection usually have detectable Hepatitis B e antigen (HBeAg) or antibody to hepatitis B e protein (anti-HBe). Rarely, both HBeAg and anti-HBe can be detected simultaneously;

Interpretation of HBV Immunologic Markers

Markers				Interpretation
HBsAg*	HBcAb†	HBsAb‡
–	–	–	HBV infection
–	–	+	Immune because of vaccination
–	+	+	Immune because of natural HBV infection
+	+	–	Acute or chronic HBV infection
–	+	–	Interpretation unclear; four possibilities: l  Resolved HBV infection (most common) l  False-positive HBcAb l  “Low-level” chronic HBV infection l  Resolving acute HBV infection

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HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; + = positive test result; – = negative test result.

*— The presence of HBsAg indicates that the person is infectious.

†—HBcAb appears at the onset of acute HBV infection. Presence may also indicate chronic HBV infection or a false-positive test.

‡—The presence of HBsAb indicates recovery and immunity from HBV infection or successful immunization against HBV.

A recently infected chronic carrier will show evidence of ongoing viral replication in liver cells. HBeAg and HBV DNA can be detected in blood for months or years after acute infection.

Treatment

No specific antiviral treatment  for acute HBV infection. The main treatment is symptom relief.  Special consideration should be given to any medications that a patient takes to see the effect it may have on an impaired liver.

Interferon alpha alone or in combination with other antiviral agents such as lamivudine or famciclovir is useful in treating chronic hepatitis.  There is no treatment for carrier state though some show spontaneous resolution. 

Patients should avoid alcohol and cigarettes which can aggravate the liver.  

The only safe and effective measure for prevention is universal active immunisation. In 1992, WHO has recommended the integration of Hepatitis B vaccine into the immunisation programmes of all nations. India is lagging behind due to the high cost of imported vaccine. Development of low cost vaccine in India should help include this in national immunisation schedule.