Hepatitis B Virus

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Hepatitis B Virus Testing Algorithm

Hepatitis Virus Screening Algorithm

Clinical Background

Hepatitis B (HBV) is a blood-borne virus and one of the most common infectious diseases in the world.

Epidemiology

Incidence - about 50,000/year in the U.S.
Transmission
- Parenteral
- Sexual
- Vertical perinatal
- Horizontal - from chronically infected person in a household

Organism

Eight HBV subgroups (A-H) based on genetic differences
Genotype may be associated with disease progression
Not directly cytotoxic to hepatocytes
Severity of injury is modulated by host immune responses

Risk Factors

Intravenous drug abusers
Multiple sex partners (more than 1 partner during the preceding 6 months)
Sexual transmission from HBV-positive partner
Infants of infected mothers
Persons infected with human immunodeficiency virus (HIV)
High rates of HBV infection continue to occur among Alaska Native and Pacific Islander children and among children residing in households of first-generation immigrants from countries where HBV infection is endemic
HIV infection

Clinical Presentation

Acute HBV
- Approximately 50% of the people who are infected will have symptoms which usually appear within 25 to 180 days following exposure
- The mildest attacks are asymptomatic and detectable only by an increase in serum transaminase levels
- Influenza-like symptoms - fatigue, malaise, fever
- Jaundice and gastrointestinal symptoms
- A few develop acute fulminant hepatic failure requiring transplantation

Chronic HBV

Phases of infection
- Immune tolerance
- Immune clearance
- Inactive carriers
- Reactivation
Infants and young children are at the greatest risk for becoming chronically infected if exposed to the hepatitis B virus
- 90% of exposed infants will develop chronic hepatitis
- 30% of exposed children ages 1-5 will develop chronic hepatitis
- Only 5% of exposed adults will develop chronic hepatitis
Most common findings are fatigue and modestly elevated transaminases
Patients may have systemic symptoms that are associated with the deposition of circulating hepatitis B antigen-antibody immune complexes such as arthritis, leukocytoclastic vasculitis, glomerulonephritis, cryoglobulinemia and generalized vasculitis
Long-term consequences include cirrhosis and hepatocellular carcinoma

Treatment

Current therapies are available
- May be curative or significantly reduce viral load in chronic hepatitis
- Reduces risk of hepatocellular carcinoma

Prevention

Vaccination is recommended for:
- Persons who reside in a community with an increased prevalence of infection
- Persons who will travel to a country with high prevalence rates
- Health care workers
- All neonates and children
- HIV positive patients
- Prisoners

See Also

Cirrhosis

Hemochromatosis

Hepatitis A Virus - HAV

Hepatitis C Virus - HCV

Hepatitis Delta Virus - HDV

Hepatitis, Acute

Hepatitis, Autoimmune - AIH

Hepatocellular Carcinoma

Liver Disease Evaluation

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Hepatitis B Virus Testing Algorithm

Hepatitis Virus Screening Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Hepatitis B Virus Surface Antigen with Reflex to Confirmation

ARUP #: 0020089

Methodology: Chemiluminescent Immunoassay

Use:

For acute onset of hepatitis, order along with HBV core IgM, HAV IgM and HCV antibodies to diagnose viral causative agent

Diagnose chronic hepatitis B, order along with HBV surface antibody and HBV core antibodies (total)

Limitations:

Follow-up:

Test name: Hepatitis B Virus Core Antibodies (Total)

ARUP #: 0020091

Methodology: Chemiluminescent Immunoassay

Use:

Diagnose chronic hepatitis B infection; order along with HBV surface antigen and HBV surface antibody

Limitations:

This assay tests for IgG and IgM antibodies but does not differentiate between them

Approximately 1% of blood donors will have a positive anti-HBc and negative HBsAg
These donors should be further evaluated by measuring anti-HBs; however, most of these donors will have a negative anti-HBs

Follow-up:

Test name: Hepatitis B Virus Surface Antibody

ARUP #: 0020090

Methodology: Chemiluminescent Immunoassay

Use:

Diagnose chronic hepatitis; order along with HBV surface antigen and HBV core antibodies (total)

Monitor hepatitis B therapy; order along with HBV DNA, HBV surface antigen, HBe antigen, and HBe antibody

Assess responsiveness to previous vaccination in health-care workers

Test name: Hepatitis B Virus Core Antibody, IgM

ARUP #: 0020092

Methodology: Chemiluminescent Immunoassay

Use:

For acute onset of hepatitis, order along with HBV surface antigen, HAV IgM and HCV antibodies to diagnose viral causative agent

Limitations:

Follow-up:

Test name: Hepatitis Be Virus Antigen

ARUP #: 0020094

Methodology: Enzyme Immunoassay

Use:

Monitor hepatitis B therapy; order along with HBV DNA, HBV surface antigen, HBV surface antibody and HBe antibody

Limitations:

Order only when a patient is known to be positive for HBV surface antigen

Follow-up:

Test name: Hepatitis Be Virus Antibody

ARUP #: 0020095

Methodology: Enzyme Immunoassay

Use:

Monitor hepatitis B therapy; order along with HBV DNA, HBV surface antigen, HBV surface antibody and HBe antibody

Limitations:

Follow-up:

Test name: Hepatitis B Virus DNA Ultrasensitive Quantitative Real-Time PCR

ARUP #: 0056025

Methodology: Real-Time Polymerase Chain Reaction

Use:

Monitor hepatitis B therapy; order along with HBV surface antigen, HBV surface antibody, HBe antigen and HBe antibody

Monitor patients who were infected with hepatitis B virus prior to liver transplantation

Limitations:

A result of less than 40 HBV IU/mL does not rule out the presence of PCR inhibitors in the patient specimen or HBV DNA concentrations below the limit of detection by the assay

Follow-up:

Test name: Immunohistochemistry Stain Offering

ARUP #: arup005

Methodology: Immunohistochemistry

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for HBcAg and HBsAg are available

Additional Tests Available

Test name: Hepatitis B Virus Surface Antigen, Confirmation

ARUP #: 0020128

Methodology: Chemiluminescent Immunoassay

Comments:

Test name: Hepatitis B Virus Panel, Chronic with Reflex to HBsAg Confirmation

ARUP #: 0020454

Methodology: Enzyme Immunoassay/Chemiluminescent Immunoassay

Comments:

Additional Information

Diagnosis of Acute HBV Infection
HBsAg	anti-HBc IgM	Interpretation
positive	positive	Acute HBV infection, follow to determine resolution
positive	negative	HBV infection (could be chronic), consider possibility of contamination
negative	positive	HBV infection, probably resolving
negative	negative	Not HBV infection, consider other forms of hepatitis (A, C, E), CMV, EBV and others

References

Guidelines

(1) Chronic hepatitis B. (2) Corrections to AASLD guidelines on chronic hepatitis B. American Association for the Study of Liver Diseases - Private Nonprofit Research Organization. 2001 Dec (revised 2007 Feb; addendum released 2007 Jun). Original guideline: 25 pages; Addendum: 1 page. NGC:005652

Hepatitis B virus. New York State Department of Health - State/Local Government Agency [U.S.]. 2003 Mar (revised 2004 Sep). 12 pages. NGC:004534

Screening for hepatitis B virus infection: recommendation statement. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2004 Feb 24). 4 pages. NGC:003453

General References

Bowden S. Serological and molecular diagnosis. Semin Liver Dis. 2006;26(2):97-103.

Chang MH. Hepatitis B virus infection. Semin Fetal Neonatal Med. 2007;12(3):160-167.

Dumas L, Vergani D, Mieli-Vergani G. Hepatitis B virus: something old, something new. J Pediatr Gastroenterol Nutr. 2007;44(1):14-17.

Hollinger FB. Hepatitis B virus genetic diversity and its impact on diagnostic assays. J Viral Hepat. 2007;14 Suppl 1:11-15.

Lai CL, Yuen MF. The natural history of chronic hepatitis B. J Viral Hepat. 2007;14 Suppl 1:6-10.

Morgan M, Park W, Keeffe EB. Diagnosis and treatment of chronic hepatitis B: an update. Minerva Gastroenterol Dietol. 2007;53(1):25-41.

O'Shea R. Chronic hepatitis B virus infection: issues in treatment. Cleve Clin J Med. 2007;74(8):557-560.

Safioleas M, Lygidakis NJ, Manti C. Hepatitis B today. Hepatogastroenterology. 2007;54(74):545-548.

Tan J, Lok AS. Update on viral hepatitis: 2006. Curr Opin Gastroenterol. 2007;23(3):263-267.

Thio CL. Diagnosis, diagnostic tests and monitoring of hepatitis B virus in monoinfected and HIV-coinfected patients. Antivir Ther. 2007;12 Suppl 3:H25-H31.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Konnick EQ, Erali M, Ashwood ER, Hillyard DR. Evaluation of the COBAS amplicor HBV monitor assay and comparison with the ultrasensitive HBV hybrid capture 2 assay for quantification of hepatitis B virus DNA. J Clin Microbiol. 2005;43(2):596-603.

La'ulu SL, Roberts WL. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am J Clin Pathol. 2006;125(5):748-751.

Medical Reviewers

Hillyard, David R., M.D. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Slev, Patricia , Ph.D. Assistant Medical Director, Hepatitis and Retrovirus Serology and Special Chemistry at ARUP Laboratories

Comprehensive Review: September 2008
Last Update: September 2008