Diagnosis of hepatitis B virus infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
The diagnosis of hepatitis B virus (HBV) infection was revolutionized by the discovery of Australia antigen, now called hepatitis B surface antigen (HBsAg). During the ensuing two decades, serologic assays were established for HBsAg and other HBV antigens and antibodies. Advances in molecular biology techniques led to the development of hybridization and polymerase chain reaction (PCR) assays for direct determination of hepatitis B virus DNA (HBV DNA). The diagnosis of HBV infection can also be made by the detection of HBsAg or hepatitis B core antigen (HBcAg) in liver tissues by immunohistochemical staining and of HBV DNA by Southern hybridization, in-situ hybridization, or PCR.
This topic review will focus on the changes in hepatitis B antigens, antibodies, and DNA levels that occur during acute and chronic infection and how these tests can be used clinically. A diagnostic algorithm will be presented for using these tests to diagnose acute hepatitis, past infection, and chronic infection.
WHO SHOULD BE TESTED OR SCREENED
We test for hepatitis B virus infection using HBsAg, hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) in certain groups of patients (table 1). The interpretation of positive serologic test results is described below. (See 'Diagnostic algorithms' below.)
We evaluate the following groups of patients for HBV, regardless of their vaccination history:
●Individuals who have signs and symptoms of acute hepatitis (see "Clinical manifestations and natural history of hepatitis B virus infection")
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- Chang MH, Hwang LY, Hsu HC, et al. Prospective study of asymptomatic HBsAg carrier children infected in the perinatal period: clinical and liver histologic studies. Hepatology 1988; 8:374.
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- Lok AS, Chung HT, Liu VW, Ma OC. Long-term follow-up of chronic hepatitis B patients treated with interferon alfa. Gastroenterology 1993; 105:1833.
- Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 2002; 36:1408.
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- Martinot-Peignoux M, Boyer N, Colombat M, et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol 2002; 36:543.
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- Wright TL, Mamish D, Combs C, et al. Hepatitis B virus and apparent fulminant non-A, non-B hepatitis. Lancet 1992; 339:952.
- Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45:507.
- Chan HL, Thompson A, Martinot-Peignoux M, et al. Hepatitis B surface antigen quantification: why and how to use it in 2011 - a core group report. J Hepatol 2011; 55:1121.
- Conjeevaram HS, Lok AS. Occult hepatitis B virus infection: a hidden menace? Hepatology 2001; 34:204.
- Bréchot C, Thiers V, Kremsdorf D, et al. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"? Hepatology 2001; 34:194.
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- Chaudhuri V, Tayal R, Nayak B, et al. Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology 2004; 127:1356.
- WHO SHOULD BE TESTED OR SCREENED
- SEROLOGIC MARKERS
- Hepatitis B surface antigen and antibody
- Hepatitis B core antigen and antibody
- - Isolated anti-HBc
- Hepatitis B e antigen and antibody
- SERUM HBV DNA ASSAYS
- Clinical use
- DIAGNOSTIC ALGORITHMS
- Acute hepatitis
- Past HBV infection
- Chronic HBV infection
- Occult HBV infection
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS