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2.0 Diagnostic Strategies

Posted in: HBV

2.1 Types of hepatitis B diagnostic tests – also called in-vitro diagnostic devices

A range of serological and nucleic acid tests (NATs) are used for donor and diagnostic testing.

Table 1. Technology, purpose and categorisation of assays used for HBV testing.

Marker Abbreviations Purpose or uses Technology
Hepatitis B surface antigen (qualitative) HBsAg Donor testing – screening of blood and tissue donations Immunoassay
Diagnostic testing

Immunoassay

Hepatitis B surface antigen neutralisation   Confirmation of the presence of HBsAg Immunoassay
Hepatitis B surface antigen (quantitative) HBsAg Monitoring of therapy Immunoassay
Hepatitis B surface antibody anti-HBs or HBsAb Determining protective immunity* Immunoassay
Hepatitis B core total antibody anti-HBc or
HBcT or
HBcAb
As part of strategy to determine exposure to HBV Immunoassay
IgM to hepatitis B core antigen

anti-HBc IgM or
HBc IgM

As part of strategy to diagnose acute hepatitis B infection Immunoassay
Hepatitis B e antigen HBeAg Determining infectivity of a person with HBV infection and phase of the infection for clinical management Immunoassay
Hepatitis B e antibody anti-HBe or
HBeAb
Determining seroconversion from hepatitis B e antigen and phase of the infection for clinical management

Immunoassay

Hepatitis B DNA (qualitative) HBV DNA Donor testing – screening of blood and tissue donations

NAT

Hepatitis B DNA (quantitative) HBV DNA VL Monitoring and management- quantifies virus for clinical management Quantitative NAT (viral load)
Confirm the presence of circulating HBV
Determine the eligibility of a health care worker to perform exposure-prone procedures
Hepatitis B genotype / mutation**   Characterisation of virus for clinical management

Sequencing

Line probe

*anti-HBs levels fall over time and may become undetectable in people vaccinated years ago or in those who have cleared the virus. In the setting of normal immune function, these individuals are still regarded as having effective immunity. Where relevant, anti-HBc may provide evidence of past exposure when anti-HBs has become undetectable. Refer to the Australian Immunisation Handbook for further advice.HIV infected patients with low CD4 counts and a low anti-HBs despite vaccination are at risk of re-infection, as are people with end stage renal failure undergoing haemodialysis. Testing for reinfection would be as for diagnosis of acute HBV infection, although HBV DNA may be the preferred first investigation due to poor antibody responses.

**The above tests are rebatable under the conditions outlined in the Medicare Benefits Schedule, however hepatitis B genotype / mutation conferring resistance is not Medicare rebatable and a fee may be payable.

Tests for hepatitis B virus (HBV) must comply with the regulatory framework for in-vitro diagnostic medical devices (IVDs) under the Therapeutic Goods Act 1989 and subordinate legislation. Testing in laboratories must comply with standards specified by the National Association of Testing Authorities (NATA) and the National Pathology Accreditation Advisory Council (NPAAC)

(A) Donor Screening

Australian laboratories screening blood or tissue prior to transfusion or transplantation must test the donor’s serum or plasma for the presence of HBsAg. Blood donors and donors of most tissues are screened for the presence of HBV DNA using a NAT. IVDs used for donor screening must be intended for that purpose and be included on the Australian Register of Therapeutic Goods (ARTG) as a Class 4 IVD.

(B) Diagnostic Tests

Individuals suspected of exposure to HBV may be tested for a range of diagnostic markers depending on their clinical history, symptoms and previous test results.Examples of the common serological patterns observed in acute and chronic HBV infection are shown (see section 2.2). All assays intended by the manufacturer for the clinical diagnosis of HBV infection are Class 4 IVDs.

Common diagnostic testing strategies encompass:

  • diagnosis of acute infection (5% of notifications) – HBsAg, anti-HBc, anti-HBc IgM;
  • diagnosis of chronic HBV infection – HBsAg, anti-HBs, anti-HBc;
  • determination of protective immunity or its absence in at-risk groups – anti-HBs; (if anti-HBs is negative recommend HBsAg and anti-HBc to exclude undiagnosed infection or distant past infection);
  • antenatal – HBsAg; (if possible also perform anti-HBs, to assess the need for vaccination);
  • pre-operative/insurance screening– HBsAg;
  • investigation of degree of infectivity when HBsAg positive or the assessment of disease phase in a person with chronic hepatitis B– HBV DNA; anti-HBe, HBeAg;
  • monitoring of therapy – quantitative HBV DNA, HBsAg, HBeAg, anti-HBs, anti-HBe.

Note that there are three tests for hepatitis antibodies or antigens for the investigation of infectious causes of acute or chronic hepatitis (Medicare Benefit Schedule item 69481). Benefits for these tests are only payable if the request from the ordering practitioner identifies in writing that the patient is suspected of suffering from acute or chronic hepatitis, either by use of the provisional diagnosis or relevant clinical or laboratory information. More detail on HBV testing and the MBS are presented in section 12.0 of this Policy or from MBS online – http://www.mbsonline.gov.au/

(C) Rapid Tests for Use at Point of Care

HBsAg point-of-care (PoC) tests are available in other countries but there are no PoC tests for HBV currently approved by the Therapeutic Goods Administration (TGA) for inclusion on the ARTG. While there are settings where PoC testing would be useful (e.g. testing in remote communities and where there are barriers to accessing traditional health care), HBsAg PoC tests are known to have a lower analytical sensitivity compared to standard laboratory immunoassays and may be unable to detect low levels of HBsAg. Some people in the community may access self-administered PoC test from overseas. Therefore, where a person indicates they have received a positive or negative PoC test the result should be confirmed by standard HBV testing in a NATA certified diagnostic laboratory.

(D) Reference Tests

The presence of HBsAg detected by screening tests must be confirmed by HBV neutralisation testing as recommended by the manufacturer’s instructions and as approved by the TGA. Blood donors in Australia are screened using a multiplex NAT assay that detects HIV-1 RNA, HCV RNA and HBV DNA. Samples reactive on a NAT multiplex assay are further tested by individual discriminatory assays for HIV-1 RNA, HCV RNA and HBV DNA to determine which viral marker(s) are present in the sample.

(E) Hepatitis D Testing

Hepatitis D virus (HDV) is a satellite RNA virus dependent on HBsAg for its viral envelope and thus only infects individuals with active HBV infection. Infection with HDV can occur concurrently with an HBV infection (co-infection) or it may occur in a chronically infected HBV patient (superinfection). It is important to consider testing for HDV in all HBV infected patients as there is evidence this co-infection is substantially under-diagnosed in Australia.Particular situations which should prompt testing for HDV infection include those with a severe presenting illness (suggesting co-infection), a flare of more stable chronic HBV (superinfection) or if they are from a region where HDV infection has a high prevalence. Testing for HDV initially involves anti-HDV serology (both IgM and IgG antibodies can be requested). If the anti-HDV results are positive then HDV RNA should be requested. While HDV RNA assays are not commercially available, laboratories will refer HDV RNA requests to a specialist reference laboratory (note this test is not on the Medicare Benefit Schedule).

2.2 Diagnostic strategies for HBV

Suspected acute HBV

AcuteHBV flowchart

* Note that anti-HBc IgM can often be detected during an exacerbation of chronic hepatitis B infection. HBV is a notifiable disease and a positive result should be notified to the relevant Public Health Authority.

 

Suspected chronic HBVi

(click on picture to enlarge)CHB Flowchart wmall

 

  1. Write in lab request ‘testing for possible chronic HBV
  2. anti-HBs levels fall over time and may become undetectable in people vaccinated years ago or in those who have cleared the virus. These individuals are still regarded as having acquired immunity. Refer to The Australian Immunisation Handbook  for further advice
  3. Further testing is indicated in persons who may be in the window period before the development of any HBV serological markers. HBsAg is usually detected 6-12 weeks after exposure (in high-risk situations, consider post-exposure prophylaxis as appropriate)
  4. Note that there is some risk of HBV reactivation in the setting of intense immunosuppression 
  5. Consider family screening and contact tracing given possible exposure risks
  6. People at risk of already having advanced liver disease or liver cancer despite resolved HBV infection, which includes people from CALD backgrounds, people who acquired HBV infection perinatally or in early childhood, and people with other risk factors for liver disease, should be referred for assessment of liver fibrosis severity and further specialist management as required
  7. Consider passive transfer in patients who recently received plasma derived products eg. IV Immunoglobulin
  8. Lab report must either say positive or >10 mIU/mL
  9. HBV DNA viral load is NOT rebatable in patients who are HBsAg negative

 

 

 

 

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Development of this site and the 2014 and 2017 revisions of the testing policies was supported by: Australian Government Department of Health and Ageing