Bibliographic information
GuidelineGuidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection.
Year of Publication2024
Issuing InstitutionWHO
Recommendation
New
Point-of-care (POC) HBV DNA assays: POC HBV DNA nucleic acid test (NAT) assays may be used as an alternative approach to laboratory based HBV DNA testing to assess HBV DNA level for treatment eligibility and to monitor treatment response
Recommended in favor
Conditional
Certainty of evidence
Low
Notes and Remarks
- Use of laboratory-based versus POC NAT testing platforms: The choice of whether to use POC NAT versus laboratory assays depends on a variety of factors, including cost and ease of use and the characteristics of the testing site, such as storage facilities, infrastructure, level of staff skills and cost. Although POC assays may promote the uptake of viral load testing and turnaround time, there are also many excellent examples of a centralized laboratorybased system being highly effective when supported by efficient sample transport and rapid electronic delivery of results (1).
- Reflex NAT after a positive serological result: WHO now recommends reflex HBV DNA testing for people with positive HBsAg as an additional strategy to promote uptake and reduce time to HBV DNA testing and treatment. This can be achieved either through laboratorybased reflex NAT using a sample already held in the laboratory or clinic-based reflex testing in a health facility with immediate sample collection for HBV DNA testing following a positive HBsAg RDT. • Multi-disease testing platform and diagnostic integration across programmes: The introduction of multi-disease testing platforms, using either high-throughput laboratorybased or POC devices, brings additional opportunity for integration that may further expand access and achieve significant system efficiency and cost savings. Countries with existing multi-disease platforms for HIV, TB, HCV and SARS-CoV-2 or those that are planning to introduce them can consider collaboration and optimization of diagnostic networks across programmes (9) and integrating platforms across disease areas (HIV, TB, COVID-19 and HCV) can improve the rational utilization of existing capacity and save costs.
- WHO prequalification: WHO recently extended the prequalification process to include quantitative HBV DNA, inviting manufacturers to submit applications (see the list of WHO prequalified hepatitis B assays). As suppliers receive WHO prequalification status, this will facilitate expansion of these tests into countries with a high burden of hepatitis B.
- HBV DNA units: Serum HBV DNA levels should be expressed in IU/mL to ensure comparability. Values given as copies/mL can be converted to IU/mL by dividing by a factor of 5 to approximate the conversion used in the most commonly used assays (10 000 copies/mL = 2000 IU/mL; 100 000 copies/mL = 20 000 IU/mL; 1 million copies/mL = 200 000 IU/mL). POC HBV DNA assay platforms
- Priority settings for placing HBV POC platforms are likely to be more remote locations that lack laboratory infrastructure or sample transport, where testing volumes are low or settings such as antenatal care clinics, especially if a population of pregnant women with a high prevalence of hepatitis B need access to HBV DNA to assess eligibility for antiviral prophylaxis or treatment (2). With low volumes (less than 20 samples a day), a 4-, 8- or 16-cartridge machine with two or three runs per day may be adequate to meet demand.
- The optimal placement of a POC instrument is where testing and treatment are at the same site: Using POC platforms may not achieve expected outcomes if other aspects of the care pathway require travel to another clinic for treatment, with associated transport and other costs. For HCV care, POC assays achieved the best results when they were placed at sites where HCV testing and treatment were available at the same site as a one-stop shop, integrated into existing care, especially for people who inject drugs at harm-reduction sites, among people living with HIV in ART clinics, among prisoners and in primary care. This may be less applicable to hepatitis B care, since many people may meet treatment eligibility without need for an HBV DNA assay. Operational considerations for using and maintaining POC assays
- POC testing requires strong decentralized systems (such as quality control, platform maintenance, supply chain, trained personnel, adequate maintenance and waste disposal) and should consider patient flow and how to optimize sample collection, sample processing and results return.
- Basic laboratory infrastructure includes a centrifuge, a POC device and laptop, an airconditioner for temperature control, a room with a door to minimize dust, clinical waste disposal bins and access to a sink with running water for basic laboratory cleaning and managing accidents. If electricity is unstable and interrupted, an online uninterruptible power supply and voltage stabilizer are required.
- Regular internal quality control and quality assurance checks can ensure appropriate use of the POC device and identify errors.
- Personnel training could include laboratory experience or specific skill training required for preparing plasma samples for a POC instrument: centrifuging and pipetting an exact sample amount.
- Annual calibration checks are required for the validity of the device warranty, and he service contract and warranty should include maintenance or replacements. • Storage and transport: some POC analysers require storage at 2–28°C, stable continuous electricity supply, no direct sunlight and an environment controlled to minimize dust and humidity.
- Transport and disposal: cartridges should be transported similar to storage conditions and disposed of using clinical waste disposal, ensuring that chemicals are not released into the environment (requiring high-temperature incineration if they contain guanidinium thiocyanate).