Diagnosing viral hepatitis can be a complex process but it is important for civil society to understand the basic process so that they can work with governments and partners to ensure that those in need of testing have access to it. This page explains the ways in which viral hepatitis is diagnosed, with up to date information on the latest testing information.
Types of tests
|Type of assay||Characteristics|
|Rapid diagnostic test (RDT) ||-single use disposable assays
-do not require investment in laboratory equipment
-generally require no additional reagents except those supplied in the test kit
-good sensitivity and specificity
-read visually and give simple qualitative result in under 30 minutes
-easy to use and can be performed by trained lay providers or health care professionals
-used in decentralised settings, low resource settings and outreach programmes
-most are performed with capillary whole blood which is collected by a finger-stick procedure using a lancet but some use oral fluid
-generally not suitable for testing large numbers of blood samples; the reading of results is dependent on subjective evaluation and no permanent record of the original test results can be kept
|Laboratory based enzyme immunoassays (EIAs) – also known as an ELISA test ||high sensitivity and specificity
-best suited for and most cost-effective in settings with a high throughput of specimens (in excess of 40 a day)
-require infrastructure (electricity, cold storage, climate-controlled rooms) and skilled staff and so are meant for laboratory or facility based testing rather than for use in the community
-typically only used with serum or plasma specimens, meaning phlebotomy is required to collect an appropriate specimen
-longer time for results
Sensitivity – the ability of a test/assay to correctly identify those with the infection or disease (i.e. true positives/true positives and false negatives)
Specificity – the ability of a test/assay to correctly identify the absence of a disease (i.e. true negatives/true negatives and false positives)
The quality of the tests is highly important and selection of tests by national governments or other implementing partners should include consideration of stringent regulatory assessment, such as by the WHO prequalification programme or any of the founding members of the Global Harmonization Task Force:
- European Union
- US Food and Drug Administration
- Health Canada
- Therapeutic Goods Administration, Australia
- Japan Ministry of Health Labour and Welfare
It is important to note that regulatory assessment by any of the above country/regional authorities is specific to that country/region only and so may not mean that the test should/could be used in other countries/settings. All countries have their own registration mechanisms and diagnostics are required to be registered before they can be used within the country.
Many low and middle income countries use the WHO lists of prequalified products to guide their national procurement of diagnostics and/or facilitate national registration.
A list of WHO prequalified diagnostic tests for hepatitis B and hepatitis C along with those tests that have received stringent regulatory approval can be found here.
Diagnostic tests for hepatitis B and hepatitis C must be affordable, feasible and of good quality. They also need to have good sensitivity and specificity to ensure that there are not an unacceptable number of false positives or negatives.
Hepatitis C example costs
The highest prices for the HCV diagnostic package – initial screening, confirmatory testing, genotyping (should not be used), liver staging – are often found in the poorest countries. With these costs now often greater than the cost of the treatment. The below link shows the availability and pricing of viral load tests globally.
The cost of a test is made up of the below inputs:
- reagents and consumables*
- instrumentation/equipment (or reagent rental*)
- customs and taxes
- distributor margin
- personnel (including staff training)
- service and maintenance
- waste disposal
- external quality assurance
- results delivery
- other laboratory overheads
- profit margin.
*Reagent rental: equipment is placed free of charge in exchange for a guaranteed volume of reagent purchases (these are the cartridges). Some diagnostic companies add USD$1 to the cost of the cartridge under these schemes.
Manufacturers can offer different pricing mechanisms for tests:
Bundled pricing: volume based prices are set across a range of polyvalent tests (test for multiple disease types) rather than vertical pricing alone. This is generally limited to virological tests only and so excludes TB where common instrumentation, such as the Cepheid GeneXpert machine, could be valuable.
Preferential pricing: Lower pricing is given to certain countries but this is usually restricted to high burden and/or low-income countries and so a number of low and middle-income countries are excluded.
WHO guidance on who to test for chronic hepatitis C infection
|Focussed testing in most affected populations ||Adults and adolescents from populations most at-risk for hepatitis C (i.e. PWID, MSM, prisoners, sex workers, HIV co-infected, health care workers)
-Adults, adolescents and children who present with clinical symptoms that could be caused by chronic hepatitis C
|General population testing||In settings with a ≥2% or ≥5%4 HCV antibody seroprevalence in the general population,|
|Birth cohort testing||Birth cohorts of older persons who are at higher risk of infection (often due to unsafe medical practices when they were younger)
WHO guidance on who to test for chronic hepatitis B infection
|General population testing||Where seroprevalence is ≥2% or ≥5% in the general population.
Note: studiesin The Gambia have found that screening and treating the general population for hepatitis B can be cost-effective.
|Routine testing in pregnant women||Where seroprevalence is ≥2% or ≥5% in the general population.
Partners of pregnant women in antenatal settings should also be offered HBV testing.
|Focussed testing in most affected populations||-Adults and adolescents from populations most at-risk for hepatitis B (i.e. migrants, prisoners, sex workers, HIV co-infected)
-Adults, adolescents and children who present with clinical symptoms that could be caused by chronic hepatitis B
-Sexual partners, children, family members and close household contacts of those with hepatitis B
|Blood donors||In all settings, screening of blood donors should be mandatory with linkage to care, counselling and treatment for those who test positive|
Any screening activities should follow the 5 C’s of testing as set out by WHO:
- Correct test results
- Connection (linkage to prevention, treatment and care services)
Civil society and the affected community should be central to any screening activities and are critical to their success, both in the general population and at-risk groups. See our case studies for examples of the different ways that civil society and the affected community have enhanced screening activities.
ALT: this is an enzyme found in your liver. ALT is released to your bloodstream when your liver is damaged so a blood test checking for ALT levels can look for signs of liver disease.
Antibodies: are proteins made by a person’s immune system as part of your body’s response to neutralise pathogens such as bacteria and viruses.
APRI: is an index for estimating hepatic fibrosis based on a formula derived from aspartate aminotransferase (AST) which is another enzyme found in the liver, and platelet concentrations.
Assay: an investigative procedure for qualitatively assessing or quantitatively measuring the presence, amount or functional activity of a target.
Capillary blood sampling: taken from a finger prick. Depending on the test, it can be done by a health care professional or lay provider.
Dried Blood Spot (DBS) sampling: this form of testing requires a drop of blood on filter paper which can be transported from remote areas to a laboratory by standard means.
FIB-4: fibrosis 4 score.
Fibroscan: a technique to measure liver stiffness using sound waves performed much like an ultrasound (non-invasive).
HCV RNA: HCV viral genomes that can be detected and quantified in serum by nucleic acid testing (NAT)
Hepatitis B surface antigen (HBsAg): this tests for the presence of the virus. A positive test means that the person is infected with hepatitis B, which can be an ‘acute’ or ‘chronic’ infection.
Hepatitis B surface antibody (anti-HBs or HBsAb): a positive test indicates the person has successfully responded to the hepatitis B vaccine or has recovered from an acute hepatitis B infection. This means you are immune to hepatitis B and are not contagious.
Hepatitis B core antibody (anti-HBc or HBcAb): a positive test indicates a past or present infection and the interpretation of the results depends on the results of the other two tests.
Hepatitis C core antigen: is a viral protein that is part of the hepatitis C virus. It can usually be found in bloodstream two weeks after infection.
Reagents: chemical ingredients that are added to test a reaction
Serological tests/assays: are usually used as the first line of a testing strategy because of their relatively low cost. They are used to rule in all individuals who may potentially be infected. They detect the host immune response (antibodies) or a viral antigen. They can take the form of rapid diagnostic tests or laboratory based enzyme immunoassays.
Venous blood test: drawn from the vain by a trained health care professional.
Virological testing: using nucleic acid testing (NAT) technologies these are used to detect the presence of the virus (RNA or DNA), determine if the infection is active and if the individual would benefit from antiviral treatment. It is also used to confirm virological cure (HCV) or effective suppression (HBV).
WHO pre-qualification: http://www.who.int/diagnostics_laboratory/evaluations/PQ_list/en/
Overview of the WHO prequalification of in vitro diagnostics assessment: https://apps.who.int/iris/bitstream/handle/10665/259403/WHO-EMP-RHT-PQT-2017.02-eng.pdf;jsessionid=387D24F53BDCAA88F4DBA8BFD1B8DBF1?sequence=1
Lancet commission: https://www.thelancet.com/pdfs/journals/langas/PIIS2468-1253(18)30270-X.pdf
TAG Hepatitis C Diagnostic Factsheet: http://www.treatmentactiongroup.org/sites/default/files/201512/Diagnostics_0.pdf
TAG Pipeline Report on Hepatitis C Diagnostics: http://www.treatmentactiongroup.org/sites/default/files/pipeline_hcv_diagnostics_2019.pdf