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Who to test and how to test for chronic hepatitis C infection – 2016 WHO testing guidance for low- and middle-income countries

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Summary

Testing and diagnosis of hepatitis C virus (HCV) infection is the gateway for access to both treatment and prevention services, and crucial for an effective hepatitis epidemic response. In contrast to HIV, a systematic approach to hepatitis C testing has been fragmented and limited to a few countries, and there remains a large burden of undiagnosed cases globally. Key challenges in the current hepatitis testing response, include lack of simple, reliable, and low cost diagnostic tests, laboratory capacity, and testing facilities; inadequate data to guide country-specific hepatitis testing approaches and who to test; stigmatization and social marginalization of some groups with or at risk of viral hepatitis; and lack of international or national guidelines on hepatitis testing for resource-limited settings.

New tools to support the hepatitis global response include the 2016 Global Hepatitis Health Sector Strategy which include targets for testing and diagnosis, and World Health Organization (WHO) 2016 hepatitis testing guidelines for adults, adolescents, and children in low- and middle-income countries. The testing guidance complements recent published WHO guidance on the prevention, care and treatment of chronic hepatitis C and hepatitis B infection.

These testing guidelines outline the public health approach to strengthening and expanding current testing practices for HCV and HBV and address what serological and virological assays to use, and who to test, as well as interventions to promote linkage to prevention and care after testing. They are intended for use across all age groups and populations. See boxes for key recommendations.

Future directions and innovations in viral hepatitis testing include use of point-of-care assays for nucleic acid testing (NAT) and core antigen; validation of dried blood spots specimens with different commercial serological and NAT assays; multiplex and polyvalent platforms for integrated testing of HIV, HBV and HCV; and potential for self-testing.

Section snippets

High burden of undiagnosed infection and late diagnosis

Globally, it is estimated that 110 million people have serological evidence of current or past hepatitis C virus (HCV) infection and 80 million have chronic viraemic infection [1]. HCV infection is also a major cause of chronic liver disease (cirrhosis and hepatocellular carcinoma [HCC]) resulting in an estimated 703,800 deaths annually, and accounting for one third (34,500) of the total HCC mortality [2]. The burden of HCV remains disproportionately high in low- and middle-income countries

Goals of testing

Testing and diagnosis of hepatitis C infection is the gateway for access to both prevention as well as care and treatment services (Fig. 1), and is a crucial component of an effective response to the hepatitis C epidemic. The primary goals of diagnostic testing are to identify and link infected individuals, their partners and families to appropriate care and treatment for those in need with the direct-acting curative antiviral therapy, to reduce progression of liver disease and

The global response: WHO global strategy on hepatitis and testing targets

In order to overcome these challenges, and substantially increase awareness of hepatitis status and earlier diagnosis there is a need to provide services that can reach those populations most affected; well-functioning laboratories to ensure high-quality testing and treatment monitoring; a secure supply of quality-assured affordable diagnostics; an appropriately trained health workforce; and active involvement of affected communities.

In 2010 and 2014, two World Health Assembly resolutions

Distinctive features of WHO guidelines

Currently, there are few evidence-based viral hepatitis testing guidelines for LMICs. Existing national guidelines from high-income settings mainly recommend a focused/targeted risk factor-based testing for those with high-risk behaviours, exposures and other conditions. These include: PWID, MSM, HIV-positive persons, family members and household contacts of persons with hepatitis C, those undergoing renal dialysis, healthcare workers and persons with liver disease of unclear aetiology [13],

Learning from the global scale-up of HIV testing

Over the past 30 years there has been a progressive increase in uptake and coverage of HIV testing and an evolution in testing approaches, especially in recent years and in Sub-Saharan Africa [28]. The estimated percentage of people with HIV who were aware of their status has increased from 10% in 2005 to 54% in 2014 [29]. Much of this increase has been achieved as a result of an expansion of provider-initiated testing and counselling in clinical settings (particularly in antenatal and

WHO recommendations and rationale on who to test and how to test for chronic hepatitis C infection [34]

The scope of recommendations in the 2016 WHO guidelines on hepatitis B and C testing includes [34]: who to test for chronic hepatitis C infection (testing approaches); how to test for chronic hepatitis C infection (testing strategies); how to confirm viraemic HCV infection; how to assess response to antiviral treatment; use of dried blood spot (DBS) specimens for serology and nucleic acid testing (NAT) testing for HCV; and Interventions to promote uptake of testing and linkage to care. Table 2

Epidemic profiles, Testing approaches and service delivery options

HCV epidemics around the world are heterogeneous but are largely represented by mixtures of three main epidemic patterns for which specific testing approaches may be appropriate (Table 3). Hepatitis C testing can be undertaken in different populations and settings as part of focused testing approach in high-risk populations, or in the general population or birth cohort. These testing approaches can be offered and delivered using both health facility and/or community-based testing services.

Background

Diagnosis of HCV infection currently consists of initial screening for evidence of past or current HCV infection with a serological assay that detects hepatitis C antibody, followed by nucleic acid testing (NAT) technologies for HCV RNA (either quantitative or qualitative) or HCV (p22) core antigen (HCVcAg) to confirm the presence of HCV viraemia. Serological assays are based on the immunoassay principle and are available in the form of RDTs or laboratory-based enzyme-immunoassays (EIAs),

Background

Both quantitative and qualitative methods are available for the detection of viraemic HCV infection, although there has been limited comparison of the two methods. Quantitative NAT has been widely used for measuring viral load and identifying those in need of treatment, as well as assessing treatment response [18], [106]. There are currently five quantitative HCV RNA (viral load) assays that are commercially available with another two in the pipeline [106]. Qualitative NAT allows for rapid and

Background

Detection of HCV viraemia is important to assess the response to treatment. Prior to the introduction of curative oral DAA treatment regimens, treatment with interferon-based regimens required frequent monitoring of HCV viral load levels during therapy to decide whether treatment should be stopped, or treatment duration could be shortened based on a rapid reduction in viral load. These multiple assessments are less relevant with the newer DAAs because of the relative infrequency of viral

Background

Dried blood spot sampling may facilitates access to serological and NAT for hepatitis B and C, as well as other infectious diseases in remote and under resourced regions with poor access to laboratory services.

Significant scale-up in access to HCV testing and treatment will require further simplification of the process of diagnosis and monitoring, and methods to facilitate access to testing, especially in decentralised settings. DBS sampling is an alternative collection method for obtaining a

Point-of-care testing

The development of reliable, practical and affordable point-of-care tests will be crucial for expanding hepatitis testing services, especially in community-based settings, where there are challenges with cost, transport and venepuncture requirements [106]. Currently, although there are many RDT brands available, of the three HCV antibody serological assays that have been pre-qualified by WHO, two are laboratory-based serological tests.

NAT assays to detect HCV RNA that may be used at or near the

Acknowledgements

Guidelines Development Group

Many professionals from a range of backgrounds and specialties have contributed to the development of this guidance. WHO is sincerely grateful for their time and support. The following experts served on the Guidelines Development Group: Jacinto Amandua (Ministry of Health, Uganda); Isabelle Andrieux- Meyer (Médecins Sans Frontières, Geneva, Switzerland); Manal Hamdy El-Sayed (Egypt National Hepatitis Committee); Charles Gore (World Hepatitis Alliance, London, UK);

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    © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.