18.1. Principles for testing in all populations

• Hepatitis testing must emphasize the WHO 5 “Cs”. Mandatory, compulsory or coercive testing is never appropriate (see Chapter 16).
• All sites that provide hepatitis testing should have SOPs and ethical codes of conduct. They should protect client information and confidentiality, and should employ trained and supervised health workers (including lay providers).
• All HBV and HCV testing should follow WHO testing strategies and a validated national testing algorithm. Hepatitis testing should have appropriate QA and quality improvement (QI) mechanisms in place.
• Testing should be part of a care pathway that includes access to prevention, treatment and vaccination services. All persons who test positive for HBV and HCV should be linked to hepatitis care and treatment services.
• Priority for testing is to diagnose the undiagnosed as well as to identify those both in greatest need of treatment and at greatest risk of transmitting infection.

18.2. Principles for testing in key and high-risk populations

In some countries, HIV, HBV and HCV infections occur predominantly in certain key or high-risk populations, often via common routes of transmission. Key populations include PWID, MSM, people in prisons and other closed settings, sex workers and transgender people. These populations not only have an increased risk of infection, but their behaviours are often stigmatized, discriminated and criminalized. In almost all countries and settings, hepatitis testing for these key and priority populations is inadequate, and access to prevention, care and treatment services remains low.

• Promotion of health equity and human rights in hepatitis B and C testing is critical, as many of the affected populations such as PWID, prisoners, MSM, and sex workers are those who are systematically excluded from access to testing, treatment and care. Expanded testing and access should be fair, equitable and voluntary, and provided in a supportive environment free of stigma and discrimination.
• Essential strategies to create an enabling environment for access to hepatitis testing and treatment in these populations include: supportive legislation, policy and financial commitment, such as decriminalization of behaviours of key populations; addressing stigma and discrimination and violence against people from key populations; and community empowerment. In prisons, this can also include addressing additional systemic barriers contributing to transmission of viral hepatitis and other infectious diseases, such as confined unhygienic living spaces, lack of access to clean drinking water and adequate nutrition (458).
• Testing in prisons. Prisons provide an opportunity to offer testing and treatment to marginalized populations that otherwise might have difficulties accessing care. However, there is a need to guard against the negative consequences of testing in prisons such as mandatory or coercive testing and segregation of prisoners. There are also often major challenges to continuity of care between prisons and the community. All people who test positive need to be linked to viral hepatitis care and treatment services on discharge.
• Provision of a comprehensive package of prevention and treatment interventions. The high prevalence of comorbidities (e.g. viral hepatitis/ HIV coinfection, TB, mental health issues and polydrug use) in PWID and other high-risk populations means that the provision of comprehensive prevention, treatment, care and social services is important. WHO has outlined a comprehensive set of interventions and approaches for PWID (140), prisoners (459), MSM and sex workers (27, 57). These include provision of condoms, STI screening, HBV vaccination, OST provision and needle-syringe programme (NSP), and referral for ART and antiviral therapy.
• Full HBV vaccination or adoption of a catch-up vaccination programme is recommended for certain populations at increased risk of HBV, including PWID, MSM (26), sex workers and prisoners, without the need for prior HBsAg testing.
• Provision of accessible testing and treatment services.
  • Integration of testing and service delivery. To facilitate access, testing in certain populations such as PWID should be integrated, where possible, with delivery of other harm-reduction or drug dependency services and HIV testing (460).
  • Training of health-care workers. In many settings, health-care workers lack experience or training on how to provide inclusive and non-judgemental testing, and there are reports of discrimination against high-risk populations. Countries should prioritize the training of health workers so that they can provide acceptable services, better understand the needs of these populations, and be familiar with local support and prevention services. Similarly, services for transgender persons should be welcoming, with staff who are respectful and sensitive to transgender issues, and are knowledgeable about transgender medical concerns, such as the integration of hormone therapy and hepatitis care.
• Testing and repeat testing. Testing should be offered to not only current injecting drug users but to all persons who have ever injected drugs. Repeat screening is required in PWID and other groups such as MSM at ongoing risk of infection with a negative test. The possibility of reinfection after spontaneous clearance or successful treatment should also be considered. Those who have been previously infected should be retested using RNA testing, as the antibody remains positive after the first infection.

18.3. Persons living with HIV

Concurrent infection with HIV usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, HCC and mortality (462–465). HIV-infected persons are therefore a priority group for early diagnosis of viral hepatitis coinfection, and provision of both ART and specific antiviral therapy.

18.4. Tuberculosis-infected populations

Certain groups, such as PWID and people in prisons who at increased risk of HCV and HBV infection, are also at risk of infection with TB, largely because they live in regions and/or settings (e.g. prisons or regions of the world) that are endemic for these infections (467, 468).

18.5. Migrant and mobile populations

In some low-prevalence HBV and HCV regions, such as North America, Europe and Australia, the prevalence of viral hepatitis infection among persons born in high- and intermediate-endemic countries is higher, and reflects that in their country of origin. In other settings, minority ethnic groups and other mobile populations such as migrant workers, refugees, asylum seekers, fisher folk and lorry drivers, are particularly vulnerable to HBV, HCV and HIV infection. All these groups can be hard to reach and have difficulty in accessing health care for HIV or hepatitis testing services because of stigma, language differences, discrimination and legal barriers (53). Displacement of populations through human trafficking may further complicate the provision of testing services (53).

18.6. Health-care workers

Due to the risks associated with occupational exposure to blood and body fluids, health-care workers are a population at risk for acquisition of both hepatitis B and C infection. Exposure to blood and bodily fluids can occur through needle-stick and other sharps injuries, contact with blood and bodily fluids through scratches, abrasions or burns on the skin as well as mucosal surfaces of the eyes, nose, or mouth through accidental splashes (68). However, the largest proportion of occupational transmission of viral hepatitis is due to percutaneous injury via needles during vascular access (66). The risk of HBV transmission with such exposure is estimated to be 6–30% and for HCV transmission around 1.8% (68).

18.7. Couples, partners, family members and household contacts

Testing of couples and partners, family members and household contacts of persons with CHB infection, may be an efficient and effective way of identifying additional people with HBV infection who can also benefit from treatment and monitoring. This may also enable adoption of prevention strategies by the couple or family members (e.g. HBV vaccination, condom use, safe injecting practices) (471). Although the risk of HCV transmission to household contacts and sexual partners among heterosexual and HIV-negative MSM partners is low, there is a small but increased risk among sexual partners of PWID and MSM who engage in high-risk sexual behaviours or are HIV positive. An increasing number of countries offer couples and partner HIV testing (471) in various settings, including ANC, community-based TB services, and HIV/ART clinics, and this can also inform the service delivery of partner testing for viral hepatitis.

18.8. Pregnant women

Hepatitis B infection. Universal HBV testing in pregnant women already occurs in many parts of the world, but remains suboptimal in resource-limited settings (157). Box 18.1 summarizes the existing WHO guidelines on HBV infection prevention in newborns (6), but the most important preventive strategy is to deliver the first dose of hepatitis B vaccine as soon as possible after birth, preferably within 24 hours followed by at least two timely subsequent doses. Recent studies have suggested that there may also be a role for antiviral therapy in the third trimester in HBV-infected pregnant women to further reduce the risk of MTCT (157, 472, 473).

Box 18.1

WHO recommendations on HBV prevention in newborns and children.

Hepatitis C infection. Although the risk of MTCT of HCV infection is much lower than that of HBV infection, perinatal transmission of HCV occurs in between 4% and 8% of births, but the risk is two to three times higher if the mother is coinfected with HIV (96). Although the costs of implementing HCV testing alongside HIV and HBV is likely to be low, there is currently no effective public health intervention to decrease the risk of MTCT of HCV infection. However, identifying pregnant women who are HCV positive allows avoidance of procedures that promote mixing of fetal and maternal blood (e.g. use of scalp electrodes, amniocentesis), and may thus decrease transmission risk (98). It can also help promote testing of the child at 18 months. Identifying and treating women of reproductive age before they become pregnant preferable, but if DAAs are found to be safe and effective for use in pregnancy, they will also contribute to the prevention of MTCT.

18.9. Children

There are significant gaps and missed opportunities for diagnosis and documenting the HBV and HCV status of children of HBV-positive parents or HCV-positive mothers.

Hepatitis B infection. In endemic countries, HBV- infection is predominantly transmitted perinatally or in early childhood. In some settings, up to 50% of childhood infections may be attributable to horizontal intrafamilial transmission. In non-endemic settings, most children with CHB are migrants or children of migrants from endemic countries. Box 18.1 summarizes the existing WHO guidelines on HBV infection prevention in newborns. Although 70–90% of children who are exposed perinatally will become chronically infected, HBV-related morbidity is low during childhood as they are generally in the immune-tolerant phase. Since there are also low curative rates with both long-term NA and IFN treatment, and concerns over long-term safety and risk of drug resistance, a conservative approach to antiviral therapy is indicated, unless there are other criteria for treatment, such as cirrhosis or evidence of severe ongoing necroinflammatory disease (6). Tenofovir is approved for use in adolescents and children above the age of 12 years for HBV treatment (and 3 years or older for HIV treatment), and entecavir above 2 years of age.

Hepatitis C infection. In countries where adults have a high prevalence of HCV infection, an increased prevalence in children is often observed. This rate is particularly high in those exposed to medical interventions and treated in hospitals (101). Children born to mothers with HCV infection, especially those who are HIV-coinfected, are also at risk (96–99), and MTCT is the most common cause of HCV infection in young children.

As with HBV infection, the progression of HCV liver disease is usually slow in infected children. None of the DAAs have yet been approved for use among children (data from ongoing clinical trials will provide the necessary safety and efficacy data for paediatric regulatory approval), and so the only approved treatment remains PEG-IFN/ribavirin. However, as DAAs offer the potential for curative treatment at an early stage before progression of liver disease in children, earlier HCV testing in infants and children will also become more important.

Implementation considerations

• Service delivery approaches to delivering testing to infants and children. Box 18.2 shows potential testing approaches to improve hepatitis case-finding among infants and children. Infants whose mothers have been diagnosed with HBV or HCV should be followed up and routinely offered testing, and those diagnosed with either should be regularly monitored for signs of liver disease so that treatment can be offered when necessary. In high-prevalence settings, testing of HBV- and HCV-exposed infants could be available through a variety of services – child health services, immunization clinics, under-5 clinics, malnutrition services, well-child services, services for hospitalized and all sick children, TB clinics, and services for orphans and vulnerable children. Follow up through the breastfeeding period is also important to be able to offer HBV testing and vaccination for infants born to mothers with CHB who did not receive the HBV birth-dose vaccination, and to ensure that all children are followed up to receive the recommended three doses of vaccine. However, many infants are lost to follow up, which makes additional paediatric case-finding important.
• Testing in infants and children under 18 months. Hepatitis B. Testing of exposed infants is problematic within the first six months of life, as HBsAg and HBV DNA may be inconsistently detectable in infected infants. Exposed infants should be tested for HBsAg at 12 months of age–CHB is diagnosed if there is persistence of HBsAg for six months or more (95). Hepatitis C. HCV infection in children under 18 months can be confirmed only by virological assays to detect HCV RNA, because transplacental maternal antibodies remain in the child's bloodstream up until 18 months of age, making test results from serology assays ambiguous.

Box 18.2

Potential testing approaches to improve hepatitis case-finding among infants and children.

18.10. Adolescents

In high HBV-or HCV-prevalence settings, two groups of adolescents (defined as 10–19 years of age) are at potential risk of HBV or HCV infection and may need access to testing. These include the following: (1) undiagnosed adolescents who were HBV exposed perinatally or in early childhood in highly endemic HBV settings, and who missed out on HBV vaccination. These adolescents need to be diagnosed and started on antiviral treatment if and when this is clinically indicated, or if negative, vaccinated for HBV. (2) Adolescents who acquire HBV or HCV sexually or through injecting drug use through sex with multiple partners, or with MSM. It is important that these adolescents receive targeted interventions to increase access to HIV and hepatitis testing (474).