This chapter addresses special considerations that apply to viral hepatitis testing in
certain priority and high-risk or key populations. This includes PWID; persons in
prisons or closed settings; MSM; sex workers; transgender people; persons living with
HIV; TB-infected populations; migrant and mobile populations; healthcare workers;
couples, partners and household contacts; pregnant women; children; and adolescents.
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.
Further reading
* Consolidated guidelines on HIV prevention, diagnosis, treatment
and care for key populations.
Geneva:
WHO; 2014 [PubMed: 25996019]
and update 2016 (25) describes
essential services for key populations and interventions to reduce barriers to
testing and linkage to care after testing. (http://www.who.int/hiv/pub/guidelines/keypopulations/en/)
* Integrating collaborative TB and HIV services within a
comprehensive package of care for people who inject drugs.
Geneva:
WHO; 2016
(461). (http://apps.who.int/iris/bitstream/10665/204484/l/9789241510226_eng.pdf?ua=1)
* Guidance on prevention of viral hepatitis B and C among people
who inject drugs. Geneva:
WHO
2012 (http://apps.who.int/iris/bitstream/10665/75357/1/9789241504041_eng.pdf?ua=1) [PubMed: 23805439]
(28)
* WHO, UNODC, UNAIDS
Technical guide for countries to set targets for universal access to
HIV prevention, treatment and care for injecting drug users
–2012 revision. Geneva:
WHO
2013 (http://www.who.int/hiv/pub/idu/targets_universal_access/en/,
accessed 08 July
2016) (140).
* UNODC, ILO, UNDP,
WHO, UNAIDS. HIV prevention,
treatment and care in prisons and other closed settings: a comprehensive
package of interventions.
Vienna:
UNODC; 2013 (http://www.
who.int/hiv/pub/prisons/interventions_package/en/,
accessed 08 July
2016) (459).
* Prevention and treatment of HIV and other sexually transmitted
infections for sex workers in low- and middle-income countries.
Geneva:
WHO; 2012. (https://www.unfpa.org/sites/default/files/pub-pdf/9789241504744_eng.pdf) [PubMed: 26131541]
(27).
* Implementing comprehensive HIV/STI programmes with sex workers:
practical approaches from collaborative interventions.
Geneva: World Health
Organization; 2013 (http://apps.who.int/iris/bitstream/10665/90000/1/9789241506182_eng.pdf)
(57).
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.
Implementation considerations
Comparable outcomes of DAA therapy have been seen in persons with
HIV coinfection as for those with HCV monoinfection, with
cure rates higher than 95%, even for those with prior HCV
treatment failure or advanced fibrosis (
5). Therefore, there is no longer a need to
consider HIV/HCV-coinfected patients as a special, difficult-to-treat
patient population.
HBV vaccination. The risk of HBV infection may be higher in
HIV-infected adults, and therefore all persons newly diagnosed with HIV
should be screened for HBsAg and anti-HBs to identify those with CHB,
and vaccinated if non-immune. Response to HBV vaccine may be lower in
HIV-infected persons especially those with a low CD4 count. A schedule
using four double (40 μg) doses of the vaccine provides a higher
protective anti-HBs titre than the regular three 20 μg dose
schedule (
466).
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).
Implementation considerations
Supporting intensified tuberculosis case-finding at testing
facilities. Screening for active TB should be part of the
clinical evaluation of patients being considered for HBV and/or HCV and
HIV treatment. WHO recommends a four-symptom screening algorithm to rule
out active TB (
412).
In the absence of a cough, weight loss, fever and night sweats, active
TB can be confidently ruled out. In the presence of these symptoms,
further investigations for TB would be recommended.
Drug interactions. Drug-induced liver injury is three- to
sixfold higher in persons coinfected with HBV, HCV or HIV who are
receiving antituberculosis drugs. All existing DAA combination regimens
interact with rifampicin, but there are no serious interactions
anticipated between sofosbuvir or daclatasvir and multidrug-resistant
(MDR) or extensively drug-resistant (XDR)-TB regimens (
469).
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).
Implementation considerations
Knowledge of the underlying prevalence of viral hepatitis as well as
other important diseases of public health significance in migrants and
refugees is key for an effective country programme.
Barriers to testing uptake among migrant groups, such as language and
cultural barriers, need to be addressed in order to increase uptake of
testing (
193). There
is evidence that provision of information and education on hepatitis B
to migrant populations may improve knowledge about risk, screening and
prevention (
470), but
not necessarily lead to increased uptake of testing.
Persons who have travelled to high-prevalence countries and had an
invasive procedure, including tattoos, acupuncture, body piercings, with
equipment that may not have been properly sterilized, or those who may
have engaged in high-risk sexual behaviours or injecting drug use should
also be considered for targeted testing.
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).
Implementation considerations
In all settings, testing for hepatitis B (and in many settings for hepatitis C)
and the offer of HBV vaccination to health-care workers who are non-immune
should be standard practice, but this is currently not widely implemented in
LMICs.
Infection control and injection safety. In settings where
infection control practices and occupational health and safety standards
are inadequate, testing initiatives should take place alongside
improvements in safety standards and procedures to protect health-care
workers against possible exposure.
Post-exposure prophylaxis. In the event of exposure to HBV,
post-exposure prophylaxis with HBV vaccine and HBIG should be made
available for health-care workers exposed to HBV where the worker has
not received vaccination or where the antibody response to HBV
vaccination is unknown.
Early diagnosis and management of chronic hepatitis B and C
infection should be available to all health-care workers where
occupational transmission of HBV or HCV has occurred. Those who are
HBsAg positive and undertake exposure-prone procedures, such as
surgeons, gynaecologists, nurses, phlebotomists, personal care
attendants and dentists, should be considered for HBV antiviral therapy
to reduce direct transmission to others, and DAA therapy for HCV.
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.
Implementation considerations
Testing for couples who ask to be tested together promotes mutual disclosure of
status and increases adoption of prevention measures, especially in the case of
discordant couples.
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).
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.
Implementation considerations
Integration with HIV testing. WHO now recommends HIV testing
for all pregnant women (
11). The offer of HBV testing alongside existing HIV testing
and PMTCT interventions is an effective and efficient mechanism of
scaling up HBV testing for pregnant women and their partners.
Information on risk factors for HCV infection should be communicated to
pregnant women and, if present, or in high-endemic settings, testing for
HCV should also be considered alongside testing for HIV and HBV.
Timing of testing. Testing should be done as early as
possible during pregnancy to enable pregnant women to benefit most from
prevention, treatment and care, and to reduce the risk of transmission
to their infants. It can also be performed late in pregnancy, in labour
or, if that is not feasible, as soon as possible after delivery.
Pre- and post-test counselling. Pre-test information for
women who are or may become pregnant or who are postpartum should
include: the benefits of early diagnosis of HBV or HCV infection for
their own health, as well as to reduce the risk of HBV or HCV
transmission to the infant; and importance of testing also for HIV and
syphilis. Post-test counselling should include: use of antiviral therapy
for the mother's health as appropriate; measures to reduce the
risk of transmitting HBV or HCV infection to the infant; encouragement
for partner testing; advice on childbirth plans and infant-feeding
options with an encouragement to deliver in a health facility to ensure
access to PMTCT services; and HBV and HCV testing for the infant.
Linkage to care. There is a significant loss to follow up of
pregnant women testing HBV- or HCV-positive who need to be linked to
care to assess the need for antiviral treatment and ongoing monitoring.
Pregnant women without any serological markers for HBV can be offered
HBV vaccination. Follow up should continue through the breastfeeding
period to ensure that infants born to mothers with CHB receive the
recommended three doses of vaccine, especially if they did not receive
the HBV birth-dose vaccination.
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.
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).
Implementation considerations
Service delivery – delivering adolescent-friendly
services. Engaging adolescents in testing for both HIV and
viral hepatitis, either within the health services or community, should
be based on adolescent-friendly principles to ensure that psychological
as well as physical needs are addressed. Services need to be convenient
and available, offer flexible opening hours and/or walk-in or same-day
appointments. Separate hours and special events for adolescents may help
overcome concerns that they will be seen attending viral hepatitis/HIV
services by relatives or neighbours.
Disclosure. Adolescents may particularly need support with
when and to whom to disclose a positive status (
474). When appropriate,
and only with the adolescent's specific permission, health-care
personnel should engage the support of adults – family members,
teachers, community members.
Vulnerable adolescents. Special considerations are needed
for particularly vulnerable adolescents, such as those living on the
streets, orphans, boys who have sex with men, adolescents in
child-headed households, girls engaged in sex with older men, in
multiple or concurrent sexual partnerships, or those who are sexually
exploited (
25).
Specific campaigns, use of social media or other web-based approaches,
and involving adolescents in identifying appropriate language may help
to reach this group in some settings.
Age of consent. The age of consent for HIV testing varies
from country to country, and this can pose barriers to
adolescents' access to HIV and viral hepatitis testing (
474). Testing services
should be aware of laws and policies governing the age of consent, and
develop appropriate procedures based on this legal framework to ensure
that children and adolescents have access to testing. WHO also
recommends that children and adolescents themselves be involved in the
testing decision as much as possible (
474).
Further reading
HIV and
adolescents: guidance for HIV testing and counselling and care for
adolescents living with HIV.
Geneva:
WHO;
2013 [PubMed: 25032477] (474).