Updated recommendations on treatment of adolescents and children with chronic HCV infection, and HCV simplified service delivery and diagnostics

EXECUTIVE SUMMARY

Hepatitis C virus (HCV) infection is a major public health problem and cause of chronic liver disease that leads to approximately 399 000 deaths annually. In 2019, WHO estimated that 58 million persons were chronically infected and living with hepatitis C, with a disproportionately high burden in low- and middle-income countries (LMICs). In 2016, WHO developed the global health sector strategy on viral hepatitis 2016–2021, with the ambitious goal to eliminate viral hepatitis as a public health threat by 2030. While good progress has been made in several champion countries, there remains a major testing and treatment gap. In 2019, only 21% of the 58 million persons with chronic HCV infection had been diagnosed, and 13%, treated. Achieving HCV elimination will require a radical simplification in care pathways to overcome barriers in access to HCV testing and treatment.

The objective of these guidelines is to provide updated evidence-based recommendations on the priority HCV-related topics from the 2018 WHO Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C infection and the 2017 WHO Guidelines on hepatitis B and C testing. These priority areas are:

• direct-acting antiviral (DAA) treatment of adolescents and children ages ≥3 years of age

• simplified HCV service delivery (decentralization, integration and task sharing)

• HCV diagnostics – use of point-of-care (POC) HCV ribonucleic acid (RNA) assays and reflex HCV RNA testing.

These guidelines also update existing chapters without new recommendations, such as the inclusion of new manufacturers’ protocols on the use of dried blood spot (DBS) for HCV RNA testing and new data to inform the limit of detection for HCV RNA assays as a test of cure, in addition to their use for diagnosis.

Overall, this guideline update is consistent with the modular approach to updating guidelines for diagnosis and treatment of chronic hepatitis B and C virus infections B adopted since 2020 (that is, periodic updating of specific sections or chapters in response to emerging evidence). In July 2021, the first modular update on hepatitis C self-testing guidelines was launched. This guidelines update represents the second modular update on hepatitis C testing and treatment. In 2023, all updates will be compiled along with existing recommendations into a single consolidated guidelines on prevention, testing, care and treatment of hepatitis B and C, containing all relevant guidance.

Five systematic reviews and meta-analyses were undertaken to address the key research questions, in addition to four values and preferences surveys to assess perspectives of affected communities and health workers, cost–effectiveness analyses and a series of case studies on implementation experience to inform the process of formulating recommendations.

The main areas of new recommendations are:

• Treatment in adolescents and children: Expansion of the 2018 “treat all” recommendation for all adults to now include all adolescents and children with chronic HCV infection ages three years or older, with use of the same pangenotypic DAA regimens already recommended in adults (sofosbuvir/daclatasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir).

• Simplified service delivery: Expansion of HCV testing and treatment services, ideally at the same site, through decentralization of care to lower-level facilities; integration with existing services, such as in primary care, harm reduction, prisons and HIV services; and promotion of task sharing through delivery of HCV testing, care and treatment by trained but non-specialist doctors and nurses.

• HCV RNA testing: The use of PoC HCV RNA assays is now recommended as an additional approach to diagnose viraemic infection, especially among marginalized populations, such as persons who inject drugs, and hard-to-reach communities with constrained access to health care and that have high rates of loss to follow-up. Reflex HCV RNA testing in those with a positive HCV antibody is recommended as an additional strategy to promote linkage to care and treatment. This can be achieved either through laboratory-based reflex HCV RNA testing using a specimen already held in lab or clinic-based reflex testing in a health facility through immediate specimen collection for HCV RNA testing following a positive rapid HCV antibody test result, avoiding the need for a second visit and further blood sample.

These guidelines are addressed primarily to national hepatitis programme managers and other policy-makers in ministries of health, particularly in LMICs, who are responsible for the development of national hepatitis testing and treatment plans, policy and guidelines. Implementation of the recommendations in these guidelines should be informed by local context, including HCV epidemiology and prevalence of other comorbidities, availability of resources, the organization and capacity of the health system and anticipated cost–effectiveness.