1.1. Objectives
The objective of these guidelines is to provide updated evidence-based recommendations on the care and treatment of persons with chronic hepatitis C virus (HCV) infection in terms of when to treat and what treatment to use in children, adolescents and adults.
1.2. New developments and rationale for an update of the guidelines
In 2014, WHO published its first Guidelines for the screening, care and treatment of persons with HCV infection (1). The care and treatment component of the 2014 Guidelines were updated a first time in 2016 (2) and a second time with the present guidelines. In parallel, the 2017 Guidelines on testing for viral hepatitis recommended which approaches to use in terms of who to test and how to test (3).
The 2016 Guidelines for the screening, care and treatment of persons with HCV infection recommended DAA regimens for the treatment of persons with HCV infection (2). While all HCV-infected persons could be considered for treatment, the Guidelines also highlighted key factors to consider in prioritizing treatment (i) for those likely to derive the greatest individual benefit, or (ii) in populations deriving the greatest treatment benefit from limiting HCV transmission. Those with the highest risk of mortality and morbidity include those at risk of accelerated fibrosis, metabolic syndrome and extrahepatic manifestations. Those for whom treatment could lead to a reduction in incidence included PWID, HIV-infected MSM, prisoners, sex workers and health-care workers.
Since the 2016 Guidelines for the screening, care and treatment of persons with HCV infection, three key developments prompted changes in terms of when to treat and what treatment to use:
The generalized use of safe and highly effective direct-acting antiviral (DAA) medicine regimens for all persons improves the balance of benefits to harms of treating persons with little or no fibrosis, supporting a strategy of treating all persons with chronic
HCV infection, rather than reserving treatment for persons with more advanced disease. Prior to 2014, HCV treatment involved the use of interferon-based regimens with generally low rates of cure, long duration of therapy and substantial toxicities. The introduction of highly effective and well tolerated short-course oral DAA therapy that can cure HCV infection with high rates of sustained virological response (SVR) within weeks transformed the treatment landscape for persons with chronic HCV infection. Since the 2016
Guidelines, DAA regimens have continued to improve.
Several new, pangenotypic DAA medicines have been approved by at least one stringent regulatory authority, reducing the need for genotyping to guide treatment decisions.
Pangenotypic DAA combination regimens approved by the United States Food and Drug Administration (
FDA) and European Medicines Agency (
EMA) include sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. These regimens achieve high treatment efficacy across all six major
HCV genotypes, including in those with cirrhosis or
HIV coinfection. In addition, the Guidelines Development Group considered sofosbuvir/daclatasvir, commonly used in
LMICs, as a pangenotypic regimen, based on all the available evidence from clinical trials and observational studies in different settings.
The continued substantial reduction in the price of DAA regimens has enabled treatment to be rolled out rapidly in a number of low- and middle-income countries (
LMICs)
(4).
Together, these three factors have shifted the balance of benefits and risks in favour of treating all persons with chronic HCV infection with pangenotypic regimens.
1.3. Target audience
Although the recommendations included in these guidelines apply to all countries, the key audience for these guidelines is policy-makers in ministries of health in LMICs. The recommendations are intended for government officials to use as the basis for developing national hepatitis policies, plans and treatment guidelines. For countries with existing national plans/programmes, these guidelines can guide updates of national hepatitis treatment guidelines and for deciding which medicines to use. In addition, implementing partners can use the guidelines to inform the design and implementation of treatment services. The guidelines are also intended to be helpful for clinicians who treat HCV-infected persons.
1.4. Scope of the guidelines
The recommendations in these guidelines address treatment issues. However recommendations related to prevention, testing and care are referred to in order to reinforce the importance of the continuum of care (including identification of infected persons) that is a key element of the clinical management of HCV infection. The management of acute HCV infection was not included in the scope of work for these guidelines.
1.5. Related guidelines
These guidelines are intended to complement existing guidance on the primary prevention of HCV and other bloodborne viruses by improving blood and injection safety, and health care for people who inject drugs (PWID) and other vulnerable groups, including those living with HIV.
Additional guidance relevant to the prevention, care and treatment of those infected with HCV can be found in the following documents:
Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations. Geneva:
WHO; 2016 update
(5) Guidelines for the prevention, care and treatment of persons with hepatitis B infection. Geneva:
WHO; 2015
(6) WHO guideline on the use of safety-engineered syringes for intramuscular, intradermal and subcutaneous injections in health-care settings. Geneva: WHO; 2016
(7) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva:
WHO; 2016
(8) Guidelines on hepatitis B and C testing. Geneva:
WHO; 2017
(3)
1.6. Guiding principles
The following principles have informed the development of these guidelines and should guide the implementation of the recommendations.
The guidelines will contribute to realizing the Sustainable Development Goals through achieving key global and national hepatitis goals.
The guidelines are based on a public health approach to scaling up the use of antiviral treatment for
HCV infection along the continuum of hepatitis prevention, care and treatment.
Implementation of the guidelines need to be accompanied by efforts to promote and protect the human rights of people who need hepatitis services, including ensuring informed consent, preventing stigma and discrimination in the provision of services and promoting gender equity.
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.n
