A Closer Look at the Updated WHO HCV Guidelines

Driven by the rapid development of highly effective, direct acting antiviral (DAA) drugs, the treatment of chronic hepatitis C virus (HCV) infection has undergone a transformation over the last 5 years. In an effort to keep pace with these changes, the World Health Organization (WHO) recently published an update to its Guidelines for the screening, care and treatment of persons with hepatitis C infection, two years after their initial release in 2014.¹ Even in that short period, several new medications have been added to the arsenal of DAAs and are now featured prominently in the updated guidelines and on the WHO Model List of Essential Medicines. These medications include: ledipasvir, daclatasvir, and the combination of ombitasvir, paritaprevir, and dasabuvir. Although the primary audience for these guidelines is physicians and policymakers in low- and middle-income countries, to assist in developing country-specific treatment guidelines and programs, the new guidelines closely mirror treatment recommendations followed in high-income countries, including the United States, and are now applicable for all countries.

The most significant update in the new guidelines is the strong recommendation that DAA regimens be considered the preferred first-line treatment options, replacing older regimens that continued to include pegylated interferon/ribavirin. In addition, the use of the first-generation DAAs, telaprevir or boceprevir, is no longer recommended. These changes are supported by the favorable efficacy, administration, and safety profile of the new DAA-based regimens, which are all-oral, have a low pill burden (as few as 1 pill/day), require short treatment durations (typically 12 weeks), are well-tolerated, and boast cure rates that exceed 90%. It should be noted that the guidelines acknowledge that some HCV-infected patients may still require pegylated interferon and/or ribavirin to optimize the chance of being cured, based on their HCV genotype or extent of liver disease. However, with the promise of highly effective, pan-genotypic DAA regimens on the horizon, this caveat may soon be of a bygone era as well.

These new recommendations bring the WHO guidelines more in line with the US HCV treatment guidelines issued by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), which have recommended against the use of these first-generation protease inhibitors since early 2014 and adopted all-oral DAA regimens as first-line treatment options starting in November 2014.²

Further updates to the WHO guidelines include important discussion on the impact that prioritizing DAA-based regimens will have on treatment availability in resource-limited settings. It is anticipated that scale-up of all-oral DAA regimens will be economically feasible and widely accessible. The favorable administration and safety profile of the new DAA-only regimens, such that weekly injections and/or frequent lab monitoring are not required, would allow for HCV treatment services to be expanded beyond traditional medical clinics to target difficult-to-reach populations such as people who inject drugs (PWID). In addition, successful price negotiations with drug manufacturers to lower drug prices and the introduction of generic medicines suggest that DAA-only regimens can be more cost-effective than older regimens.

In sharp contrast to the AASLD/IDSA guidelines extensively referenced in the United States that advocate for the treatment of all persons with HCV infection, the WHO guidelines fall short of making a firm recommendation on treatment allocation or prioritization. Despite optimism for the scalability of DAA-based regimens, WHO acknowledges that ongoing high costs and limited healthcare infrastructure in many countries may prevent full treatment scale-up. With this in mind, the guidelines issue a framework intended to guide policymakers as they set out to develop in-country HCV treatment programs. Emphasizing both clinical and public health goals, the guidelines call for prioritizing treatment for: (1) those with advanced HCV-related liver disease and (2) those with the highest risk of transmitting HCV infection.

The updated 2016 WHO guidelines highlight the tremendous strides that have been made in the ongoing march toward a world free of hepatitis C, yet, there remains much work to be done. Recent studies are more convincingly demonstrating the detrimental consequences of untreated HCV infection while also highlighting huge gaps in awareness of their diagnosis or accessibility of treatment among infected persons. Today, WHO estimates that approximately 700,000 persons worldwide die each year from HCV-related complications.¹ However, at a time when we boast of medicines that can cure over 9 in 10 people with HCV, each HCV death should be considered a public health failure. Thus, it remains incumbent among us as healthcare professionals to build on these guidelines to advocate for the most effective and safest treatment options for our individual patients and all patients worldwide.

References

1. World Health Organization. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection. WHO website. www.who.int/hepatitis/publications/hepatitis-c-guidelines-2016/en/. Updated April 2016. Accessed April 27, 2016.
2. AASLD/IDSA. HCV Guidance: Recommendations for testing, managing and treating hepatitis C. HCV Guidelines website. http://www.hcvguidelines.org/. Accessed April 27, 2016.