World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians

“The World Health Organization (WHO) updated its evidence-based guideline on chronic HCV infection in July 2018. [..] We discuss implications of the WHO recommendations for clinicians and patients in the United States.

The WHO recommends offering treatment to all persons older than 12 years who have chronic HCV infection, and it notes 3 major considerations for this “treat all” strategy: the effectiveness and safety of direct-acting antiviral agents (DAAs), the emergence of pangenotypic drug regimens, and reduction in the cost of treatment. In current treatment regimens, combination therapy with oral DAAs has replaced interferon and ribavirin. The WHO recommends pangenotypic regimens that simplify pretreatment and on-treatment testing. [..] The WHO recommendations offer U.S. clinicians the opportunity to simplify and reduce the cost of care without compromising care quality.

[..] The WHO estimates that a treat all approach would prevent 0.57 infections over 20 years for each person treated. Although some of the parameters used in the WHO model, such as population growth rate and HCV prevalence, are lower in the United States, the population benefits of treating all patients with HCV are still likely to be meaningful. The WHO notes that DAA regimens are well tolerated and have mild adverse effects but acknowledges that broader use of DAAs could uncover more severe adverse effects. It also cautions about the heightened risk for hepatitis B reactivation during HCV treatment, as well as the possibility that a treat all approach could divert attention and resources from interventions for HCV harm reduction. Drug interactions with DAAs are also important to consider, especially because commonly used drugs, such as proton-pump inhibitors, statins, antidepressants, and antiretroviral therapy, can inactivate some DAAs. Most patients support a treat all strategy, but some express concern about adverse effects and costs.

[..] First, wider adoption of pangenotypic regimens in the United States would obviate the need for viral genotyping before treatment is started (except when using glecaprevir–pibrentasvir [GLE–PIB], in which case genotyping is necessary to identify genotype 3, which requires longer treatment). Second, pretreatment testing is required only to distinguish patients with cirrhosis from those without to determine treatment duration, a distinction reliably made with inexpensive, noninvasive tests. When clinical circumstances require a more refined assessment of the degree of precirrhotic fibrosis, noninvasive techniques, such as vibration-controlled transient elastography, can be considered in lieu of liver biopsy. Third, many patients with uncomplicated HCV infection do not require specialist involvement, and laboratory monitoring can be limited to the beginning and end of treatment. Patients with decompensated cirrhosis, hepatitis B or HIV co-infection, or chronic kidney disease; pregnant women; and those in whom a prior DAA regimen has been unsuccessful should be managed in consultation with a specialist and likely require more careful laboratory monitoring.

[..] the WHO has developed a calculator ( that estimates the cost-effectiveness of HCV treatment in 28 countries that it has deemed high-priority by applying its customary willingness-to-pay threshold of 3 times the per capita gross domestic product of the country. The cost of a 4-week DAA regimen in the online model ranges from $15 in Pakistan to $73,944 in Romania. Although the United States is not represented in the WHO cost-effectiveness calculator and the cost of DAA treatment in the United States can vary greatly on the basis of several factors, the average cost of treatment has decreased and may now be less than $15,000 per patient. In comparison, the total lifelong cost of HIV treatment with darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is $1.2 million.

[..] Treatment of chronic hepatitis C disease has reached a stage where pangenotypic regimens with shorter durations of therapy (8 to 16 weeks) can achieve virologic cure rates (SVR12) of more than 90%. Improving affordability and availability worldwide are important next steps in universal reduction in the prevalence of this disease. Given the simplicity of the testing and treatment regimens, particularly with sofosbuvir–velpatasvir, referral to a subspecialist is not necessary.

[Best Practice Advice] Viral genotyping is unnecessary when treating HCV with pangenotypic medications unless planning treatment with GLE–PIB. Invasive testing to establish the degree of fibrosis is not necessary, and inexpensive laboratory tests can reliably identify patients with cirrhosis. Patients aged 18 years or older without cirrhosis should receive sofosbuvir–velpatasvir for 12 weeks or GLE–PIB for 8 weeks (16 weeks in cases with known genotype 3 infection). Those with compensated cirrhosis should be treated with sofosbuvir–velpatasvir for 12 weeks or GLE–PIB for 12 weeks (16 weeks in cases with known genotype 3 infection). Laboratory monitoring can be limited to the beginning and end of the treatment in adults with no or compensated cirrhosis. Patients with decompensated cirrhosis will need closer monitoring. The simplification of treatment and monitoring enables patients with uncomplicated HCV infection to receive treatment in primary care settings.”

Full article, Abraham GM, Obley AJ, Humphrey LL et al. Annals of Internal Medicine 2020.10.6