Based on updated evidence-based guidelines issued by the World Health Organization (WHO) in 2018, the American College of Physicians (ACP) recently issued best practice advice that simplifies and improves the treatment of chronic hepatitis C virus (HCV).The guidance has been published in Annals of Internal Medicine.1 According to the ACP, although the WHO guidelines are targeted toward low-and middle-income countries, the recommendations are still relevant to the United States.2

The WHO guidelines recommended the treatment of all patients with chronic HCV aged 12 years and older, and noted 3 major considerations for selection of therapy: effectiveness and safety of direct-acting antiviral agents (DAAs), emergence of pangenotypic drug regimens, and reductions in the cost of treatment. The ACP indicated that while the parameters and population used in the “treat-all” model by the WHO may differ from the United States, the population benefits of treating all patients with HCV are likely to be meaningful. The WHO estimated that this approach could prevent 0.57 infections per person over the course of 20 years.

The WHO recommended pangenotypic regimens that simplify pre- and on-treatment testing, which differ from guidance from both the American Association for the Study of Liver Disease and the Infectious Diseases Society of America, who recommend DAA treatment based on genotype and intensive laboratory monitoring before and during therapy. The WHO notes that while DAA regimens are well tolerated, their broader use could uncover more serious adverse events. Use of DAAs heighten the risk for hepatitis B reactivation, and potentially divert attention and resources from HCV harm-reduction interventions. Patients with decompensated cirrhosis, hepatitis B or HIV co-infection, chronic kidney disease, and history of unsuccessful DAA regimens are likely to require more careful monitoring.

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ACP Best Practice Advice

  • Viral genotyping is unnecessary when treating chronic HCV with pangenotypic medications. An exception would be with glecaprevir-pibrentavir (GLE-PIB), where identification of genotype 3 is necessary before initiation.
  • Invasive testing to determine the degree of fibrosis is unnecessary, as inexpensive tests can reliably identify cirrhosis, which determines treatment duration.
  • The WHO suggested the use of noninvasive techniques in clinical circumstances where a more refined assessment of the degree of precirrhotic fibrosis is needed.

Treatment Recommendations

Patients Aged 18 Years and Older Without Cirrhosis

  • Sofosbuvir-velpatasvir for 12 weeks
  • GLE-PIB for 8 weeks
  • GLE-PIB extended to 16 weeks for genotype 3 infection

Patients Aged 18 Years and Older With Compensated Cirrhosis

  • Sofosbuvir-velpatasvir for 12 weeks
  • GLE-PIB for 12 weeks
  • GLE-PIB extended to 16 weeks for genotype 3 infection.

Across the United States, the average cost of DAA treatment is less than $15,000 per patient. The ACP suggests that the WHO recommendations will offer clinicians the opportunity to simplify and reduce cost of care without compromising on quality, and enable the treatment of patients with uncomplicated HCV in primary care settings.


  1. Abraham GM, Obley AJ, Humphrey LL, Qaseem A. World Health Organization guidelines on treatment of hepatitis c virus infection: best practice advice from the American College of Physicians. Ann Intern Med. Published online October 6, 2020. doi: 10.7326/M19-3860.

  2. Guidelines for the Care and Treatment of Persons Diagnosed With Chronic Hepatitis C Virus Infection. World Health Organization. Accessed November 14, 2020.