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The American College of Physicians (ACP) has issued best practice advice for treating patients with chronic hepatitis C virus (HCV), which has been published in the Annals of Internal Medicine.
The Best Practice Advice report was written by the ACP Scientific Medical Policy Committee1 and is based on the World Health Organization’s (WHO’s) “Guidelines for the Care and Treatment of Persons Diagnosed With Chronic Hepatitis C Virus Infection,”2 updated July 2018.
“Although the WHO guideline is primarily targeted toward policymakers in low- and middle-income countries, recommendations are relevant to the United States, where equity and resource allocation issues are also important considerations,” the ACP stated. “We discuss implications of the WHO recommendations for clinicians and patients in the United States.”
The WHO recommends offering treatment to all patients aged 12 years and older with chronic HCV infection and specifies 3 major considerations for the guideline-supported “treat-all” strategy: the effectiveness and safety of direct-acting antiviral agents (DAAs), the emergence of pangenotypic drug regimens,and the reduction in treatment costs.
Currently, combination therapy with oral DAAs has replaced interferon and ribavirin for patients with HCV. The WHO recommends pangenotypic regimens that simplify pretreatment and on-treatment testing, affording providers an opportunity to “simplify and reduce the cost of care without compromising care quality.” This is in contrast with guidance from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America, which supports the use of specific DAA regimens selected based on genotype and intensive laboratory testing before and after treatment.
The WHO defines pangenotypic treatment regimens as those that achieve a rate of sustained virologic response (SVR) greater than 85% across all major HCV genotypes. Of note, the sofosbuvir–daclatasvir regimen has “fallen out of favor” in the United States following “inferior response rates in non–head-to-head comparisons with other regimens in registration trials,” according to Abraham et al.
The WHO defines successful HCV treatment as therapy that leads to an undetectable viral load 12 weeks after treatment completion (SVR12). Pangenotypic DAA regimens are highly effective, with pooled SVR12 rates exceeding 85% to 90%. Findings from studies involving interferon-based treatment have shown that achievement of SVR12 reduces illness associated with cirrhosis and extrahepatic manifestations of HCV. “However, direct evidence that DAA treatment regimens lead to these patient-important outcomes is sparse, indicating an area for future research,” according to the ACP.
A treat-all approach is estimated to prevent 0.57 infections over 20 years for each person treated, and although some of the parameters that inform the WHO model, such as the population growth rate, are lower in the United S, “the population benefits of treating all patients with HCV are still likely to be meaningful,” Abraham et al state.
However, it is important to note that while DAA regimens are well tolerated and have mild adverse effects, broader use could lead to more severe adverse effects, according to the WHO. As a result, they urged caution about an increased risk for hepatitis B reactivation during HCV treatment.
“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,” the ACP authors stated. “Most patients support a treat-all strategy, but some express concern about adverse effects and costs.”
The WHO’s recommendations have implications for high-value care, noted the ACP Scientific Medical Policy Committee. For example, wider adoption of pangenotypic regimens in the US would underscore the need for viral genotyping prior to treatment, except with use of glecaprevir–pibrentasvir (GLE–PIB). In addition, pretreatment testing is required only to distinguish patients with cirrhosis from those without cirrhosis to determine treatment duration, which can be performed at a low cost with noninvasive tests.
Further, many patients with uncomplicated HCV infection do not require a specialist or intensive laboratory monitoring.1 However, patients with decompensated cirrhosis, hepatitis B or HIV co-infection, or chronic kidney disease “should be managed in consultation with a specialist and likely require more careful laboratory monitoring,” the ACP authors stated. This also applies to women who are pregnant and patients for whom a DAA regimen has been unsuccessful.
Affordability remains a barrier to DAA treatment, with the cost in the United States varying greatly, according to the ACP. “The opportunity to prevent the transmission of HCV must be considered when cost-effectiveness is discussed,” Abraham et al observed.
Pangenotypic regimens with a short duration of therapy (8 to 16 weeks) can now achieve virologic cure rates (SVR12) of more than 90% in chronic hepatitis C disease. Referral to a subspecialist is not necessary, owing to the simplicity of testing and treatment regimens, especially with sofosbuvir–velpatasvir.
Similarly, invasive testing to establish the degree of fibrosis is not necessary; inexpensive laboratory tests can reliably identify patients with cirrhosis, the ACP Scientific Medical Policy Committee notes. Viral genotyping, however, is necessary in instances when GLE-PIB is pursued.
Regarding the best practices for treating patients with or without cirrhosis, the ACP advises that patients aged 18 years or older without cirrhosis receive sofosbuvir–velpatasvir for 12 weeks or GLE–PIB for 8 weeks (16 weeks in cases with known genotype 3 infection). Patients with compensated cirrhosis should receive 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,” stated Abraham et al. “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.”
The ACP developed its best practice advice with the goal of simplifying and improving the treatment of patients with HCV; the paper is based on an evaluation of the benefits, harms, and cost of HCV treatment. “By following ACP’s best practice advice, physicians can practice high value care by offering treatment to all patients with chronic HCV infection using a ‘treat-all’ strategy without any invasive testing,” stated Jacqueline W. Fincher, MD, president of the ACP, in a statement.2
References
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. ACP issues best practice advice on treatment of hepatitis C virus infection. News release. The American College of Physicians. October 6, 2020. Accessed November 2, 2020.
