Adults aged 18-79 years should be screened for hepatitis C virus infection, according to an updated grade B recommendation from the U.S. Preventive Services Task Force.
Cases of acute hepatitis C virus (HCV) infection have spiked in the last decade, in part because of increased use of injection drugs and in part because of better surveillance, Douglas K. Owens, MD, of Stanford (Calif.) University, and colleagues wrote in the recommendation statement published in JAMA.
The recommendation applies to all asymptomatic adults aged 18-79 years without known liver disease, and expands on the 2013 recommendation to screen adults born between 1945 and 1965. The grade B designation means that the task force concluded with moderate certainty that HCV screening for adults aged 18-79 years had “substantial net benefit.”
The recommendations are based on an evidence report including 8 randomized, controlled trials, 48 other treatment studies, and 33 cohort studies published through February 2019 for a total of 179,230 individuals.
The screening is a one-time procedure for most adults, according to the task force, but clinicians should periodically screen individuals at increased risk, such as those with a past or current history of injection drug use. In addition, clinicians should consider screening individuals at increased risk who are above or below the recommended age range.
Although the task force identified no direct evidence on the benefit of screening for HCV infection in asymptomatic adults, a notable finding was that the newer direct-acting antiviral (DAA) regimens are sufficiently effective to support the expanded screening recommendation, they said. However, clinicians should inform patients that screening is voluntary and conducted only with the patient’s knowledge. Clinicians should educate patients about hepatitis C and give them an opportunity to ask questions and to make a decision about screening, according to the task force.
In the evidence report, a total of 49 studies including 10,181 individuals showed DAA treatment associated with pooled sustained virologic response rates greater than 95% across all virus genotypes, and a short-term serious adverse event rate of 1.9%. In addition, sustained virologic response following an antiviral therapy was associated with a reduction in risk of all-cause mortality (pooled hazard ratio 0.40) and of hepatocellular carcinoma (pooled HR 0.29) compared with cases of no sustained virologic response.
The evidence report findings were limited by several factors, including the relatively small number of randomized trials involving current DAA treatments, limited data on baseline symptoms, limited data on adolescents, and limited evidence on potential long-term harms of DAA therapy, noted Richard Chou, MD, of Oregon Health & Science University, Portland, and colleagues. However, new pooled evidence “indicates that SVR rates with currently recommended all-oral DAA regimens are substantially higher (more than 95%) than with interferon-based therapies evaluated in the prior review (68%-78%),” they said.
Several editorials were published concurrently with the recommendation.
In an editorial published in JAMA, Camilla S. Graham, MD, of Harvard Medical School, Boston, and Stacey Trooskin, MD, of the University of Pennsylvania, Philadelphia, wrote that the new recommendation reflects changes in hepatitis C virus management.
“With the approvals of sofosbuvir and simeprevir in 2013, patients with hepatitis C, a chronic viral illness associated with the deaths of more U.S. patients than the next 60 reportable infectious diseases combined, including HIV and tuberculosis, could expect a greater than 90% rate of achieving sustained virologic response (SVR, defined as undetectable HCV levels 12 weeks or longer after treatment completion, which is consistent with virologic cure of HCV infection) following 12 weeks of treatment,” they said.
These medications are effective but expensive; however, the combination of the availability of generic medications and the ongoing opioid epidemic in the United States are important contributors to the expanded recommendations, which “are welcome,” and may help meeting WHO 2030 targets for reducing new HCV infections, they said.
Dr. Graham disclosed personal fees from UpToDate. Dr. Trooskin disclosed grants from Gilead Sciences and personal fees from Merck, AbbVie, and Gilead Sciences.
In an editorial published in JAMA Internal Medicine, Jennifer C. Price, MD, and Danielle Brandman, MD, both of the University of California, San Francisco, wrote that “the advancements in HCV diagnosis and treatment have been extraordinary,” but that the new recommendation does not go far enough. “Implementation of HCV screening and linkage to treatment requires large-scale coordinated efforts, innovation, and resources. For example, point-of-care HCV RNA testing would enable scale-up of HCV screening and confirmatory testing among individuals at greatest risk of HCV infection,” they said. “Additionally, barriers remain between diagnosis and treatment, such as access to a health care provider who can treat HCV and authorization to receive affordable DAAs,” they noted. “Although the USPSTF HCV screening recommendation is a step forward for controlling HCV infection in the U.S., it will take a coordinated and funded effort to ensure that the anticipated benefits are realized,” they concluded.
Dr. Price disclosed research funding from Gilead Sciences and Merck. Dr. Brandman disclosed research funding from Gilead Sciences, Pfizer, Conatus, Allergan, and Grifols, as well as personal fees from Alnylam.
In an editorial published in JAMA Network Open, Eli S. Rosenberg, PhD, of the University at Albany (N.Y.) School of Public Health, and Joshua A. Barocas, MD, of Boston University, emphasized the need to change the stigma surrounding HCV infection in the United States.
“Given the changing epidemiology of HCV infection, new public health priorities, advancements in treatment, and unmet diagnostic needs, it is wise to periodically reevaluate screening recommendations to ensure that they are maximally addressing these areas and patients’ individual needs,” they said. “The Affordable Care Act requires private insurers and Medicaid to cover preventive services recommended by the USPSTF with a grade of A or B with no cost sharing (i.e., no deductible or copayment),” they noted. Although the new recommendation for one-time screening will likely identify more cases, improve outcomes, and reduce deaths, the editorialists cautioned that “one-time screening should not be interpreted like catch-up vaccinations, whereby we immunize someone at any age for hepatitis B virus, for example, and they are then immunized for the remainder of their life,” and that reassessments are needed, especially for younger adults.
In addition, they emphasized the need to reduce the stigma surrounding HCV and allow for recommendations based on risk, rather than age. “We have forced the USPSTF to adopt age-based screening recommendations because we, as a society, have created a culture in which we have stigmatized these behaviors and we, as practitioners, have proven to be inadequate at eliciting HCV risk behaviors,” they said. “Our responsibility as a society and practice community is to address structural and individual factors that limit our ability to most precisely address the needs of our patients and truly move toward HCV elimination,” they concluded.
The USPSTF is supported by the Agency for Healthcare Research and Quality. The task force researchers had no financial conflicts to disclose.
SOURCES: Owens DK et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2020.1123; Chou R et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.20788; Graham CS, Trooskin S. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.22313; Price JC and Brandman D. JAMA Intern Med. 2020 Mar 2. doi: 10.1001/jamainternmed.2019.7334; Rosenberg ES, Barocas JA. JAMA Network Open. 2020 Mar 2. doi: 10.1001/jamanetworkopen.2020.0538.