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Updated Hepatitis C Screening Recommendations Expand to Cover Adolescents, DAAs


Hepatitis C virus (HCV) has contributed to more US patient deaths than the next 60 reportable infectious diseases combined. The United States Preventive Services Task Force has issued updated guidelines on screening for HCV that account for the larger proportion of this patient group that now includes persons who inject drugs, as well as the shift from interferon-based therapy to regimens composed of direct-acting antiviral (DAA) medications.

Hepatitis C virus (HCV) has contributed to more US patient deaths than the next 60 reportable infectious disease combined.1 It is the most common chronic blood-borne pathogen in the United States, with approximately 4.1 million current and past cases.2

The United States Preventive Services Task Force (USPSTF) has updated its screening guidelines for HCV to now account for 2 major shifts in the HCV landscape2:

  1. A larger proportion of this patient group now includes persons who inject drugs (PWID), including younger adults. Data show that close to one-third of persons aged 18 to 30 years who inject drugs and 70% to 90% of older Americans who inject drugs have HCV.
  2. Oral direct-acting antiviral (DAA) medications have been introduced, and they are shown to have superior efficacy to the previous injectable interferon-based therapy.

These updated screening recommendations were published today in JAMA.

The USPSTF now “recommends screening for HCV infection in adults aged 18 to 79 years (B recommendation),” risk factors notwithstanding. The B recommendation means that “insurance companies will provide reimbursement for hepatitis C testing without cost sharing by patients,”1 as well as there being “a high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.” In addition, per the Affordable Care Act, a grade B recommendation has to be covered by private insurers and Medicaid, without a deductible or co-pay.3

The previous HCV screening guideline from 2013 carried the same B recommendation but restricted the age cohort to the baby boomer generation—those born between 1945 and 1965—because 75% of HCV infections were concentrated in that age group at that time. In addition, the CDC only called for a 1-time screening.1 A major goal of the update is to expand the asymptomatic population who is screened and to ensure sustained virologic response (SVR),4 or having an undetectable HCV level at least 12 weeks after finishing treatment,1 which can head off serious long-term complications of chronic HCV that include cirrhosis, liver failure, liver cancer, and death.5

The changes in the updated guidelines are the results of analyses of randomized clinical trials and nonrandomized treatment studies from Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews that were evaluated for mortality, morbidity, quality of life, screening and treatment harms, and screening diagnostic yield outcomes.4

The study results published in JAMA show that, compared with the previous interferon-based therapy, the newer DAA regimens decreased the risk of cardiovascular events. For example, in adults, the incidence rate per 1000 person-years of follow-up was 16.3 (95% CI, 14.7-18.0) for DAA therapy, 23.5 (95% CI, 21.8-25.3) for interferon-based therapy, and 30.4 (95% CI, 29.2-31.7) for no therapy (P <.001 for antiviral therapy vs no therapy). Additional results for adolescents between 12 and 15 years old, 35% to 66% of whom were female, from 7 studies show that “across all intervention studies of DAA in adolescents, the SVR rate ranged from 97% to 100%.”4

SVR was also associated with “significantly decreased all-cause mortality.” Studies with a follow-up beyond 5 years had a pooled hazard ratio of 0.33 (95% CI, 0.24-0.46) compared with 0.64 (95% CI, 0.56-0.74) (P = .003 for interaction) among studies that had shorter follow-ups.4

It’s when the SVR rates were pooled, however, that the true effectiveness of DAA therapy can be seen. In the United States, HCV genotype 1 is the most common HCV infection, and DAA therapy was shown to contribute to a pooled SVR rate of 97.7% (95% CI, 96.6%-98.4%; I2 = 82%). In other genotypes, the pooled SVR rates were just as high4:

  • Genotype 2: 98.9% (95% CI, 97.5%-99.5%; I2 = 4%)
  • Genotype 3: 95.5% (95% CI, 91.6%-97.7%; I2 = 66%)
  • Genotype 4: 98.2% (95% CI, 94.7%-99.4%; I2 = 50%)

Overall, because there is a need for more direct evidence of the effects of DAAs on clinical outcomes, the JAMA study authors are calling for additional clinical studies that measure quality of life and the association between SVR and clinical outcomes, as well as confirming the effectiveness of DAAs in adolescents.4

Those who worry the current guidelines are not expansive enough suggest that outreach and education are important to ensure those who should be screened for HCV are screened. For instance, jailed individuals account for “the largest population of HCV-infected persons; however, the proportion cured is much lower (4%), so efforts for treatment must include this group.”6 And patients, particularly those at increased risk (eg, PWID), need to know how HCV is acquired; what test results mean; how treatment will benefit them, in addition to its adverse effects; and that they can ask questions.2


1. Graham CS, Trooskin S. Universal screening for hepatitis C virus infection: a step toward elimination [published online March 2, 2020]. JAMA. doi: 10.1001/jama.2019.22313.

2. US Preventive Services Task Force. Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement [published online March 2, 2020]. JAMA. doi: 10.1001/jama.2020.1123.

3. Rosenberg ES, Barocas JA. USPSTF’s hepatitis C screening recommendation—a necessary step to tackling an evolving epidemic. JAMA Netw Open. 2020;3(3):e200538. doi: 10.1001/jamanetworkopen.2020.0538.

4. Chou R, Dana T, Fu R, et al. Screening for hepatitis C virus infection in adolescents and adults: updated evidence report and systematic review for the US Preventive Services Task Force [published online March 2, 2020]. JAMA. doi: 10.1001/jama.2019.20788.

5. Jin J. Screening for hepatitis C virus infection [published online March 2, 2020]. JAMA. doi: 10.1001/jama.2020.1761.

6. Price JC, Brandman D. Updated hepatitis C virus screening recommendation—a step forward [published online March 2, 2020]. JAMA Intern Med. doi: 10.1001/jamainternmed.2019.7334.

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