Hepatitis C Screening Needed for Adults and Adolescents

Roger Chou, MD

Much evidence on the effects of hepatitis C virus (HCV) screening on clinical outcomes is still unavailable, according to an updated evidence report and systematic review.

Roger Chou, MD, and a team of investigators conducted a review of >80 studies with >179,000 participants to update the 2013 review on HCV screening to inform the US Preventive Services Task Force (USPSTF). The team found that direct-acting antiviral regimens were associated with sustained virologic response rates >95% and few short-term harms relative to older antiviral agents.

Chou, a professor of medicine at Oregon Health & Science University, and colleagues also learned that sustained virologic response after antiviral therapy was associated with improved clinical outcomes compared to no sustained virologic response.

Based on the findings of Chou and his team, USPSTF recommended screening in adults aged 18-79 years old, regardless of known risk factors.

The investigators searched 3 databases from 2013-February 2019. Two investigators reviewed titles, abstracts, and full-text articles using eligibility criteria. The patient population among the studies for screening was asymptomatic adults and adolescents without prior HCV infection.

In an effort to evaluate patients more likely to be asymptomatic and identified by screening, the investigators only included studies in which <20% of patients had cirrhosis at baseline. The team also included randomized clinical trials of screening and currently recommended direct-acting antiviral regimens versus placebo or an outdated antiviral regimen.

Study outcomes included mortality; morbidity; quality of life; HCV transmission; sustained virologic response; harms; and screening yield. The team excluded studies that were focused on those co-infected with HIV or hepatitis B virus, patients who received transplants, and those with advanced kidney disease.

Several key questions guided the team’s review, including:

• What is the effectiveness of different risk- or prevalence-based methods for screening for HCV infection on clinical outcomes?
• What are the harms of screening for HCV infection?
• What is the effectiveness of currently recommended antiviral treatments in improving health outcomes in patents with HCV infection?
• What are the harms of currently recommended antiviral treatments?

Benefits of Screening

The key questions were established for the investigators to get answers to the benefits and harms of screening, benefits and harms of treatment, and sustained virologic response and health outcomes.None of the studies met inclusion criteria answered whether screening for HCV in pregnant and nonpregnant patients without known abnormal liver enzyme levels would reduce related mortality and morbidity or affect quality of life. What’s more, no study met inclusion criteria to discover the effectiveness of different risk- or prevalence-based methods for screening for HCV infection on clinical outcomes.

Harms of Screening

Treatment Benefits

One retrospective study of nearly 6000 patients compared risk-based HCV screening versus birth cohort screening. The findings showed that applying risk-based guidelines perfectly would screen 24.7% of the US general population and identify 76% of cases.Among the studies, none compared harms of HCV screening versus no screening. However, low-quality evidence from the task force’s recent review suggested possible negative psychological and social effects of screening. The review did not meet inclusion criteria for the investigators to include.Chou and the team included 10 quality-of-life studies of adults in their review. Two pooled analyses found that at 12 weeks after treatment, there were improvements in some measures of quality of life compared with before treatment. The differences were small—.004-.005 points on the 6-Dimensional Health State Form health utility scale and <3 points on the 36-Item Short Form Health Survey physical and mental component summary scales&mdash;and not all statistically significant.

More than 30 treatment studies reported mortality at 12-36 weeks after direct-acting antiviral therapy in adults, though there were not designed to assess such an outcome. More than 20 studies reported no deaths, while 10 reported 17 deaths (.4% overall)—10 due to recent injection drug use or use of opioid substitution therapy.

One study found direct-acting antiviral therapy versus interferon-based therapy or antiviral therapy in adults was associated with a decreased risk of cardiovascular events (IR per 1000 person-years of follow-up, 16.3; 95% CI, 14.7-18) for direct-acting antiviral therapy, (IR, 23.5; 95% CI, 21.8-25.3) for interferon-based therapy, and (IR, 30.4; 95% CI, 29.2-31.7) for no therapy; (P <.001) for antiviral versus no therapy.

Harms of Treatment

Some treatment studies of adolescents reported changes of 2-13 points on Pediatric Quality of Life Inventory (scale, 0-100) scores after treatment with direct-acting antiviral therapy compared with baseline. None of the studies evaluated mortality or long-term clinical outcomes.Many studies reported information on adults with direct-acting antiviral regimens who experienced adverse events at short-term follow-up. Such regimens were associated with slightly increased risk of any adverse event among 4 trials (RR, 1.12; 95% CI, 1.02-1.24; absolute risk difference [ARD], 8%; 95% CI, 8-15). Direct-acting antiviral therapy was also associated with increased risk of nausea in 3 trials (RR, 1.42; 95% CI, 1-2.03; ARD, 4%; 95% CI, −3 to 10).

What’s Next

Several treatment studies of direct-acting antiviral regimens in adolescents showed harms, but methods for assessing harms were not well-described, the investigators said. Adverse event rates were 27% in 1 study and ranged from 71-87% in 4 studies.The team reported that additional research could help better understand the link between use of current direct-acting antiviral therapy and clinical outcomes.

Per the new recommendation by the USPSTF that HCV infection screening should be done in adults aged 18-79 years old regardless of known risk factors, screening could be cost-effective and insurance companies would provide reimbursement for testing without cost-sharing, Camilla Graham, MD, MPH, wrote in an accompanied commentary. Adolescents who inject drugs or other behaviors without the acquisition of the infections should also be screened.

The study, “Screening for Hepatitis C Virus Infection in Adolescents and Adults,” was published online in JAMA.