BACKGROUND

Prior reviews on hepatitis C (HCV) infection screening and treatment used by the U.S. Preventive Services Task Force (USPSTF) to inform its 2013 recommendation found interferon-containing antiviral therapies associated with sustained virologic response (SVR) rates of 68 percent to 78 percent and an association between SVR after antiviral therapy and improved clinical outcomes. Interferon-containing regimens were associated with a high rate of harms. Since the prior reviews, interferon-containing antiviral therapies have been replaced by all-oral direct acting antiviral (DAA) regimens.

PURPOSE

To systematically review the evidence on screening for HCV infection in asymptomatic adults and adolescents, including effects of DAA regimens and interventions to prevent mother-to-child transmission.

DATA SOURCES

We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Ovid MEDLINE and ClinicalTrials.gov through February 2019, manually reviewed reference lists, and conducted literature surveillance through November 22, 2019.

STUDY SELECTION

Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening.

DATA EXTRACTION

One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

DATA SYNTHESIS (RESULTS): No study evaluated the benefits of HCV screening versus no screening, or the yield of repeat versus one-time screening. Previously reviewed studies found that HCV screening might be associated with negative psychological and social consequences, but had important methodological limitations; no new studies were identified. One new study found similar diagnostic yield of risk-based and birth cohort screening, but it was retrospective and assumed perfect implementation of risk-based screening. Ten trials reported improvements in some quality of life and functional outcomes following DAA treatment compared with prior to treatment, but differences were small, studies were open-label, and there was no non-DAA comparison group. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5 percent to 98.9 percent across genotypes; rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%) were low. Seven trials reported SVR rates in adolescents with DAA therapy similar to those observed in adults. An SVR after antiviral therapy was associated with decreased risk of all-cause mortality (13 studies, pooled hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.28 to 0.56), liver mortality (4 studies, pooled HR 0.11, 95% CI, 0.04 to 0.27), cirrhosis (4 cohorts in 3 studies, pooled HR 0.36, 95% CI, 0.33 to 0.40), and hepatocellular carcinoma (20 studies, pooled HR 0.29, 95% CI, 0.23 to 0.38) versus no SVR, after adjustment for potential confounders. New evidence on interventions to reduce the risk of mother-to-infant transmission was limited and did not change the conclusion from the prior review that no intervention has been clearly demonstrated to reduce risk.

LIMITATIONS

Most DAA trials were not randomized and did not have a non-DAA comparison group, almost all DAA trials relied on SVR as the main efficacy outcome, observational studies varied in how well they adjusted for confounders, and few studies evaluated the effectiveness of DAA regimens in adolescents.

CONCLUSIONS

The USPSTF previously determined that HCV screening is highly accurate. Currently recommended all-oral DAA regimens are associated with very high SVR rates (95.5% to 98.9% across genotypes) and few harms relative to older antiviral therapies. An SVR after antiviral therapy is associated with improved clinical outcomes compared with no SVR, after adjusting for potential confounders. Direct evidence on the benefits of HCV screening remains unavailable, and direct evidence on the effects of antiviral therapy on clinical outcomes remains limited but indicates improved long-term outcomes.