Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

From 2013 to 2016, approximately 1.4 million people in the United States had active infection of hepatitis C virus (HCV). It is estimated that people born between 1945 and 1965 make up approximately three-quarters of HCV infections. Therefore, in 2013, the US Preventive Services Task Force (USPSTF) recommended HCV screening for adults born between 1945 and 1965 (birth cohort screening) and those at high risk of infection. This recommendation was based on the effectiveness of antiviral therapies with interferon. Since then, HCV treatment now includes direct-acting antiviral (DAA) regimens without interferon. The aim of this study was to update the 2013 review on HCV screening to inform the USPSTF. A systematic search of the literature in Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Review, as well as continued surveillance, was conducted from 2013 to September 20, 2019. The search criteria included randomized clinical trials (RCTs) and nonrandomized treatment studies of HCV screening and DAA therapy, plus cohort studies on screening, antiviral therapy, hepatocellular carcinoma and cirrhosis, and sustained virologic response (SVR) after antiviral therapy and clinical outcomes. Outcomes were mortality, morbidity, quality of life, HCV transmission, SVR, screening and treatment harms, and screening yield. Exclusion criteria included studies that focused on people with HCV and human immunodeficiency virus or hepatitis B virus, those receiving transplants, and people with active kidney disease. The studies that met the eligibility criteria included 8 RCTs, 48 nonrandomized treatment studies, and 33 cohort studies (n = 179,230 patients). None of the studies evaluated the effects of screening versus no screening. One new study found that perfectly applying risk-based guidelines would identify 82% of HCV cases (number needed to screen to identify 1 HCV case = 14.6). Perfectly screening the birth cohort, in contrast, would identify 76% of HCV cases (number needed to screen = 28.7). Small, short-term improvements in the quality-of-life scores after DAA therapy versus before DAA therapy were reported in 10 studies. One cohort study found that DAA therapy was associated with decreased risk of cardiovascular events compared with interferon-based therapy or antiviral therapy. Two cohort studies were inconsistent in their findings for associations of antiviral therapy versus no therapy and risk of hepatocellular carcinoma. Pooled SVR rates with DAA therapy ranged from 95.5% to 98.9% across genotypes. Harms of DAA therapy included low, short-term rates of serious adverse events and withdrawal due to adverse events (1.9% [95% CI, 68.0% 78.1%]; 0.4% [95% CI, 0.3% 0.6%]). Compared with no SVR, SVR after antiviral therapy was associated with decreased risk of all-cause mortality, as well as hepatocellular carcinoma (13 studies, n = 36,986; pooled hazard ratio [HR], 0.40 [95% CI, 0.28 0.56], and 20 studies, n = 84,491; pooled HR, 0.29 [95% CI, 0.23 0.38], respectively). In conclusion, evidence supporting HCV screening to improve clinical outcomes remains unavailable. However, DAA therapy was associated with high SVR rates (>95%) and few short-term harms. Compared with no SVR, SVR after antiviral therapy was associated with improved outcomes.