Hepatitis C virus (HCV) infection, an underdiagnosed and undertreated multifaceted systemic disease, has a protracted chronic phase with hepatic and extrahepatic manifestations that affects an estimated 3.7 million people in the United States.^1–5 From 2010 to 2018, the incidence of acute HCV infection among people 18 to 39 years of age quadrupled because of the opioid epidemic and the associated increase in people who inject drugs.^1–8 Globally, less than 5% of people with HCV have been diagnosed, and less than 1% have received treatment.^1,6,7

The World Health Organization and the National Academies of Sciences, Engineering, and Medicine have developed strategies to eliminate HCV by 2030.^1,6,7 Strategies include expanded screening, better access to appropriate care, and highly effective direct-acting antiviral medication.^1,6,7 The United States is not on track to meet this goal.^1,4,6,7 Estimates for 2018 indicated that 52% of people in the United States were aware of their disease, and 37% had received treatment.⁴ Current barriers to access and treatment include the asymptomatic nature of chronic HCV, lack of access to specialty care, high cost of treatment, insurance guidelines requiring advanced stages of liver fibrosis before approving therapy, substance use and sobriety requirements, and prescriber restrictions (https://stateofhepc.org/).^1,6–15

Transmission

Injection drug use accounts for approximately 60% of acute HCV infections in the United States.^1,2,8,15 Men who have sex with men (particularly people with HIV or those who have unprotected anal intercourse), perinatal transmission, and exposure to blood products before 1992 are other sources.^2,8,15,16 Nosocomial exposure (e.g., hemodialysis, needlestick) and cosmetic exposure (e.g., tattooing, piercing) are less likely routes of transmission if standard infection-control practices are followed^8,15 (Table 1^2,8,15–18).

Screening

The Centers for Disease Control and Prevention recommends universal HCV screening at least once for all adults 18 years and older and during each pregnancy ¹⁹ (Table 2).¹⁷ The American College of Obstetricians and Gynecologists recommends screening all pregnant individuals during each pregnancy.²⁰ People at risk, or those who request testing, should be screened periodically for as long as the at-risk behavior persists.¹⁷ One-time screening is recommended for patients younger than 18 years with risk factors.¹⁷ The U.S. Preventive Services Task Force recommends screening all asymptomatic adults (including people who are pregnant) 18 to 79 years of age and people younger or older who are at high risk of infection.²¹ Anti-HCV antibody testing (third-generation enzyme-linked immunosorbent assay with 99% sensitivity and specificity) is the screening test of choice with follow-up reflex HCV RNA polymerase chain reaction testing for positive results to confirm the active disease.^8,15,17 Point-of-care testing allows for expanded screening.^8,22 The OraQuick HCV rapid antibody test is a Clinical Laboratory Improvement Amendments–waived point-of-care test with reliable results (sensitivity, 94.1%; specificity, 99.5%; positive predictive value, 72.7%; and negative predictive value, 99.9%).^8,22