In the United States, hepatitis C virus (HCV) remains a major contributor to hepatocellular carcinoma, liver cirrhosis and early mortality despite the availability of curative treatment.^1–5 By 2007, HCV infection had surpassed HIV infection as a cause of death.⁶ This shift reflects the ongoing challenges in HCV infection testing, diagnosis and treatment, alongside improvements in HIV infection management. While steady declines in the national HCV-associated mortality rate were observed in more recent years, disparities have existed differentially across certain sociodemographic groups, with rates consistently at least two times the national average.² The HCV RNA-positivity prevalence during January 2017–March 2020 was approximately .9%, representing 2.2 million people.⁷ Nearly one-third were unaware of their HCV infection.⁷ Before the discovery of HCV in 1988 and the testing of the donor blood supply in 1992, HCV was primarily transmitted via percutaneous exposure to blood during medical procedures or from injection drug use (IDU).⁸

In the United States, HCV infection occurs primarily and efficiently through IDU.^2,9,10 However, transmission occurs in other ways. In 2021, 71% of newly reported acute hepatitis C cases had missing IDU information and 13% did not indicate IDU as a risk behaviour.² In addition to IDU, hepatitis C risk behaviours and exposures reported in 2021 included sexual contact, particularly among men who have sex with men, needlestick injury, household contact, occupational exposure to blood and health care procedures such as surgery, dialysis and transfusion.² Furthermore, HCV transmission can occur through tattoos and piercings performed outside of licensed professional settings from practices that do not adhere to proper hygiene and infection control measures.¹¹ Finally, 199 cases were confirmed and reported as perinatal hepatitis C among children in the United States in 2021, emphasising the importance of universal hepatitis C screening during pregnancy.^2,12

The epidemiology of HCV infection is shifting. Newly reported chronic cases are predominantly among young adults who share injection drug needles and other drug paraphernalia; however, HCV infection prevalence and mortality are highest among people born during 1945–1965, where transmission mainly occurred through other ways.^6,13–15 In 2012, the US Centers for Disease Control and Prevention (CDC) recommended universal HCV screening among this birth cohort to facilitate the diagnosis and linkage to care of people living with HCV infection.¹⁶ Despite the longstanding recommendation, the current HCV infection prevalence was higher among people aged 55–64 years compared to any other adult age group during January 2017–March 2020, suggesting inequitable access to testing and treatment efforts in this age group.⁷ HCV transmission among the 1945–1965 birth cohort could have occurred during the 1960s–1980s through blood transfusions, organ transplants and medical procedures before universal precautions were implemented to prevent transmission of bloodborne pathogens.^17,18 People from this birth cohort with chronic HCV infection have been undiagnosed for decades, increasing their risk for serious liver-related morbidity and mortality. The misconception that people born during 1945–1965 acquired their HCV infection mostly from IDU can be a barrier to testing. Patients can opt out of screening and might be more likely to do so if they believe IDU is the only risk for HCV transmission.

Many interventions and strategies are now available to improve outcomes along the HCV care cascade. In 2014, all-oral direct-acting antiviral agents (DAAs) that can cure ≥95% of people with current HCV infection became available.¹⁹ In the following years, several complementary recommendations were released by national societies and the CDC. Recommendations included (1) the expansion of testing recommendations to include a one-time HCV screening of all adults aged ≥18 years and pregnant people during each pregnancy and (2) simplified treatment guidelines that recommend DAA treatment for all patients with acute or chronic HCV infection.^12,20

Using a US nationally representative sample, we sought to establish the prevalence and measure disparities in HCV infection among people aged 12–59 years who did not report an IDU history. In support of national recommendations for universal HCV screening,¹² this analysis will provide evidence to help public health professionals focus outreach efforts and encourage health care providers to communicate with patients about HCV infection risks.

In this analysis of the non-institutionalised US population aged 12–59 years during January 2013–March 2020, we estimated more than half a million people with no IDU history who have current HCV infection. This finding confirms that many people acquired HCV infection via routes other than drug injection, giving credence to the recent recommendation to expand from risk-based testing to universal screening.¹² Universal HCV screening is a strategy that will help close the gap in identifying individuals who do not disclose risk factors. Additionally, universal HCV screening obviates the need to enquire about risk factors, which might address the stigma associated with HCV infection.

Among people with no drug use history, current HCV infection prevalence rates were higher among people born during 1954–1965 (compared to those born after 1965), had completed a high school education or less (compared to those who completed at least some college) and with past or present hepatitis B (compared to those vaccinated for hepatitis B). These findings might suggest disparities in social factors and the need for strategies that are tailored to the needs of the populations disproportionately impacted. Though IDU is currently the main risk factor for HCV transmission, individuals born during 1954–1965 acquired their HCV infection from additional routes, including blood transfusions, organ transplants and other health care-associated procedures, during the 1960s–1980s before implementation of universal infection control measures for bloodborne pathogens. Hepatitis C testing and treatment costs are covered under Medicare, removing cost-related barriers. Future studies should seek to explore the social determinants of health factors contributing to inequitable access to hepatitis C services among population groups with a higher prevalence of HCV infection. The higher prevalence of HCV infection among individuals who ever had hepatitis B might suggest shared modes of transmission, such as IDU, and underscores the importance of integrated services for multiple conditions, including hepatitis C, hepatitis B and HIV.^2,30

Tailoring hepatitis C public health efforts to disproportionately affected populations and communities is essential for addressing disparities, improving the effectiveness of universal recommendations and enhancing elimination efforts.³¹ Local interventions should consider the unique needs of each community, including barriers to accessing services, provider training in rural and underserved areas and cultural norms. The HCV elimination programme at Cherokee Nation Health Services in Oklahoma embodies this approach.³² In response to the high HCV infection prevalence in American Indian communities, the HCV elimination programme was launched in 2015 and focused on universal HCV screening, primary HCV workforce expansion and harm reduction services.³² Efforts focused on screening anyone who visited the Cherokee health centres, ensuring wide coverage in early identification, treatment and support services. By targeting screening and providing culturally competent care, this initiative has effectively reduced the prevalence of HCV infection in the Cherokee Nation and serves as a model for other tribal health systems.³² Other local and global initiatives using tailored approaches have similarly documented successful reductions in hepatitis C disparities.^31,33

There are several limitations to report. First, stigma associated with drug use might have introduced social desirability, non-response and recall bias in self-reported drug use, potentially resulting in an overestimation of people with no drug use history and an underestimation of people with a drug use history. A sensitivity analysis from a previous NHANES publication assessed selection bias by comparing the distribution of characteristics of participants aged 20–59 years who did and did not respond to the IDU history question during 2001–2016. The analysis concluded that selection bias could not be ruled out.³⁴ To mitigate potential biases, NHANES questionnaires that cover sensitive topics, including drug use, were administered through an audio computer-assisted self-interview in the mobile examination centre.²¹ Despite the potential for bias, NHANES remains the only data source that comprehensively integrates detailed interview and laboratory testing data to produce US population-based HCV infection seroprevalence estimates by drug use status. Second, although NHANES is representative of US households and can produce generalisable findings, these data do not fully represent all people with HCV infection. People experiencing homelessness and people in institutionalised settings, who have disproportionately higher HCV prevalence than the general population, are not included in the NHANES sampling frame.^21,26 Third, this study population was limited to people aged 12–59 years to include all ages for which drug use information during our study period; therefore, we did not capture people born in the oldest Baby Boomer birth cohort (1945–1953) who have a higher prevalence of HCV infection than people in the general population and those born in the younger Baby Boomer years.^13,14,35 Fourth, several prevalence estimates within sociodemographic categories did not meet NCHS standards for presentation due to small sample sizes, which limited our ability to interpret those findings as well as account for potential confounders through multivariable analyses.²⁹ Finally, while we were able to examine socioeconomic factors such as educational attainment and health insurance status, socio-determinants of health factors that are community-based could have contributed to disparities in HCV infection but could not be explored in this analysis due to the lack of geographic identifiers in NHANES data.

In conclusion, we estimated that 1.4 million people aged 12–59 years have a current HCV infection and need treatment, with over half a million people having no IDU history. Among people with current HCV infection and no drug use history, disparities were found among people born during 1954–1965, people with lower educational attainment and people with past/present hepatitis B. This study supports universal HCV screening as a strategy that will help close the gap in identifying individuals who do not disclose risk factors. Utilising quality surveillance and supplementary data sources can more effectively guide and monitor the progress of outreach efforts. To address disparities, efforts at the federal, state and local should focus on tailored approaches to improve equitable access to HCV testing, treatment and preventive services among disproportionately impacted populations.