Introduction

Over 3.2 million people in the USA are chronically infected with hepatitis C virus (HCV) infection [1]. If left untreated, chronic HCV can cause progressive liver fibrosis and cirrhosis, leading to hepatic decompensation and hepatocellular carcinoma [2]. Mortality due to chronic HCV infection has continued to rise in the USA over the last decade, and recent estimates suggest that HCV infection contributes to approximately 20,000 deaths annually [3]. Moreover, death from chronic HCV in this country has now surpassed mortality from more than 60 other nationally notifiable infectious diseases, including human immunodeficiency virus (HIV) infection and tuberculosis [3].

However, all-oral, direct-acting antiviral regimens for the treatment of chronic HCV became available in 2014, resulting in cure of infection in more than 94% of patients with typically no more than 8–12 weeks of treatment and few adverse effects [4•]. The availability of these highly curative therapies offered the potential to reduce the risk of HCV-associated morbidity and mortality, decrease HCV transmission, and eliminate HCV infection as a public health problem [5]. Recognizing the unique opportunity offered by these new antivirals, in June 2016, the World Health Assembly formulated a global action plan to reduce the incidence of HCV infection by 90% and decrease HCV-related mortality by 60% by the year 2030 [6]. Within the US, the Division of Viral Hepatitis of the Centers for Disease Control and Prevention (CDC) sought to establish a formal public health plan that identified specific and measureable HCV elimination goals in the USA that aligned with the global HCV response [7]. To aid in this effort, an independent scientific committee was convened by the National Academies of Sciences, Engineering, and Medicine to identify existing barriers to HCV elimination in the USA, formulate recommendations to overcome these challenges, and propose feasible elimination targets by 2030. An initial report evaluating the feasibility of HCV elimination in the USA and barriers to achieving this goal was released in April 2016 [8••]. A subsequent report formulating recommendations to achieve HCV elimination targets by 2030 was published in March 2017 [9••]. This latter report proposed ways to improve adherence to each step of the HCV care continuum and constitutes the framework for a national strategy to eliminate HCV infection in this country.

This review summarizes the recommendations to achieve HCV elimination in the USA made by the National Academies committee. These recommendations are grouped into four broad categories corresponding to the key HCV elimination goals: (1) increasing HCV screening, diagnosis, and linkage into care; (2) decreasing HCV-related morbidity and mortality; (3) reducing HCV incidence; and (4) improving national HCV surveillance (see Fig. 1).

Fig. 1
figure 1

Four main categories of national hepatitis C virus elimination goals recommended by the National Academies of Sciences, Engineering, and Medicine and strategies to achieve these goals

Full size image

Increasing HCV Screening, Diagnosis, and Linkage To Care

Identify Settings for Enhanced HCV Testing Based on Expected Prevalence

To date, the CDC and US Preventive Services Task Force have recommended targeted HCV screening in groups with HCV prevalence higher than that of the general population [10, 11]. However, approximately half of chronic HCV-infected patients in the USA remain unaware of their diagnosis, representing the largest drop-off in the HCV care continuum [12•]. Challenges to HCV diagnosis include the reluctance of patients to report risk behaviors, frequent absence of symptoms associated with chronic infection, and low adherence to HCV screening by providers in clinical practice [8••, 12•]. Diagnosis of HCV infection has been particularly hampered by a lack of prioritization of screening among primary care providers due to competing clinical demands, limited staff time, and discomfort with discussing high-risk behaviors with patients [13, 14]. Recognizing that improving rates of HCV diagnosis will be critical for HCV elimination efforts, the National Academies’ report recommended that the CDC work in conjunction with state and local partners to identify high-risk settings for enhanced HCV testing [9••]. Given that persons with chronic HCV infection may not routinely engage in medical care, HCV screening efforts also will need to be expanded into community-based venues.

Emergency departments may be a potentially high HCV prevalence setting in which to screen for HCV infection. Within 6 months of implementing an HCV testing program at an urban emergency department in the Alameda Health System in Oakland, CA, investigators found a 10% prevalence of HCV antibody-positivity among screened patients [15]. HCV screening did not increase median emergency department length of stay compared to patients undergoing other laboratory testing, supporting the feasibility of integrating HCV screening in this setting [15]. Another study that implemented the CDC’s targeted, risk-based HCV screening guidelines in the Johns Hopkins Hospital Emergency Department in Baltimore, MD found a 13.8% prevalence of HCV antibody-positivity and reported that 31% of identified infections were newly diagnosed [16]. The study also demonstrated that one-quarter of infections would have gone undiagnosed if current CDC birth cohort recommendations were employed, suggesting that in high-risk urban emergency department settings, a practice of universal one-time HCV testing might be effective to diagnose HCV infection [16].

HCV screening initiatives have been implemented in other high HCV prevalence settings. The “Test, Listen, Cure” Hepatitis C Community Awareness Campaign (HepTLC), funded by the CDC, supported HCV testing at sites providing care to people who inject drugs (PWID), including needle/syringe service programs, Ryan White-funded clinics, sexually transmitted infection clinics, and local and state health departments [17]. Between 2012 and 2014, 15,274 PWID were screened, of whom 23% tested positive for HCV antibody, illustrating this program’s successful outreach to a high-risk group. Another effective HCV screening program used a mobile medical unit and patient navigator services to reach patients outside of traditional clinical settings [18]. Participants were recruited by door-to-door outreach and at community events. In the mobile unit, all participants underwent rapid HCV testing and, if positive, confirmatory HCV RNA. Patient navigators provided counseling about test results and facilitated linkage to follow-up HCV care for those found to be HCV RNA-positive. In the first 16 months of this project, 1301 participants were tested, and the prevalence of HCV antibody-positivity was 3.9%. Efforts such as these might be particularly valuable at identifying HCV-infected individuals who do not have frequent contact with the health care system.

Innovative public health-academic partnerships also may be valuable at improving HCV screening and can combine the technical and clinical expertise of an academic institution with the strong local engagement of a community organization to ensure thorough follow-up for newly identified chronic HCV-infected patients. In one such partnership, collaborators at Johns Hopkins University School of Medicine engaged with a community organization in Baltimore, MD called Sisters Together and Reaching (STAR), Inc. to screen PWID at community events, drug treatment centers, and homeless shelters [19]. This effort led to the identification of 49 (15%; n = 325) HCV antibody-positive individuals. Case management personnel worked to confirm chronic HCV infection, obtain health insurance (if not previously acquired), facilitate referral for HCV treatment, and ensure adherence to medical visits [19].

Continued efforts aimed at enhancing HCV screening in settings of expected high prevalence and potentially outside of traditional healthcare venues will be needed to increase the proportion of patients who are diagnosed, linked to care, and treated, which ultimately will be crucial for the success of the US HCV elimination strategy.

Establish Measures to Monitor Adherence to HCV Screening

Attempts to improve adherence to HCV screening guidelines have primarily focused on simplification of screening recommendations and educational interventions but have not been shown to have substantial impact. Recognizing that the complexity of the CDC’s 1998 HCV screening guidelines contributed to low implementation rates [20], simplified guidelines were published in 2012 [10], but HCV screening has remained poor [21, 22]. One study that provided continuous, educational sessions about HCV testing guidelines to primary care clinics over a 15-week period found that adherence to screening actually decreased over time [13].

Given the limitations of existing interventions in improving HCV screening, alternative strategies, such as direct performance evaluation of adherence to viral hepatitis testing and linkage to care, may be effective at improving provider adherence to HCV screening guidelines. The National Committee for Quality Assurance seeks to ensure that recommendations for improving health are implemented in clinical practice and monitors the adherence of these recommendations within health plans. Adding viral hepatitis measures to the Healthcare Effectiveness Data and Information Set may increase the priority of HCV screening by insurers and healthcare providers. Accordingly, the National Academies’ report recommended that the National Committee for Quality Assurance should establish measures to monitor compliance with viral hepatitis screening guidelines [9••].

Increase Support for Hepatitis Case Finding and Linkage to Care

Timely diagnosis of chronic HCV infection and appropriate linkage to care are critical for HCV elimination efforts but have been hampered by inadequate resources within local health departments [23]. The National Academies’ report recommended that the CDC should work with local partners to support standard hepatitis case finding measures and facilitate linkage of all HCV-infected patients into care [9••]. Existing cooperative agreements between each state and the CDC’s Epidemiology and Laboratory Capacity for Infectious Diseases may provide a mechanism for further funding and capacity building around HCV surveillance and follow-up [9••, 24]. This additional funding could be used to support expanded staff resources, build informatics systems, and develop crosswalks between public health systems and electronic health records. The Massachusetts Department of Health and the Harvard Center for Excellence in Public Health Informatics have already collaborated to develop an automated HCV detection and reporting system that extracts relevant data from patients’ electronic health records, applies HCV detection algorithms, and sends potentially new cases of HCV infection to health departments for further investigation [25]. The program is publicly available and compatible with different electronic medical record systems, expanding its utility and reach across clinical practices in the state [9••, 25].

Decreasing HCV-Related Morbidity and Mortality

Expand the Number of HCV Providers

Mathematical modeling analyses within the National Academies’ report estimated that at least 260,000 chronic HCV-infected patients must be treated yearly to achieve elimination of HCV in the USA by 2030 [9••]. As a result, successful HCV treatment scale-up will require expansion of HCV provider capacity. In the interferon era, HCV treatment was primarily coordinated by hepatologists and infectious diseases specialists in office settings with established resources for administering complicated treatment regimens and managing the side effects of antiviral therapy. However, the ease of administering new DAA regimens that are all-oral, well-tolerated, and require short treatment duration has made HCV treatment feasible by non-specialist providers in a variety of settings [26,27,28,29]. In particular, strategies to offer HCV care in the primary care setting may mitigate the drop-offs in linkage to care that occur with subspecialty referral [18]. Consequently, the National Academies’ report proposed that the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America partner with primary care providers and their professional organizations to build capacity to treat chronic HCV infection in the primary care setting [9••]. Capacity building in primary care will require not only one-time training conferences but also standing programs between primary care providers and specialists.

Pilot partnerships have already demonstrated the feasibility of expanding HCV treatment to non-specialist health providers. For example, in the Extension for Community Health Care Outcomes (ECHO) program, the CDC and the University of New Mexico collaborated to build a program that trained primary care physicians in Utah and Arizona, using videoconferencing and case-based learning tools to treat chronic HCV in rural settings with limited access to specialist care [27]. As an additional example, the New York City Department of Health and Mental Hygiene has developed networks to provide educational resources, access to HCV treatment guidelines, and mentoring and consultations for providers managing patients with chronic HCV [28]. Finally, in California, a task-shifting treatment model for HCV was implemented that enabled a trained licensed practical nurse, under the guidance of hepatologists, to treat over 100 HCV-infected patients between 2014 and 2015 [29]. A secure web-based electronic health record enabled the nurse to communicate with hepatologists for medical advice as needed. These reports demonstrate the feasibility of programs aimed at expanding the pool of providers for HCV care and treatment.

Increase HCV Screening and Treatment in Correctional Settings

HCV infection is common in prison and jail settings, with an estimated prevalence of 12–35% [30]. Given that more than 90% of these persons are released and typically have little subsequent contact with the healthcare system, correctional institutions represent valuable settings in which to reduce HCV-related morbidity and mortality. They could offer access to HCV providers—either directly on staff or via telemedicine—to facilitate evaluation and treatment of HCV infection. There is also the opportunity for directly observed therapy in this setting, minimizing the risk of antiviral drug diversion. However, few correctional facilities have formal HCV screening and treatment guidelines [31, 32]. To reduce HCV-associated morbidity, the National Academies’ report recommended that correctional settings should be a focus of HCV screening and treatment efforts [9••]. In support of this recommendation, mathematical model analyses have suggested that strategies for opt-out HCV screening and DAA treatment in the prison setting would be highly cost-effective from a societal perspective [33, 34].

Establish a System to Support Key Populations with Chronic HCV

The high prevalence of chronic HCV infection among marginalized populations, including PWID, homeless, and incarcerated persons, has complicated efforts aimed at HCV diagnosis, linkage to care, and treatment. As a result, the National Academies’ report recommended that the Department of Health and Human Services should work with states to build a comprehensive system of care and support for these key populations with chronic HCV on the scale of the Ryan White system [9••]. The Ryan White HIV/AIDS Program has ensured access to preventive and treatment services for people living with HIV/AIDS in the USA since 1990 [35, 36]. Ryan White programs also offer case management, mental health services, and substance use treatment for their clients, all of which are critical components of care for HCV-infected individuals [35]. Given the overlap in risk factors for HIV and HCV, it might be feasible to expand existing Ryan White programs to offer outreach services for patients with chronic HCV infection, regardless of HIV status. Notably, 29 states have provided HCV treatment for HIV/HCV-coinfected patients through the Ryan White program since 2011 [37]. By providing a safety net for key vulnerable groups who may be underinsured or uninsured, such a comprehensive system of care and support could help to reduce HCV-related morbidity and mortality and greatly aid national HCV elimination efforts.

Remove Restrictions to DAAs and Increase Access to HCV Therapy

The costs of DAAs led public and private insurers in the USA to restrict access to these medications [38]. Insurers established varying criteria for reimbursement of DAAs, such as evidence of advanced liver fibrosis, consultation with a specialist, and/or abstinence from alcohol or illicit drug use [39, 40]. Restrictions for reimbursement of DAAs have been shown to be common across state Medicaid programs [41,42,43]. Criteria for approval of DAAs in Medicare and commercial insurance health plans have not been reported. Analyses conducted shortly after the release of DAAs into the market showed that the downstream effect of these restrictions was to make common the denial of reimbursement of DAA treatment by insurers [44, 45].

The high incidence of denial of DAA therapy by insurers has important implications. From a clinical standpoint, patients denied access to HCV therapy remain at risk for the development of hepatic fibrosis, cirrhosis, liver decompensation, and hepatocellular carcinoma [46••]. Denial of DAA treatment can also lead to ongoing HCV-associated inflammation, which might increase the risk of extra-hepatic complications [47, 48]. Further, failure to treat and cure chronic HCV maintains a reservoir of HCV transmission. From a public health standpoint, the high incidence of denial of DAA treatment represents a major barrier to the goal of HCV elimination. Viral eradication can help to eliminate HCV transmission [49, 50], reduce the risk of liver complications [51], decrease extra-hepatic manifestations [52], and prolong survival [53]. DAA treatment has also been shown to be cost-effective [54,55,56]. The ability to cure chronic HCV in nearly all infected people makes the prospect of eliminating HCV infection in the USA feasible [26]. As a result, the National Academies’ report recommended that public and private insurers should remove restrictions to DAAs that are not medically indicated and offer treatment to all chronic HCV-infected patients [9••]. This recommendation is consistent with guidelines from the American Association for the Study of Liver Diseases/Infectious Diseases Society of America that recommend DAA treatment for all patients with chronic HCV infection [46••].

Given the costs of DAA drugs, alternative means of financing these therapies may need to be considered. The National Academies’ report provided several alternative proposals for financing HCV elimination [9••]. One proposal suggested that the federal government, on behalf of the Department of Health and Human Services, could consider purchasing the rights to a DAA for use in neglected market segments, such as state Medicaid programs, the Indian Health Service, and correctional settings. In such a scenario, the government would acquire the licensing rights to a DAA patent in a voluntary transaction with a pharmaceutical company for use of that drug in these neglected sectors. Such a licensing strategy would allow the government to control costs while negotiating reasonable compensation for drug companies. Although the initial investment for the federal government would be large, the long-term cost savings could be considerable and would allow many patients to be treated [9••]. Alternative strategies to address the costs of DAA treatments might include seeking discounts for bulk or pooled purchases [57, 58] or obtaining DAA regimens through the 340B Drug Discount Program, which provides medications at greatly discounted prices to safety net providers caring for uninsured or low-income patients [59].

Reducing HCV Incidence

Expand Access to Needle/Syringe Services and Opioid Agonist Therapy

Since injection drug use is the predominant mode of HCV transmission in the USA, prevention efforts among PWID must be a priority in order to reduce HCV incidence [60•]. Harm reduction services, which include needle/syringe exchange programs and opioid agonist therapy (OAT), have been shown to have significant impact as HCV prevention strategies. However, their utilization remains low due to restrictive policies and barriers to PWID outreach [60•, 61]. Consequently, the National Academies’ report recommended that states and federal agencies should expand access to needle/syringe exchanges and OAT in accessible venues [9••].

Numerous studies have demonstrated that needle/syringe service programs can lead to long-lasting changes in injecting risk behaviors among PWID, including sharing of needles, syringes, or other injection drug paraphernalia [62,63,64,65]. Several studies have found a lower prevalence and/or incidence of HCV infection among PWID participating in needle/syringe exchange programs compared to those who do not [62, 66, 67]. A cohort study of PWID in the Netherlands found that participants who received full harm reduction services, defined as obtaining all needles/syringes from an exchange program along with daily OAT, had a substantially lower incidence of HCV infection compared to those receiving no harm reduction services (incidence rate ratio, 0.15; 95% CI, 0.06–0.40) [66]. In addition, in one systematic review, needle/syringe service programs were associated with significant decreases in HIV and HCV prevalence [62].

While the number of needle/syringe exchange programs in the USA has grown over time, there remains an insufficient number and disparate distribution of these programs across the country to meet the demands of the PWID population [9••, 68, 69]. Pharmacies, often conveniently located throughout communities and with long hours of operation, represent a viable resource to address the lack of needle/syringe service programs. Pharmacies could provide nonprescription sale of sterile needles/syringes, which has been shown to successfully reduce HIV transmission [70]. While all states permit sale of needles/syringes without prescriptions, there are varying levels of restrictions imposed by states that would need to be re-evaluated to make pharmacies a source of sterile needles/syringes for PWID [70].

In addition to needle/syringe service programs, OAT can have a direct and lasting impact on reducing the overall incidence of HCV infection among PWID. Epidemiological studies show that by enabling PWID to refrain from HCV-related high-risk behaviors, OAT can reduce HCV incidence and prevent HCV transmission [71,72,73,74]. Further, long-term medication management with OAT is associated with retention in treatment, reduction in illicit drug use, and recovery from opioid dependence/abuse [75, 76].

Despite the benefits of OAT, the availability of these services is lagging far behind the growing demand, particularly in rural areas of the USA [77,78,79]. A recent analysis of the geographic distribution of physicians authorized to prescribe buprenorphine as of 2012 found that 42% of all physicians with waivers were psychiatrists who practiced primarily in urban settings, while only 3% were primary care physicians [77]. As a result, it is estimated that more than 30 million Americans are living in counties without access to buprenorphine treatment [77]. Expansion of telehealth services may be a viable approach to increase access to behavioral health and addiction specialists in remote areas that currently lack these resources or the infrastructure to expand addiction treatment services [80]. Given the coexistence of the opioid and HCV epidemics in the USA, leveraging state and federal resources committed to the opioid epidemic toward HCV prevention and treatment will be crucial to halt ongoing HCV transmission.

Improving HCV Surveillance

Support Studies to Measure HCV Incidence/Prevalence in High-Risk Groups

Surveillance of HCV infection is critically important for assessing all steps along the HCV care continuum, including estimating HCV prevalence and new infections, determining the incidence of HCV-associated liver complications, and evaluating linkage to HCV care and DAA treatment. Current estimates of HCV incidence and prevalence are drawn from data collected through household surveys, electronic healthcare databases, and laboratory reporting, often without a focus on the subpopulations disproportionately affected by HCV infection [81]. For example, the most recent National Health and Nutrition Examination Survey (NHANES) report on the prevalence of chronic HCV found that approximately 2.7 million people are chronically infected with HCV in the USA, but this survey excluded homeless, institutionalized, and incarcerated persons, who are at high risk for HCV infection [1]. There are estimated to be an additional 800,000 (range, 300,000–1.5 million) persons with chronic HCV among these high-risk groups based on extrapolations from HCV seroprevalence studies conducted in those populations [81]. The lack of reliable data on HCV prevalence and incidence in these groups limits the ability of public health and medical professionals to establish and advocate for treatment priorities, resource needs, and goals. As a result, the National Academies’ report recommended that the CDC should support cross-sectional and cohort studies in these high-risk populations to measure HCV prevalence and incidence [9••]. Periodic cross-sectional surveys of high-risk populations would provide more accurate estimates of HCV prevalence over time. Cohort studies of similar populations would enhance our understanding of HCV incidence in these groups. Such studies would complement information about HCV infection coming from population-based surveys such as NHANES.

Expand Hepatitis Testing and Case Finding Based on Prevalence

Strengthening HCV surveillance nationally will require a two-pronged approach: (1) allocation of resources to local and state health department to support HCV testing and linkage to care; and (2) expansion of HCV screening and testing in high-risk settings. To meet these needs, the National Academies’ report recommended that the CDC partner with state and local health departments to support standardization of HCV case finding and follow-up [9••].

HCV disease reporting and case follow-up vary across states, which limits the quality of surveillance data available locally and subsequently shared with the CDC. Automated sharing of positive HCV antibody and/or HCV RNA test results from diagnostic laboratories has improved HCV reporting, but may not provide relevant clinical data to support case finding investigations. Investment in informatics infrastructure may take advantage of widespread use of electronic health records to support HCV surveillance systems [9••]. Further, standardization of disease reporting across states could improve efficiency and work flow within local health departments that continually face resource limitations. These improvements could then support infrastructure investment and expansion of enhanced surveillance to other high-risk settings.

Need For a Central HCV Elimination Coordinating Office

All of the HCV elimination efforts discussed above will require cooperation among federal and state agencies, legislators, health care providers, and professional societies. Leadership from a single office would increase logistical efficiency in implementing these recommendations. Prior examples of successful elimination efforts, including polio, measles, and guinea worm, benefitted immensely from strong political engagement and central coordination at the highest levels of government. Therefore, the National Academies’ report proposed that the federal government should oversee a coordinated effort to manage HCV elimination [9••]. Such an effort could take the shape of a central coordinating office dedicated to viral hepatitis elimination that is located in the White House, similar to the White House Office of National AIDS Policy [82]. Alternatively, the coordinating effort could be undertaken by that office, given its proven expertise working with other federal and state agencies to implement national HIV/AIDS policies. The executive authority afforded to a central coordinating office could support HCV elimination efforts in ways not possible at lower levels of government or by public health organizations.

Conclusions

The potential elimination of HCV infection as a public health threat in the USA was not conceivable among scientific, medical, or public health professionals a decade ago. However, advances in HCV treatment, along with rising HCV incidence due to the opioid epidemic in the USA, have created urgency among these communities to address this previously neglected condition. In response, the National Academies of Sciences, Engineering, and Medicine issued two seminal reports in 2016 and 2017 that highlighted the feasibility of HCV elimination in the USA and proposed evidence-based recommendations to overcome existing barriers and achieve HCV elimination as a public health problem by 2030 [8••, 9••]. These recommendations were aimed at increasing HCV diagnosis and linkage to care, decreasing HCV-related disease burden by scaling up DAA-based HCV treatment, reducing HCV transmission among high-risk groups, and building disease surveillance to assess achievement of elimination targets over time. Given the need for collaboration among stakeholders, a central coordinating office would provide logistical efficiency in supporting these recommendations and ensure successful implementation of the US HCV elimination strategy. Only through such coordinated collaboration will the elimination of HCV infection be not only aspirational, but truly attainable.