Hepatitis C Virus in Rural America: Tackling a Silent Epidemic

Despite advances in treatment, hepatitis C virus (HCV) infection remains a major health problem worldwide.1 In the United States, rural communities are disproportionately affected by HCV, with rates of infection estimated to be twice as those seen in urban areas and attributed to high rates of injectable drug use among young people.2 Although HCV infection has reached epidemic proportions in younger individuals, those in the Baby Boomer generation remain at increased risk for this disease.3

Complicating things further is the silent nature of the infection; early signs and symptoms do not appear in approximately 80% of individuals.7 Once diagnosed, patients from rural communities frequently face obstacles to treatment, such as lack of resources and trained medical professionals.1 However, research has shown that compared with patients from metropolitan areas, rural patients respond comparably well to treatment with direct-acting antivirals (DAAs), and there is no significant difference in post-sustained virologic response (SVR) expenditures between rural and metropolitan patients.8
Stuart C. Gordon, MD, professor of medicine at Wayne State University School of Medicine and director of hepatology for Henry Ford Health Systems, and Laura Tenner, MD, MPH, associate professor at the University of Texas Health San Antonio MD Anderson Cancer Center and co-director of pharmacy and therapeutics, and ASCO Government Relations Committee member, discuss challenges associated with HCV management in rural America.

Why is diagnosing HCV infection more challenging in rural communities than in urban communities?

Stuart Gordon, MD: Both acute and chronic HCV infections are usually asymptomatic; therefore, it is especially challenging to diagnose this condition in rural America, where access to routine health care — much less, HCV screening — is limited. Moreover, most HCV carriers in rural communities are younger adults (owing to recent drug use)9; in the absence of symptoms or abnormal liver enzymes that would trigger viral hepatitis screening, these young adults remain undiagnosed. Once diagnosed, residents of rural communities face additional obstacles to receipt of care, including long driving distances to providers able to help them. A recent US Preventive Services Task Force recommendation to 1-time screen all US adults for anti-HCV may help to identify large segments of rural America carrying this virus. But their linkage to care remains challenging. 

How effective are the current therapies for HCV infection, and are they accessible to patients in rural communities?

Dr Gordon: The therapy for HCV infection is simple and is nearly 100% effective at eradicating virus. There rarely is a contraindication to treating and curing all infected individuals. Such treatment (1) halts injury to the liver that can result in liver scarring, cirrhosis, and increased risk of liver cancer; (2) prevents downstream HCV-mediated extrahepatic disease, such as diabetes and cardiovascular disease; and (3) prevents transmission to others.  Recent American Association for the Study of Liver Disease guidelines vastly simplify how to assess liver disease severity such that all treating providers, including family practitioners and mid-level clinicians, can confidently initiate such treatment. Accessibility of such cures — especially for patients in rural communities — may be limited by insurance or state Medicaid requirements for treatment to be managed by specialty physicians who do not practice in rural areas and insurance denial of such treatment if the patient has a substance use disorder. Each limitation to access to therapy represents an obstacle to curative therapy that does not exist for other medical conditions. Stephens et al showed that there is no significant difference in sustained response/treatment failure rates between rural and metropolitan-area patients,8 nor was there a significant difference in post-SVR expenditures between rural and metropolitan-area patients.

Why is HCV treatment access lower in rural communities, and how can it be improved?

Dr Gordon: The seroprevalence of HCV among persons who inject drugs is >50%. A recent study among rural Appalachian people who use drugs showed that nearly 60% of patients contacted a healthcare provider shortly after learning of their HCV-positive status, but only 8% actually received treatment. These results suggest that most barriers to receiving treatment are “further downstream.” There remains the perceptions (on the part of patients) that such treatment is arduous and (on the part of providers) that treatment requires special skills that are beyond their expertise.  Using modeling, Fraser et al showed that reducing HCV incidence and providing treatment in these rural areas were achievable when accompanied by medication-assisted treatment and effective syringe service programs.9 This model showed that numbers of people who inject drugs (PWID) in rural areas without such programs will be associated with increases in new HCV infections, whereas established harm-reduction programs in urban areas have already resulted in stable or decreasing new HCV infections. Optimizing harm-reduction programs in both rural and urban areas, including targeted DAA treatment for HCV-positive PWID, could result in significant reduction in prevalence of chronic HCV among PWID by 2030.

What still needs to be done to improve the care of individuals with HCV in rural America? Are you aware of any state or national programs that are working to address this need?

Dr Gordon: Surprisingly, some state Medicaid systems prevent their citizens from accessing curative treatment by creating artificial barriers. The Hepatitis C State of Medicaid Access project is overseen by the Center for Health Law and Policy Innovation of Harvard Law School and the National Viral Hepatitis Roundtable.  State-by-state “report cards” detail limitations to the access to lifesaving therapy and outline the potentially fatal consequences of such barriers to access.  For example, as of [August 2021], New York and Louisiana get an “A+,” while South Dakota and Arkansas get an “F.”
Liver damage restrictions (ie, covering treatment only if liver fibrosis has already developed, as defined indirectly by biomarkers), prescriber restrictions (ie, allowing only specialists, who are rarely available in rural areas, to treat), and sobriety restrictions (which is not a barrier for receipt of treatment for other infectious diseases) all inflict particular hardship on rural Americans with chronic HCV infection. The Hepatitis C State of Medicaid Access project offers a “take action” petition that provides individuals the ability to speak up and spread the word about individual difficulty accessing HCV treatment.

Please tell us about the main goals of the National Academies of Sciences, Engineering, and Medicine strategy aimed to decrease the prevalence of HCV by 2030. How will it affect rural communities in particular?

Laura Tenner, MD, MPH: The consensus committee of the National Academies of Sciences, Engineering, and Medicine produced 2 reports: the first outlines the obstacles to eradicating hepatitis B virus (HBV) and HCV infections in the United States and the second delineates the steps needed to overcome these obstacles and achieve this goal.12,13 The second report identified 5 areas for improvement: information, interventions, service delivery, financing, and research. The report outlined a need for more complete information on the incidence, prevalence, and care delivery patterns of HCV and HBV to inform interventions for prevention and treatment. Because the healthcare system does not always touch the populations in rural communities or with higher prevalence of disease, service delivery and financial toxicity were a focus of the report. The specific recommendation identified by the committee for rural communities and the underserved was to try to expand HCV prevention, diagnosis, and treatment to the primary care clinics and move away from the limitation of requiring specialists, who tend to be focused in urban areas and can present cost limitations. And, finally, the report concluded that research in all areas, from vaccine development to new diagnostic technologies to population studies, should be expanded.

HCV in Rural America: Tackling a Silent Epidemic Table 1
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Which barriers to HCV care have been identified in rural Texas?

Dr Tenner: This population tends to be more impoverished, have less healthcare coverage, and to be less educated with low rates of healthcare literacy.14 Transportation is a significant barrier secondary to the cost of maintaining a vehicle and the distances needed to travel for care. Public transportation is limited in these areas as well.15 For those patients who have health insurance coverage, copayments for these oral medications may be limiting access to treatment. These medications can range from $40,000 to $80,000 for a full course of therapy, with most insurers requiring some form of cost sharing from patients, sometimes as much as 20% to 40%. For patients without insurance and who are impoverished, they may be able to get free drug through the pharmaceutical medication assistance programs but are unable to pay for physician visits and transportation costs.16

What is the long-term health benefit to patients and the economic impact on the community of eradicating HCV infection? Why should this be a priority?

Dr Tenner: The long-term benefit to patients who are treated for HCV is a decrease in rates of liver failure, liver cirrhosis, cancer, and death. That being said, programs have focused only on treating patients who have already developed severe liver cirrhosis, which limits the individual benefits from these very expensive treatments. Through earlier treatment, extensive damage to the liver can be avoided, and the patient will be less likely to develop cancer or fulminant liver failure, thereby avoiding significant downstream costs.13,16,17 The average cost of liver transplantation is approximately $300,000, and that does not include the cost of hospitalizations for symptomatic treatment of the side effects of end-stage liver disease. If cancer develops, the cost rises substantially.
One benefit associated with early treatment of HCV that is often overlooked is that the pool of infected individuals who could potentially spread the virus decreases as well.16,17 As individuals are treated early in their disease course, the likelihood of them passing on the virus to other individuals decreases, thereby having significant downstream cost savings and moving us closer to eradicating the disease.7,10,11
This must become a priority for Texas as well as the nation as liver cancer death rates continue to rise, as does the cost of health care.

Long-term benefits of HCV eradication
Long-term benefits include reduced hepatic fibrosis, lower risk of developing hepatic failure, decreased occurrence of hepatocellular carcinoma, and improved survival.


Stuart Gordon, MD, reported affiliations with Gilead Sciences, Inc., and AbbVie, Inc.  Laura Tenner, MD, MPH, reported affiliations with New Beta Innovation, Ltd., Bayer, and Community First Health Plans.


1. Tahan V, Almashhrawi A, Kahveci AM, Mutrux R, Ibdah JA. Extension for community health outcomes – hepatitis C: small steps carve big footprints in the allocation of scare resources for hepatitis C virus treatment to remote developing areas. World J Hepatol. 2016;8(11):509-512. doi:10.4254/wjh.v8.i11.509
2. Suryaprasad AG, White JZ, Xu F, et al. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012. Clin Infect Dis. 2014;59(10):1411-1419. doi:10.1093/cid/ciu643
3. Gordon SC. Hepatitis C virus detection and treatment in rural communities. Gastroenterol Hepatol. 2018;14(12):720-722.
4. November 6, 2018 – CDC estimates nearly 2.4 million Americans living with hepatitis C. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchhstp/newsroom/2018/hepatitis-c-prevalence-estimates.html. Updated November 6, 2018. Accessed September 21, 2020.
5. Yehia BR, Schranz AJ, Umscheid CA, Re III VL. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):e101554. doi:10.1371/journal.pone.0101554
6. Viral hepatitis surveillance report 2018 — Hepatitis C. Centers for Disease Control and Prevention website. https://www.cdc.gov/hepatitis/statistics/2018surveillance/HepC.htm. Updated August 28, 2020. Accessed September 21, 2020.
7. Stephens DB, Young AM, Havens JR. Healthcare contact and treatment uptake following hepatitis C virus screening and counseling among rural Appalachian people who use drugs. Int J Drug Policy. 2017;47:86-94. doi:10.1016/j.drugpo.2017.05.045
8. Pham TT, Keast SL, Farmer KC, et al. Sustained virologic response and costs associated with direct acting antivirals for chronic hepatitis C infection in Oklahoma MedicaidJ Manag Care Spec Pharm. 2018;24(7):664-676. doi:10.18553/jmcp.2018.24.7.664
9. Zibbell JE, Asher AK, Patel RC, et al. Increases in acute hepatis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014Am J Public Health. 2018;108(2):175-181. doi:10.2105/AJPH.2017.304132
10. World Health Organization. Hepatitis C fact sheet. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c. Updated July 27, 2020. Accessed August 29, 2020.
11. Fraser H, Vellozzi C, Hoerger TJ, et al. Scaling up hepatitis C prevention and treatment interventions for achieving elimination in the United States: a rural and urban comparison. Am J Epidemiol. 2019;188(8):1539-1551. doi:10.1093/aje/kwz097
12. National Academies of Sciences, Engineering, and Medicine. Eliminating the Public Health Problem of Hepatitis B and C in the United States: Phase One Report (2016). Washington, DC: The National Academies Press. doi:10.17226/23407. Accessed September 3, 2020.
13. National Academies of Sciences, Engineering, and Medicine. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report (2017). Washington, DC: The National Academies Press. doi:10.17226/24731. Accessed September 3, 2020.
14. Institute for Health Promotion Research, The University of Texas Health Science Center at San Antonio. South Texas Health Status Review. https://ihpr.uthscsa.edu/research-publications/other-reports/south-texas-health-status-review/
15. Texas Department of State Health Services. Health Facts Profiles, Texas, 2013. http://healthdata.dshs.texas.gov/HealthFactsProfiles. Accessed September 3, 2020.
16. Tenner L, Melhado TV, Bobadilla R, Turner BJ, Morgan R. The cost of cure: barriers to access for hepatitis C virus treatment in south Texas. J Oncol Pract. 2019;15(2):61-63. doi:10.1200/JOP.18.00525
17. Moreno GA, Wang A, Sánchez González Y, et al. Value of comprehensive HCV treatment among vulnerable, high-risk populations. Value Health. 2017;20(6):736-744. doi:10.1016/j.jval.2017.01.015

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Updated August 2021