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The Centers for Disease Control and Prevention (CDC) estimates that 2.5 million individuals in the United States are living with chronic hepatitis C (HCV).1 The true prevalence may be as high as 4.6 million individuals infected with HCV, of whom at least 3.5 million are currently infected. The demographic of new HCV cases is changing from the baby boomer population born between 1945 and 1965, who account for 36% of new infections, to 23.1% of individuals born between 1966 and 1980 and 36.5% among millennials born between 1981 and 1996. This rise in infections among a younger demographic is driven primarily by the opioid epidemic and injection drug use (IDU).3 The CDC surveillance data from 2018 illustrate IDU among 72% of individuals with acute HCV infections.
Direct-acting antiviral agents (DAAs) have changed the course of chronic HCV, offering a cure to reduce the substantial burden of HCV. However, to treat, awareness of infection is necessary. As many as 50% of people infected with HCV may be unaware of their status, underscoring the need for broad screening. In 2020, the CDC and United States Preventive Services Task Force (USPSTF) issued new recommendations for universal screening of all adults over age 18, except in settings where the prevalence of HCV infection (HCV RNA positivity) is less than 0.1%.[6,7] The CDC recommends screening women with each pregnancy, although the USPSTF recommends one-time screening.[6,7] Opportunities for screening for HCV and linking individuals to care must be seized to reach all at-risk populations.
There are multiple roadblocks to diagnosis and treatment. The HCV treatment cascade of care, established by Yehia and colleagues, is a framework for evaluating the delivery of HCV care over time and within subgroups. The HCV treatment cascade reflects the steps along the health care continuum of gaps in care, in which people fall out care, and opportunities for improving interventions and engagement of HCV-infected persons by measuring the percentages associated with:
o Chronic HCV infection
o Confirmed HCV RNA positivity
o Linkage to outpatient care
o Initiation of HCV treatment
o Completion of HCV treatment
o Achievement of the ultimate goal of sustained virologic response (SVR) and cure.
In 2019, Calner and colleagues examined rates of diagnosis and linkage to care among five clinical locations and 28,435 patients screened within the Boston Medical Center (BMC) system between 2016 and 2019. BMC is an urban, safety net medical center. More than 70% of patients identify as a minority, more than 50% as African American, and more than 20% as Hispanic/Latino. Approximately 25% of patients are homeless and more than 30% of the BMC patient population do not speak English. The departments included in the study were the emergency department (ED), general internal medicine (GIM), inpatient, centers for infection disease (CIM) and family medicine (FM). The ED proved to be an excellent testing site for identifying new HCV-infected patients with high RNA positivity of 7.2%; however, there were many barriers with linkage to care, resulting in an identified need for strategies for stronger follow-through. GIM, inpatient, CID, and FM demonstrated stronger results linking patients to care and initiating DAA treatment. At the time of publication, the program continued with added strategies to address the barriers in order to improve linkage and treatment rates across all sites, especially in the ED and inpatient settings.
Like so many things in our lives, major changes and alterations to health care delivery have occurred since the spring of 2020 due to the COVID-19 pandemic. As COVID-19 hospitalizations mounted, resources needed to be preserved, shifting concerns about exposure and transmission of the virus, which limited access to onsite services. Health care shifted to telehealth with mostly good success, but unintended consequences surfaced. Emergency preparedness workflows were implemented in the ED to reduce volume and preserve personal protective equipment and staffing challenges. The impact of the pandemic on patients with HCV was evaluated by a BMC team comprised of Heather Sperring, MS, a data quality specialist at the Center for Infectious Diseases and Public Health Programs; Glorimar Ruiz-Mercado, MD, at the Center for HIV/AIDS Care and Research; and Ellisa M. Schechter-Perkins, MD, MPH, an ED physician. They analyzed prospective data from December 1, 2019 to June 30, 2020 and reported changes in screening, treatment, and medical care for patients with HCV. Their findings were published in the article. “Impact of the 2020 COVID-19 Pandemic on Ambulatory Hepatitis C Testing” in the Journal of Primary Care & Community Health.”
Hospital-wide data were collected and aggregated daily for all patients age 18 and older, including HCV antibody (Ab) tests and results, confirmatory HCV RNA tests and results, and HCV Ab–positive results. For comparison, researchers established December 1, 2019 to March 15, 2020 as the “before” period and March 16, 2020 to June 30, 2020 as the “after” period.
Given the systematic response to COVID-19 across all of health care, it is not surprising that researchers found a statistically significant decrease in HCV testing.
Hospital-wide, total HCV Ab tests decreased by 49.6% and new HCV-positive patient identification decreased by 42.1%.
Ambulatory clinic testing decreased by 71.9%, and new patients identified as HCV positive decreased by 63.3%.
Hospital-wide testing decreased 50.1% reflected in a reduction of 22.9 tests per day (95% confidence interval [CI]: 17.9-28.0, p < .001), and ambulatory-only department testing decreased 72.3% with 22.1 fewer tests per day (95% CI: 17.5-26.7, p < .001).
Balancing the need to put safeguards in place against transmission of SARs-Cov-2 in the hospital and ambulatory settings with long-term consequences of morbidity and mortality for undiagnosed and untreated HCV is a microcosm of the decisions and trade-offs health care providers have had to face throughout the pandemic. Telehealth can meet the needs of many patients with chronic disease, but people who inject drugs (PWIDs) may not have access to these services because of homelessness or lack of access to the internet. Streamlining visits, when possible, for rapid in-and-out lab visits can supplement virtual appointments. Authors concluded that continued monitoring of HCV screening trends is essential to minimize the long-term impact of the gaps in primary and preventive health care, which could be detrimental to HCV elimination. Adapting screening, treatment, and monitoring strategies to optimize telehealth will continue to leverage this valuable resource.
Why is this important?
IDU is the most important risk factor for HCV infection globally. In the United States, 64% of PWIDs are chronically infected and 80% of new HCV infections are related to IDU. The resilience of HCV on the syringe contributes to risk among young PWIDs who are more likely to share needles, cookers, and cotton filters, adding to the risk of acquisition shortly after they begin injecting.[12-14] When infectious diseases are comorbid with substance use disorder (SUD), they are associated with increased morbidity and mortality. Patients with SUD often have other medical and psychiatric comorbidities, have infectious and sexually transmitted diseases, and experience poverty and homelessness, putting them at great risk for poor outcomes. In addition to risk associated with IDU, COVID-19 mitigation strategies such as social distancing and stay-at-home orders have resulted in the closing of SUD clinics and treatment centers, interrupting SUD treatment services. This in turn has interrupted the ability of PWID to seek HCV screening, seek and receive confirmatory testing, and schedule treatment.[16,17]
Underdiagnosis is the largest gap in the cascade of care. Keeping PWID within the HCV treatment cascade, from diagnosis to treatment to SVR, is a priority because of the high burden of infection and the potential to transmit HCV to others. Several studies have demonstrated that IDU risk behaviors remain stable or decrease during or following DAA therapy. Modeling of treatment in PWID highlights the need for prevention strategies including safe syringe programs, harm reduction, medication for opioid use disorders (MOUD) therapy concurrent with HCV treatment, and education and counselling regarding HCV transmission and use.[18,19] Multiple trials have demonstrated successful achievement of SVR in PWID. The SIMPLIFY trial followed 103 persons with IDU (74% in the past month, 36% daily in the last month) who were treated with sofosbuvir and velpatasvir for 12 weeks. Of the patients, 94% achieved HCV cure with no virologic failures and 96% demonstrated 90% adherence. Drug use before and after did not affect SVR.
The goal of the World Health Organization (WHO) is to reduce HCV infection incidence by 80% and reduce HCV-associated deaths by 65% by 2030, which will require improved access to testing and treatment, as well as harm reduction, mental health support, and substance use support. The COVID-19 pandemic will continue to pose challenges that will require outside-the-box approaches to ensure that access to health care and testing will bring additional at-risk individuals into the system for diagnosis and treatment of their HCV with the ultimate goal of a cure.
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1. Centers for Disease Control and Prevention [CDC]. Hepatitis C questions and answers for health professionals. CDC Website. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#a3. Last reviewed August 7, 2020. Accessed March 28, 2021.
2. Edlin BR, Eckhardt B, She M, et al. Toward a more accurate estimate of the prevalence of hepatitis C in the United Stated. Hepatology. 2015;62(5):1353-1363.
3. Ryerson AB, Schillie S, Barker LK, et al. Vital signs: newly reported acute and chronic hepatitis C cases—United States, 2009-2018. MMWR Morb Mortal Wkly Rep. 2020;69(14):399-404.
4. Centers for Disease Control and Prevention [CDC]. Viral hepatitis surveillance report 2018—hepatitis C. CDC Website. https://www.cdc.gov/hepatitis/statistics/2018surveillance/HepC.htm#Table3.1. Last reviewed August 28, 2020. Accessed March 28, 2021.
5. Kin H-S, Yang JD, ElSerag HB, Kanwal F. Awareness of chronic viral hepatitis in the United States: an updated from the National Health and Nutritional Examination Survey. J Viral Hepat. 2019;26:596-602.
6. Schillie S, Westerd C, Osborne M, et al. CDC recommendations for hepatitis C screening among adults—United States, 2020. MMWR Recomm Rep. 2020;69(2):1-17.
7. U.S. Preventive Services Task Force [USPSTF]. Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA. 2020;3(3):e200538.
8. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V. 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.
9. Calner P, Sperring H, Ruiz-Mercado G, et al. HCV screening, linkage to care, and treatment patterns at different sites across one academic medical center. PLoS ONE; 2019;14(7):e0218388.
10. Sperring H, Ruiz-Mercado G, Schecter-Perkins EM. Impact of the 2020 COVID-19 pandemic on ambulatory hepatitis C testing. 2020. J Prim Care Community Health. 2020;11:215013272096554.
11. U.S. Department of Health and Human Services [HHS]. Hepatitis C virus infection in young persons who inject drugs: consultation report. Hep Free NYC Website. https://hepfree.nyc/wp-content/uploads/2017/08/hcv-and-young-pwid-consultation-report.pdf. Published February 26, 2013. Accessed March 28, 2021.
12. Paintsil E, He H, Peters C, et al. Survival of hepatitis C virus in syringes: implication for transmission among injection drug users. J Infect Dis. 2010;202:984-990.
13. Doerrbecker J, Friesland M, Ciesek S, et al. Inactivation and survival of hepatitis C virus on inanimate surfaces. J Infect Dis. 2011;204:1830-1838.
14. Doerrbecker J, Behrendt P, Mateu-Gelabert P, et al. Transmission of hepatitis C virus among people who inject drugs: viral stability and association with drug preparation equipment. J Infect Dis. 2013;207:281-287.
15. Kolla BP, Oesterle T, Gold MS, et al. Infectious diseases occurring in the context of substance use disorders: a concise review. J Neurol Sci. 2020;411:116718.
16. Wingrove C, Ferrier L, James C, Wang S. The impact of COVID-19 on hepatitis elimination. Lancet Gastroenterol Hepatol. 2020;5(9):792-794.
17. Walters SM, Seal DW, Stopka TJ, et al. COVID-19 and people who use drug: a commentary. Health Behav Policy Rev. 2020;7(5):489-497.
18. Terrault NA. Hepatitis C elimination: challenges with under-diagnosis and under-treatment. F1000Res. 2019;8:F1000 Faculty Rev-54.
19. Hajarizadeh B, Cunningham EB, Valerio H, et al. Hepatitis C reinfection after successful treatment among people who inject drugs: a meta-analysis. J Hepatol. 2020;72(4):643-657.
20. Grebely J, Dalgard O, Conway B, et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3(3):153-161.
21. World Health Organization [WHO]. Global Health Sector Strategy on Viral Hepatitis 2016-2021. WHO Website. https://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/. Published June 2016. Accessed March 28, 2021.
22. Binka M, Janjua N, Grebely J, et al. Assessment of treatment strategies to achieve hepatitis C elimination in Canada using a validated model. JAMA Network Open. 2020;3(5):e204192.
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.