Despite the availability and high efficacy of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment, numerous gaps in care remain because of a range of factors. Many individuals with HCV are asymptomatic and unaware that they are infected, according to a 2019 study published online in Clinical Gastroenterology and Hepatology.1 The authors found that 49% of adults with HCV infection were aware of their infection status, of whom 45% received treatment, and 59% of these patients achieved a sustained virologic response.

In addition, certain populations with a high risk for HCV infection, such as people who inject drugs, typically have low engagement with healthcare services, and thus may not receive screening or complete treatment, and individuals who have been diagnosed may not be able to afford the extremely high cost of DAAs.2

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For an in-depth discussion regarding these issues and potential solutions to address gaps in HCV treatment, Hepatitis Advisor interviewed M. Cabell Jonas, PhD, senior research program consultant and operations research associate investigator at Mid-Atlantic Permanente Medical Group in Rockville, Maryland; Norah Terrault, MD, MPH, chief of the Division of Gastrointestinal and Liver Diseases and professor of medicine at the Keck School of Medicine of the University of Southern California, Los Angeles; and Kali Zhou, MD, transplant hepatology fellow at the University of California, San Francisco. Dr Jonas is one of the authors of a 2018 paper published in Infectious Disease Clinics of North America that describes a comprehensive program designed to close multiple gaps in care.2 Dr Terrault and Dr Zhou coauthored the 2019 study reported in Clinical Gastroenterology and Hepatology.1

Hepatitis Advisor: What are some of the main gaps in HCV care and potential reasons for these?

Dr Jonas: First, when we are considering gaps in HCV care, we need to start by recognizing the gaps that occur before a diagnosis. One major gap is in identifying patients at risk and screening these patients for HCV. It is estimated that roughly one-half of those infected with HCV don’t even know they have the disease.1,2 HCV impacts the large baby boomer population – which is 5 times more likely to have HCV – but the disease is also increasing along with the opioid epidemic in the United States.2 Since many of the patients with HCV may be asymptomatic, proactive HCV screening is essential. It’s critical that physicians are supported with tools to easily identify at-risk patients for HCV screening.

Second, gaps in the HCV laboratory testing cascade persist, even though this challenge is well-documented in the literature. Many patients obtain HCV antibody testing but never return for those results, or if the patient is HCV antibody positive, many patients don’t return for the needed confirmatory HCV RNA testing, resulting in an incomplete diagnosis. When laboratory testing cascades require multiple trips to the lab for the patient, it increases the likelihood that patients will fall through the cracks.

Third, treatment with curative medications, though significantly improved over prior treatments for HCV, still requires weeks of medication compliance to achieve sustained virologic response. Patients can experience financial barriers when accessing these very costly medications, and may need general medication adherence support. Patients may need financial support and clinical support to effectively complete the medication course.

Additional gaps within each category exist, but focusing on those listed here can advance progress in terms of improving HCV screening and care.2

Dr Zhou: Despite increasing uptake of DAAs and cure for many patients with HCV across the United States, there is still much work to be done to address drop-offs along the HCV care continuum. In our paper, we highlight the key gap within the very first step, which is awareness.1 While awareness and screening are closely related, awareness relates to the patient experience, and there may be many HCV-infected patients who have been screened by providers, yet remain unaware of their infection. The impetus to progress through the care continuum requires patient buy-in and engagement, thus, awareness is a crucial, yet less considered, component of HCV care.

There are many potential reasons for persistent low awareness among individuals who are infected with HCV. Certainly, the major concern is that they are not being screened. Our study demonstrates that those who are unaware are more likely to be outside of traditional recognizable risk groups, such as Hispanics or those without a history of injection drug use.1 This suggests that we have done a great job of targeting high-risk groups for screening. The US Centers for Disease Control and Prevention (CDC) recommendations to screen anyone born between 1945 and 1965 has counteracted this somewhat, such that the age group with greatest awareness (60%) was the baby boomers.3,1

The other reason might be that some of those who are unaware of infection are so-called “hard-to-reach” populations, such as prisoners, homeless people, and active injection users. The former 2 populations are not captured within NHANES; thus, we believe that the true proportion of unaware people is in reality much higher. Of course, awareness is only one piece. We saw further care continuum drop-offs among those who are aware because only 45% of those reported treatment.1 While current DAAs have removed many of the barriers that existed with interferon-based therapies, there is still much to address related to linkage to specialty care and treatment access, particularly with respect to insurance coverage and cost across different states and healthcare systems.

Hepatitis Advisor: What are some ways in which these gaps can be addressed?

Dr Jonas: In Kaiser Permanente Mid-Atlantic States, we closed all these gaps through our Hepatitis C Cascade of Care program.4 This physician-led, care coordinator-supported, and research-based program uses patient-centered workflows, technology, and testing innovation to improve HCV screening and care for our patient population.

We closed the gap in at-risk patient identification by using electronic medical record-based alerts that prominently indicate when patients are eligible for HCV screening. These alerts make it easy for physicians and staff to identify when a patient needs screening, and initiate the screening cascade. These alerts fire in all departments. Therefore, when patients come in for any visit, including all primary and specialty care, there is an opportunity to screen for HCV. As a result of this innovation, we have screened over 72% of our baby boomer-aged population for HCV.

Our program also closes gaps in the testing cascade through an innovative, automated laboratory testing process. Now, a patient can be tested for HCV antibody, HCV RNA, hepatitis B surface antigen, and HIV, using blood from just 1 visit to the lab. This saves patients time and eliminates the loss of follow-up that occurs when multiple laboratory visits are needed. With 1 trip, our patients have a complete diagnosis and can move on to the next steps in care. A dedicated HCV care coordinator ensures that all testing is completed and provides patients with the information needed about their diagnosis and next steps. These automated processes mean that patients tested through the program are more likely to receive the necessary testing and to have a gastroenterology visit.

In terms of access to treatment, we offer financial assistance programs and a pharmacist-supported program to support medication adherence.

Dr Zhou: Expanding screening campaigns beyond traditional risk groups is 1 way to address these gaps. For example, we identified racial disparities in awareness, with Hispanics found to be the least aware of their HCV infection.1 Partnering with community-based organizations to educate and provide testing within cities or areas with large Hispanic populations may be a high-impact strategy.

We also found that the majority of those with abnormal liver tests were unaware. Increasing provider education on what constitutes an abnormal alanine aminotransferase level in clinical practice (>25 in women, >35 in men, notably lower than the cut-offs provided by laboratories) may lead to increased screening among those without clear HCV risk factors. For marginalized or “hard-to-reach”  groups, colocating HCV screening and treatment in places where they may already be engaged in care, such as needle exchanges or opiate substitution programs, is likely more high-impact.

Increasing uptake of HCV screening, education, and even access to treatment for prisoners during their period of incarceration would prevent downstream effects of HCV infection, but also potentially decrease transmission once released. Lastly, the growth of programs, such as Project ECHO has really expanded access to specialty care among underserved and rural communities and empowered primary care physicians to administer HCV treatment. (Read about this program here: “Telementoring to Support Community Providers in HCV Treatment“) Eliminating the need for an additional “linkage” step in the continuum would be highly valuable in scaling up HCV treatment on a national level.

Hepatitis Advisor: What are the relevant treatment implications or other recommendations for clinicians?

Dr Jonas: It is important to note that the redesign of our Hepatitis C Cascade of Care program was physician led. Physicians and other clinicians can help identify the specific gaps in care and be partners in developing technology and laboratory-based solutions to those problems. Redesigning a program can appear challenging, but there are easy places to start.

First, physician and clinical staff education about hepatitis C is critical. Establishing an awareness of the problems and challenges paves the way for innovations and solutions.

Second, all clinicians should implement a medical record-based alert for at-risk patients to be screened for HCV, starting with the baby boomer-aged patients and then expanding to other at-risk groups, such as those who are using intravenous drugs. Alerts have shown effectiveness across various care sites, care models, and electronic medical record systems.

Third, minimize the burden of testing for patients. Those at risk for and diagnosed with HCV are often vulnerable patients. Reducing trips to the laboratory and offering care coordinator support can enable these patients to complete the testing process and remain engaged. As an initial step, implement a laboratory testing process that, at minimum, includes automated reflex testing for HCV antibody to HCV RNA. It is critical that patients obtain an HCV diagnosis with 1 visit to the lab. Consider whether a care coordinator could support patients in completing the steps to diagnosis and treatment. In our program, the coordinators and pharmacy staff engage patients via telephone or video visits, making it easier for patients to remain in contact and engaged in care without visiting a clinic.

Dr Terrault: Despite the spotlight on elimination of viral hepatitis by the World Health Organization and CDC, there remain major gaps in achieving this in the United States, and all clinicians play a key role in getting the country closer to achieving this goal. First and foremost, every clinician should ask him or herself what they are doing to identify those infected and whether their practices could be improved. Diagnosis is the critical first step in getting patients with HBV and HCV the care they need. [In addition to their findings regarding HCV awareness, Dr Zhou and Dr Terrault also found that only 32% of adults with HBV infection were aware of their infection status, and 28% of these individuals reported treatment.1]

Second, there should be enhanced partnerships between primary care and specialists to ensure that the continuum of care from diagnosis to treatment is attained.

Hepatitis Advisor: What are remaining needs in this area in terms of research, patient education, or otherwise?

Dr Jonas: Looking to the future, it will be important to continue to take a patient-centered approach to solving complex infectious disease challenges. There are major opportunities to continue to make infectious disease screening and care accessible for patients by using technology, remote interactions, such as telephone and video visits, and streamlined processes that are supported by research demonstrating their effectiveness. Also, it’s better to prevent disease than to have to treat it, so it’s important to continue to educate patients about disease prevention.

We will continue to advance infectious disease care by conducting research on work underway, as well as continuing to translate new research into clinical care delivery. Developing and deploying interdisciplinary teams that can translate evidence-based processes into clinical care will be imperative.

Dr Terrault: Our study highlights the many opportunities to improve the cascade of care for persons living with HBV or HCV. A multifaceted approach is needed, but I would highlight the need for patient education and engagement. Many patient advocacy groups are working to raise public awareness, highlighting the serious consequences of undiagnosed chronic HBV and HCV infection, particularly liver cancer, and promoting screening, treatment, and prevention. These efforts are incredibly important and should be enhanced as a key element of the elimination strategy.

References

1. Zhou K, Terrault NA. Gaps in viral hepatitis awareness in the United States in a population-based study [Published online June 4, 2019]. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2019.05.047

2. Jonas MC, Loftus B, Horberg MA. The road to hepatitis C virus cure. Infect Dis Clin N Am. 2018;32(2):481-493.

3. Centers for Disease Control and Prevention. Testing recommendations for hepatitis C virus infection. https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm. https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm. Accessed July 1, 2019.

4. Jonas MC, Rodriguez CV, Redd J, et al. Streamlining screening to treatment: the Hepatitis C cascade of care at Kaiser Permanente Mid-Atlantic States. Clin Infect Dis. 2016;62(10):1290-1296.