Infection with Hepatitis C virus (or HCV) remains a significant public health challenge, with approximately 2.8% of the world’s population and around 3.5 million Americans affected. The disease is a leading cause of cirrhosis, liver transplantation, and liver-related deaths worldwide. Fortunately, modern direct-acting antiviral medications can cure over 90% of patients, with treatment success associated with significant reductions in liver cancer incidence, liver-related mortality, and improved quality of life. The World Health Organisation has sought to eliminate HCV by 2030, a goal that the US is not on track to achieve.

The U.S. Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force previously recommended one-time HCV screening for all adults born between 1945 and 1965 (the “baby boomer” generation) who have a five times greater likelihood of infection compared with the general population. Despite this and the availability of highly effective treatments, a significant gap remains in the hepatitis C care pathway. Many infected individuals, particularly those from racial/ethnic minorities and socioeconomically disadvantaged backgrounds, remain undiagnosed and untreated.

Prof. Mamta Jain of the UT Southwestern Medical Center and a team of researchers have conducted a series of studies exploring different interventions to improve HCV screening, diagnosis, and treatment rates, particularly in safety-net healthcare settings serving vulnerable populations.

In one study, the researchers evaluated a multifaceted intervention aimed at reducing health disparities in hepatitis C screening. Dr. Mamta Jain and her colleagues implemented and assessed a three-pronged approach: provider and patient education, an electronic medical record best practice alert, and increased HCV treatment clinic capacity.

The best practice alert intervention created an electronic reminder that would automatically trigger when a baby boomer visited any primary care clinic without a record of previous HCV testing. The alert provided a direct link to the HCV screening guidelines and was triggered at each outpatient clinic appointment until a completed lab result was in the system. On the education front, waiting room flyers informed patients about the screening recommendations. Finally, the researchers also expanded HCV clinic capacity from one clinic per week to four per week and added advanced practice providers to reduce wait times for patients diagnosed with chronic HCV infection.

In 2016, the HCV clinic further expanded by adding a nurse navigator, pharmacist, and pharmacy technician. These staff provided treatment and side effect education, assistance with insurance or patient assistance program forms, appointment reminders, and rescheduling of missed appointments until patients achieved a sustained virologic response, meaning that the virus was undetectable 12 weeks after completing treatment, which is considered a cure.

The researchers found that in the two years prior to the intervention, only 10.1% of 48,755 eligible baby boomers were screened for HCV. In the two years after implementing the multifaceted intervention, screening rates more than tripled to 34.6% among 34,093 eligible patients.

Prior to the intervention, HCV screening was lower among older baby boomers (born 1945-1955) and providers with large patient panels, while it was higher among high-risk subgroups including those with signs of liver disease, HIV-positive patients, and homeless patients. Post-intervention, the researchers observed increased screening uptake in previously underscreened groups, including older baby boomers, providers with larger patient panels, and patients with more than one prior primary care appointment. This demonstrated that the research team’s multifaceted intervention significantly increased HCV screening, particularly among hard-to-reach groups in a safety-net hospital system.

To further explore effective linkage to care intervention strategies, Dr. Jain’s colleagues conducted a clinical trial comparing two approaches to increase HCV screening. The first approach was exposing patients to ‘inreach’ interventions only, meaning the interventions that occur within the healthcare system during patient visits, specifically the alert that reminds providers to order HCV screening for eligible patients. The second was ‘mailed outreach’, in which clinicians proactively contacted patients outside of clinic visits through mailed letters inviting them to complete HCV screening.

In this study, over 12,000 baby boomers who had no previous HCV screening were randomly assigned to either receive usual care with inreach alone or inreach plus a mailed invitation for HCV screening. The mailed outreach intervention included a one-page, low-literacy letter in both English and Spanish describing the risk of HCV infection, the benefits and risks of screening, and a phone number to schedule the test.

The results showed that the combination of inreach and mailed outreach significantly increased HCV screening completion compared with inreach alone at 3 months. Among those who completed screening and had a positive HCV antibody result, a higher proportion of the patients in the ‘outreach group’ completed HCV RNA testing within 3 months. However, even with the combined approach, overall screening completion remained below 20%, highlighting the challenges of engaging this difficult-to-reach population.

Building on this foundation, Dr. Jain and colleagues conducted another study focusing on patient navigation to further improve linkage to care and treatment initiation. In this pre-post analysis, they compared outcomes between patients diagnosed with HCV before and after implementing a dedicated patient navigation program.

The patient navigation intervention targeted patients who had not been seen in the HCV Treatment Clinic within three months of a positive HCV RNA test. Research assistants made three phone calls to these patients, and if unable to reach them, sent a letter. Using predefined scripts, they discussed the HCV RNA result, the availability and benefits of treatment, and offered to schedule an appointment for treatment evaluation

Among the 1,353 patients studied, those in the patient navigation group had significantly higher odds of completing a treatment evaluation within 6 months and the time to evaluation in the clinic was significantly shorter. They were also much more likely to be linked to care within 6 months and begin treatment within 6 months compared with the usual care group. These benefits persisted at the 12-month mark. Importantly, once patients were linked to care, there was no significant difference in sustained virologic response rates between the groups, suggesting that the main barrier was getting patients into care, not the effectiveness of treatment itself.

Collectively, these findings have important implications for health systems aiming to improve hepatitis C screening and treatment rates, particularly among underserved populations. They suggest that while electronic alerts are an important foundation, they must be fortified with multiple approaches. Coupled with sufficient clinical capacity and personnel to effectively move patients through the entire care pathway from screening to treatment results in better outcomes for patients. Patient navigation services are essential to help guide patients through the complex care pathway and patient education through multiple channels including in-clinic materials and direct outreach helps to raise awareness and improve participation.

Another important finding across the studies was the differential impact of interventions among various patient subgroups. For instance, the multifaceted intervention was particularly effective at increasing screening among older baby boomers who had previously been underscreened. Similarly, the mailed outreach intervention showed a greater effect among Hispanic patients compared with other racial/ethnic groups. These findings underscore the importance of tailoring interventions to specific patient populations and suggest that a one-size-fits-all approach may not be optimal for achieving high screening rates across diverse patient groups. Health systems implementing similar programs should consider their specific patient demographics and potential barriers to care when designing interventions to maximize effectiveness and reach those at highest risk of undiagnosed HCV infection.

Dr. Jain and her colleagues’ work acknowledges the economic considerations involved in implementing these comprehensive HCV screening programs. However, the authors conducted cost analyses showing that the overall cost remains reasonable when considered per diagnosed case of HCV infection. For example, in the randomized trial comparing inreach with and without mailed outreach, researchers found that the entire outreach program resulted in a total cost of approximately $122,520, translating to costs of about $260 per additional completed HCV screening and $8,168 per additional confirmed HCV infection. These costs would likely still fall below traditional cost-effectiveness thresholds, particularly when considering the high costs of untreated HCV infection, which can lead to complications from cirrhosis, liver cancer, and the need for liver transplantation.

Dr. Jain and her colleagues suggest that future research should explore why HCV screening completion was low among the baby boomer cohort and underprivileged populations. Future interventions may need to be even more intensive, to reach the most difficult-to-engage patients, as overall screening completion remained below desired targets even with combined approaches.

Nevertheless, these studies provide a roadmap for health systems seeking to address Hepatitis C in vulnerable populations. Practitioners could consider their specific patient demographics and potential barriers to care and design similar interventions to maximize effectiveness and reach those at highest risk of undiagnosed HCV infection in order to reach HCV elimination targets in the future.