Providers’ Perspectives of Hepatitis Delta Virus Screening and Recommendations for Improvement: A Qualitative Investigation

Abstract

Background and Aims

The prevalence of hepatitis delta virus (HDV), which causes more severe liver disease than infection with hepatitis B virus alone, has risen in the United States and globally. However, the true burden of HDV is poorly understood due to low screening rates. Both patient- and provider-level factors may contribute to low HDV screening; however, our understanding of such factors is limited. The purpose of our study was to gain a comprehensive understanding of the perceived barriers and facilitators to HDV screening and treatment from the perspective of healthcare providers

Methods

We recruited participants who were members of the American College of Gastroenterology, the American Association for the Study of Liver Diseases, and/or the Gastroenterology and Hepatology Advanced Practice Providers organization. We conducted in-depth, qualitative interviews with 46 racially diverse providers practicing in practice environments throughout North America.

Results

The interviews revealed six themes related to barriers to screening, including (1) limited knowledge and awareness, (2) lack of clear guidelines, (3) operational challenges, (4) cost and insurance, (5) provider-related factors, and (6) patient-related factors. Recommendations for increasing screening included (1) provider education and awareness, (2) advocacy for universal screening, (3) improved guidelines, (4) streamlined testing process, (5) increased access to screening tests, (6) public awareness campaigns, (7) more research on HDV, (8) financial assistance, and (9) accountability measures.

Conclusion

Identification of gaps in knowledge and barriers to HDV screening are critical toward implementation of successful screening programs, essential for accurately estimating HDV prevalence and connecting patients with HDV infection to appropriate, individualized care.

Introduction

Hepatitis delta virus (HDV), a single-stranded RNA virus, causes liver disease only in the presence of hepatitis B virus (HBV) as the HDV virion relies on hepatitis B surface antigen (HBsAg) to enter hepatocytes and for assembly.^1,2 Despite a global decline in HBV rates, HDV persists, with estimates suggesting between 12 and 20 million people are infected worldwide.^3,4 Globally, anti-HDV prevalence has been estimated at 0.16% of the general population.³ Among individuals who are HBsAg-positive, the overall estimated prevalence is 4.5%, with significantly higher rates observed in individuals who inject drugs, hemodialysis recipients, men who have sex with men, commercial sex workers, and individuals with hepatitis C virus or HIV.³ While HDV infection can occur simultaneously with acute HBV infection,² most chronic HDV infections result from acute HDV infection in individuals with chronic HBV. Compared to individuals with HBV alone, coinfection with HBV and HDV is associated with a significantly increased relative risk of cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation, transplantation, and mortality.⁵ Additionally, acute HDV superinfection can cause fulminant liver failure.³

Recognizing the severe clinical impact of HDV, several international organizations have issued screening recommendations. The European Association for the Study of the Liver (EASL)⁶ Clinical Practice Guidelines strongly recommend that all HBsAg-positive individuals be screened at least once for anti-HDV antibodies, with retesting in certain clinical scenarios such as aminotransferase flares or decompensated liver disease. Confirmation of active infection requires HDV RNA testing using a standardized assay. The EASL guidelines further recommend that all patients with chronic HDV infection undergo regular monitoring every 6–12 months, be considered for antiviral therapy, and receive HCC surveillance if they have advanced fibrosis or cirrhosis. Similarly, the Asian Pacific Association for the Study of the Liver⁷ recommends systematically screening for HDV in all HBsAg-positive patients. In contrast, current guidance from the American Association for the Study of Liver Diseases (AASLD)⁸ recommends HDV screening based on the presence of risk factors and/or clinical indications.

Despite the widespread understanding that HDV infection substantially worsens the severity of liver disease, our understanding of HDV’s true prevalence is limited by low HDV screening rates.^3,4 Estimated HDV screening rates are low and vary widely, with estimates reported at 2.6% in a state-based analysis of over 8000 individuals with HBV,⁹ 6.7% in a large national sample of 157,333 patients with HBV,¹⁰ 12.9% in a single-center study of 11,190 patients,¹¹ and 19.7% in 12,002 patients treated through the Veterans Health Administration.¹⁰

Low HDV screening rates may reflect uncertainty regarding screening eligibility and limited knowledge regarding available treatments.¹² Additionally, there was wide variability in perceived epidemiologic burden among survey respondents (data unpublished) and significant gaps in knowledge about the use of appropriate HDV screening tests.¹³ In addition to lack of information about the impact of HDV infection,¹⁴ there are limited data about healthcare providers’ appreciation of the consequences of HDV/HBV coinfection. This study recruited providers from various regions of the country, specialties, educational backgrounds, and practice types to assess knowledge, identify perceived barriers and facilitators to HDV screening and treatment, and gather recommendations for improving screening.

Methods

Procedures

Participants were recruited from a larger sample of 300 healthcare providers who had participated in an Internet-based survey on HDV knowledge and screening barriers.¹² These participants were identified through email listservs from the American College of Gastroenterology, five special interest groups of the AASLD, and the Gastroenterology and Hepatology Advanced Practice Providers organization. The survey link was also circulated on social media, for example, Facebook and Twitter. Using purposive sampling methods,¹⁵ we included only active, licensed healthcare professionals providing direct patient care and holding one of the following degrees: (1) Doctor of Medicine, Doctor of Osteopathic Medicine, Bachelor of Medicine, Bachelor of Surgery, or equivalent degree; (2) Physician Assistant-Certified; (3) Advanced Registered Nurse Practitioner or equivalent degree. We excluded any nonlicensed providers and those unable or unwilling to provide informed consent. In the survey, we asked participants to indicate interest in participating in in-depth interviews by providing their emails. Of the 105 individuals who provided their emails, two declined to participate when contacted, forty-six did not respond to the introductory email to schedule the interview, ten initially responded but either did not report for their scheduled interview or did not schedule interviews, and one email was invalid. Forty-six participants who demonstrated an interest in participating in the study completed interviews.

Semistructured interviews were conducted with 46 providers from diverse practice settings across the US providers were recruited from gastroenterology, family medicine, internal medicine, infectious diseases, and hepatology. The semistructured interview protocol, developed by P.D.J. and D.L.L., is available in the supplementary materials. S.H. conducted all interviews via Zoom, which were audio and video recorded after confirming participant identity and obtaining verbal informed consent. Deidentified audio recordings were initially transcribed using Otter.ai and the transcription accuracy was verified by S.H. who edited transcripts as necessary. All participants received a $100 gift card as compensation. The study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist¹⁶ and was approved by the University of Miami Miller School of Medicine Institutional Review Board (IRB# 20211222).

Participants

Of the 46 participants, seven identified as African American/Black (15.2%), eighteen as Asian (39%), two as mixed race (4.3%), and nineteen as White (41%). Among these participants, one identified as Hispanic (2.2%). Of note, the Internet-based survey study included 12% Black, 27.7% Asian, 54% White, and 8.4% Hispanic participants; thus, our interview participants were more racially and ethnically diverse.¹² Twenty-five participants identified as female, and twenty-one as male. One participant identified as “middle-aged.” Of the others who specified their age, the age range was 26 to 71 (mean [M] = 42.73, standard deviation [SD] = 11.08). Participants resided in the Midwest (n = 6), Northeast (n = 14), South (n = 18), and West (n = 7) regions of the United States. One participant resided in Canada. Participants were medical doctors (n = 35), physician assistants (n = 6), and nurse practitioners (n = 5).

Excluding those who were currently completing fellowship, the number of years in practice ranged from 1.5 years to over 30 years (M = 12.17, SD = 8.83). Ten participants were completing their fellowship at the time of the interview (n = 10). Self-reported specialties included gastroenterology (n = 17), gastroenterology and hepatology (n = 8), hepatology (n = 15), liver transplantation (n = 1), and transplant hepatology (n = 4). Only one interviewee reported practicing internal medicine/hospital medicine. Practice settings included academic medical centers (n = 23), community hospitals (n = 4), private/group/hybrid practices (n = 4), outpatient clinics (n = 11), and Veterans Affairs medical centers (n = 4).

The number of HDV cases encountered by providers varied widely, ranging from 0 to 550 over their careers. Fourteen participants reported never having encountered an HDV patient, while seventeen had seen between one and five cases. Only six providers had encountered 20 or more HDV patients throughout their careers. Providers who reported greater exposure to HDV cases generally demonstrated broader knowledge across multiple domains, including HDV prevalence rates, modes of transmission, identification of populations most vulnerable to infection, clinical sequelae, prevention strategies, available diagnostic tests, and management considerations. However, some participants who reported routinely screened all HBV patients for HDV had never encountered a confirmed case.

Geographic differences were also observed, with providers in the Northeast reporting the highest levels of experience with HDV patients. Providers with over 20 years of experience had encountered the highest average number of HDV cases. However, many noted that screening practices have evolved over time, suggesting that their earlier experiences may not fully reflect current trends. In contrast, early-career providers (<5 years of experience) had encountered few, if any, HDV patients.

Qualitative Data Coding and Statistical Analysis

Interview transcriptions were independently coded and analyzed by two researchers (S.H. and D.L.L.) using line-by-line coding to identify themes and subthemes, ensuring the inclusion of all data.¹⁷ Researchers employed the constant comparison method throughout the coding process,^18,19 wherein each participant’s data were compared with all previous participants’ data, allowing researchers to ascertain themes across participants as well as themes unique to individual participants. If disagreements occurred within coding, researchers (S.H., D.L.L., P.D.J.) discussed to reach consensus. Directed content analysis was used to address the research questions, utilizing prior knowledge about HDV as the starting point.¹⁸ Commonly used in healthcare research, directed content analysis enhances the rigor and trustworthiness of the data analysis and results.²⁰ Descriptive statistics, that is, number and proportion for categorical variables and mean and SD for continuous variables were used to describe the sample of participants as above.

Trustworthiness

To further ensure trustworthiness, final themes and subthemes were shared with the entire team to assess the accuracy, comprehensiveness, and quality of the interpretation and findings. Furthermore, the team maintained an audit trail for the steps of theme development. Data collection stopped only after saturation was reached and three additional participants were interviewed to verify that no new themes emerged.

Results

The results section is organized into two a priori themes: “Barriers to HDV Screening and Treatment” and “Recommendations for Improving Screening,” with the themes and illustrative quotes detailed in Tables 1 and 2 and Figure 1, respectively. It is important to note that providers’ knowledge gaps did not differ significantly by specialty. However, years of practice appeared to influence breadth of knowledge. Providers with fifteen or more years of practice generally demonstrated broader knowledge of HDV, including its prevalence, clinical sequelae, prevention strategies, clinical implications, treatment options, and vulnerable populations. In contrast, those with fewer than 5 years of experience exhibited greater variability in knowledge—while some demonstrated familiarity with basic aspects of HDV transmission and disease progression, others reported minimal exposure or understanding of its clinical implications and management. Notably, nurse practitioners interviewed appeared to have more limited knowledge and less direct experience with HDV patients compared to physicians and physician assistants.

Table 1.

Barriers to Screening and Treatment and Illustrative Quotations

Theme 1: Limited knowledge and awareness
Limited knowledge and awareness	“My understanding is that patients…don't know about D, a lot of providers don't know about D, certainly primary care providers really aren't that familiar with D. So awareness is one definite problem.” “They probably do not know the risk factors. So even if they think they're doing risk factor based screening, they don't know the risk factors.”
Theme 2: Lack of clear guidelines
Lack of clear guidelines	“Not specifically knowing if one test is better than another, should it just be the antigen? Antibody? Does it need to be both? Or is it just the PCR?” “There needs to be… (information on) where to send the labs and what labs to send…and who to screen.”
Theme 3: Operational challenges
Subtheme 3.1: Testing procedures	“I think there [are] also issues with the type of testing available, because if it’s not readily available, then there's going to be reluctance on the physicians’ part to start testing.” “There's a 0% chance I would ever order a Hep D screening test as outpatient labs ever. There's no situation where I’d do that.”
Subtheme 3.2: Lab issues	“We have community practices, and there have definitely been places where I've ordered for D antibody. And I've gotten calls from the labs that ‘we don't know how to do this, we can't do this, this is a really expensive test, do you really want this?’ I’m like ‘I don't really think it's that expensive, and yes, I really would like it. And then it turns out that they just don't know how to get it.” “It used to be that you could order something, and especially if they didn't go to our lab, you'd get a call from the lab that…they didn't have that test, or (it) just wouldn't be drawn.”
Subtheme 3.3: Lack of time	“It’s just a matter of… adding an extra box, which still is time, you know, every minute counts throughout the day, so I think it would be more time.” “Because we miss this social history and, or the family history, I think we're usually like, in a hurry. And we don't, wouldn't ask those appropriate questions to the patient. Maybe that's one of the reasons.”
Theme 4: Cost and insurance
Cost and insurance	“…Get them in, and then the expense of screening them. And then if you're going to screen them, you're going to make a commitment, if they're positive, to treating them. So again, expenses there.” “But I do think that when you're looking at why people may not screen often is because your International Classification of Diseases (ICD) codes are, the things that you're using to justify the billing, may not work. And then rather than trying to find something that can allow that test to be paid for, you're just like, well just don't draw it then because I can't figure out how to get it paid for.”
Theme 5: Provider-related factors
Subtheme 5.1: Low perceived prevalence	“If we are screening 1 million to find one case that really needs to be treated, then is it worth it?” “I know, there's been a push lately… to kind of put hep D out there. But it really isn't something that's talked about often at any of our meetings or societies. And so, the prevalence and incidence seem to just be so low.”
Subtheme 5.2: Perceived futility of testing	“Again, if there was absolutely no effective therapy at all, I wouldn't want to be like… what's the point then? What are we doing? Why are we checking? We can't do anything about it. Just for interest’s sake, to know about it.” “I guess the third thing is, what are we going to do? You know, I mentioned before, we got, we got pegylated interferon, primarily Pegasys, that's the main one. And it has all these side effects. And before you can give this, which is an injection, as I said, weekly, to patients, you have to tell them what the possible problems are. And so when you talk about flu-like…symptoms, and depression, and blood effects, and you know, like anemia and other things, patients say, ‘Really, Doc? You're gonna make me feel sicker than I am now.’ So that kind of stuff is a big problem with, with interferon.”
Subtheme 5.3: Forgetting to screen	“Forgetting about it…I think that's the only thing that would happen. I just accidentally didn't do it.”
Theme 6: Patient-related factors
Subtheme 6.1: Patient compliance	“A not insignificant number of our patients are intravenous drug users or were intravenous drug users. And you have to be careful about compliance because they may say, “Yes, I'll give you the star, the stars and the moon,” but they may not follow through. So compliance is an issue.”
Subtheme 6.2: Impact of false positives	“False positives, I guess, are always a concern for when you're screening patients for something.” “Obviously, just like in any setting, people are often concerned about over-testing and populations with low prevalence, because you may have a false positive, for example, and that may cause unnecessary anxiety in patients who receive that type of test result.”

PCR, polymerase chain reaction.

Table 2.

Recommendations to Enhance Screening and Treatment

Theme 1: Education and awareness for providers

“(General practitioners in small communities) don't know about HDV. They've never heard of it. They don't keep up with continuing medical education.” “I've run into gastroenterologists who aren't that familiar with B. For example, they don't know that you have to have B in order to have D. So, education there is critical.” “(I want to know more about) basically everything, but specifically, methods or modes of transmission, kind of presentation, and treatment and monitoring would be kind of the big things.”

Theme 2: Universal screening

“…it's easier just to screen everybody than trying to give additional information about which patient population to screen. Because I think a lot of times people pigeonhole themselves and miss… individuals by just making assumptions.” “For me, (testing is) very important… I take care of a few of these patients, and I have seen their disease course and (severity)… it's important to know early (because)… the management of… delta is different. So you do need to screen in order to know what to do about their management.”

Theme 3: Improve screening guidelines and recommendations

“I think the most effective way would be dissemination of guidance and guidelines. Centers for Disease Control and Prevention (CDC) just came out with the recommendation for universal screening for hepatitis B. And… when (the message) carries over into things like social media… (it) can get to people very quickly.” “People are very slow to change, they need to hear the message over and over five to seven times, people call it the rule of sevens. So every clinician needs to hear the recommendation from the CDC and the Morbidity and Mortality Weekly Report (MMWR) that's coming out in the next few weeks to test all adults for B, then the CDC and AASLD…need to come up with a simple statement to check every B patient for delta… repeat as much as possible till everybody becomes compliant.”

Theme 4: Streamlined testing process

“I think similar to C, you need to kind of have… an alert… (in that) maintenance section of your EMR, there really should be something that says your patient’s not been screened for hepatitis B or not been vaccinated for hepatitis B.” “The other is EMR, I think is very powerful tool in terms of flags or like clinical reminders for screening. We found that to be impactful for hepatitis C… that could be very impactful for hepatitis B… and similarly, if we move toward screening all hep B patients for delta, I think that could be very useful also because… most clinicians want to do the right thing.”

Theme 5: Increase availability and accessibility of screening tests

“(Ordering HDV screenings) is infinitely easy if the lab offers it, it's infinitely difficult if the lab doesn't offer it.”

Theme 6: Public awareness campaigns

“Web-based platforms for patients in their native language or their preferred language is really helpful,…just simple, patient-centered language to explain…” “…I think you would want to educate the communities who may have higher prevalence.” “…it's such a rare thing… I don't really know that there's a huge benefit to educating the general public about hepatitis D… but to give information to patients with hepatitis B because that's actually the group of people that, for the most part, are at risk.”

Theme 7: More research on HDV

“We don't have many patients with it, and the response has been variable, the treatment is not good. What I'd like to know is if there are the better treatments for this disease, and that we can incorporate in our armamentarium.” “If there is any other measures of prevention and the current landscape of treatment and what's on the horizon. Or is there anything already approved, which I'm not aware about?” “So to me, it doesn't make any sense that if you look at the pegylated interferon treatment trials, if you treated hep delta with peg, you could have a relapse several years later. Now that could have been the testing was bad that you just didn't recognize that you had low level viremia that never cleared or maybe they really did relapse. But when you have a patient that you screen, and they're delta antibody positive, but RNA negative, you don't follow them anymore. You're like, ‘Yup, you were exposed, you don't have delta,’ which would imply a degree of curability, right? That if we, or if you’re Hep C antibody positive and you’re PCR negative, we say ‘yup, you spontaneously cleared, you don't have hep C, can't relapse.’ We use that same messaging around spontaneous clearance of delta. But we don't use that messaging around therapeutic, you know, quote, unquote, clearance or reduction of delta. And so I'd like to know where, where that line in the sand is, can we actually cure patients of their delta?”

Theme 8: Financial assistance for screening and treatment

“The population at risk, is probably the population that can least afford the diagnostic and treatment for this disease. So, you know, a grant or some kind of way of getting this under control.”

Theme 9: Accountability measures for HDV screening

“If you are given a report that you have…400 B patients… under your management, none of which have delta testing, you might be like, ‘Oh, maybe I should think about this a little harder.’ so I think there are ways that healthcare systems could, could report back on how well we're doing, almost like a QI project…” “And if they’re Hep B positive, it, there really should be something that says… ‘with or without delta,’ every single time…to push individuals to do something, even if they don't exactly understand why they're doing it.”

PCR, polymerase chain reaction.

Figure 1.

Provider recommendations to improve screening for hepatitis delta virus.

Barriers to HDV Screening and Treatment

Participants identified a wide range of perceived barriers to HDV screening and treatment at the individual, practice, and systemic levels. Six themes emerged from the interviews. See Table 1 for themes and illustrative quotes.

Theme 1: Limited Knowledge and Awareness

While some providers were knowledgeable about HDV screening and treatment, the majority were not. Participants shared that limited knowledge and awareness about HDV are pervasive, not only among patients and primary care physicians (PCPs) but also among advanced practice providers and specialists (eg, gastroenterologists). These gaps in knowledge extend to prevalence rates, the necessity of screening, available treatment options, and implications for patient management.

Among participants, 4.35% (n = 2) described HDV as relatively common, 28.26% (n = 13) described HDV as relatively uncommon, and 58.70% (n = 27) described it as very rare. An additional 6.52% (n = 3) participants did not provide a definitive assessment of prevalence, explaining that it varies widely based on geography and population, and 2.17% (n = 1) participants reported unfamiliarity with HDV prevalence.

Awareness of bulevirtide and other emerging HDV treatments was limited among most providers. While some were familiar with ongoing clinical trials and investigational therapies, many were unaware of these developments and expressed interest in learning more about upcoming treatment options. For example, one physician who specialized in liver transplantation with 30 years of practice experience noted having heard of certain medications available in other countries that have not yet received Food and Drug Administration approval.

Theme 2: Lack of Clear Guidelines

The absence of clear, accessible protocols and consistent guidelines for HDV screening is a major barrier to effective screening and treatment. Providers face confusion due to varying recommendations from liver societies and the lack of established protocols in their practices. They expressed uncertainty about risk factors, target populations, timing for screening, which tests to order, and how to interpret results. Additionally, some participants also noted uncertainty regarding the next steps if an HDV screening test turns positive.

Theme 3: Operational Challenges

Several operational challenges impede effective HDV screening, including testing procedures, lab issues, and time constraints. Participants highlighted a lack of streamlined testing processes and inconsistencies in the electronic medical records (EMR) systems, which do not always include the necessary HDV tests. Many found ordering screening tests cumbersome, especially when samples need to be sent to external labs, leading to issues like variable insurance coverage, longer processing times, and additional coordination efforts. Labs were reported to struggle with resources, capacity, and efficiency. Furthermore, many providers cited limited time during clinic as a barrier, preventing them from taking comprehensive patient histories and properly assessing who should be screened for HDV, thus risking oversight of critical risk factors.

Theme 4: Cost and Insurance

Some participants identified cost and insurance as barriers to screening, particularly for uninsured patients. High deductibles and uncertainty about insurance coverage have made some providers more reluctant to screen for HDV. Additionally, a few participants were concerned about the potential for false positives and downstream costs.

Theme 5: Provider-Related Factors

Participants noted that provider-related factors that discourage screening, including the perceived rarity of HDV and the ineffectiveness and poor tolerability of current treatments like interferon. This skepticism about the necessity of screening leads to a reluctance to engage in HDV screening and treatment efforts. Some providers admitted to often forgetting to screen for HDV.

Theme 6: Patient-Related Factors

Participants outlined several patient-related factors that impede screening efforts, including unnecessary anxiety caused by false positive results, the discomfort of blood draws, and difficulties in ensuring follow-up compliance. Some participants noted that specific challenges arise among populations dealing with homelessness, low socioeconomic status, or substance use. Screening reluctance is compounded by stigma and discomfort in eliciting or disclosing risk factors like intravenous drug use. Among immigrants, lack of familiarity with the healthcare system, stigma, and language barriers may deter patient follow-up. A few participants observed that disparities in health literacy and healthcare access between US-born individuals and those born internationally exacerbate these screening and treatment challenges.

Recommendations to Improve Screening

The interviews revealed the following nine recommendations to enhance HDV screening and treatment rates (Figure 1 and Table 2).

Theme 1: Provider Education and Awareness

Participants emphasized the need for consistent messaging across various platforms to increase education about HDV among providers. Suggested formats for disseminating information include journal articles, newsletters, webinars, lectures, social media, YouTube videos, conferences, weekly staff meetings, grand rounds, and continuing medical education programs. Participants highlighted the need for a better understanding of HDV’s prevalence, risk factors, and screening criteria, with a focus on primary care to leverage PCPs’ frequent patient interactions. Education on the importance of HBV vaccination and incorporating HDV information into medical school and residency curricula, especially for those entering primary care, were also recommended. Collaboration with medical societies to ensure dissemination of accurate information was advised. In contrast, some providers were skeptical about the need for more extensive HDV education due to its perceived rarity.

Theme 2: Advocacy for Universal Screening

Participants expressed mixed views on the need for universal HDV screening among patients with HBV. Some advocated for universal screening to prevent overlooking patients that should be screened and to reduce stigma, while others believed that screening should be risk-based due to the perceived low prevalence of HDV. In terms of participants’ perspectives on screening approaches, 69.57% (n = 32) endorsed universal screening of all patients with HBV, 28.26% (n = 13) supported ad hoc screening based on specific risk factors, and 2.17% (n = 1) were unsure. It is important to note that although a majority endorsed universal screening in principle, many shared that their current practices still primarily rely on ad hoc screening based on perceived risk.

Theme 3: Improved Guidelines

Most participants stressed the importance of having clear, unified, and updated HDV screening guidelines from major health organizations and medical societies like AASLD. They noted that inconsistencies across different guidelines hinder effective screening practices.

Theme 4: Streamlined Testing Process

Many participants highlighted the need for a streamlined testing process. They suggested implementing automated EMR prompts or flags for HDV screening in HBV-infected patients or when relevant risk markers are detected. Additionally, participants recommended integrating HDV screening into standard lab order sets and templates and implementing reflex testing to ensure efficient and accurate lab procedures.

Theme 5: Increased Access to Screening Tests

Several participants shared that screening tests should be more readily available and accessible, noting the difficulty of ordering HDV screening as send-out tests.

Theme 6: Public Awareness Campaigns

Many healthcare providers suggested launching public awareness campaigns to increase HDV screening rates, utilizing platforms such as social media, billboards, educational pamphlets, and signage in strategic locations such as free clinics and needle exchange programs. Several participants also recommended extending outreach to community hubs and ethnic media and advertising on public transportation.

Participants’ opinions on the scope of public awareness campaigns varied: some advocated for broad campaigns encouraging screening discussions with PCPs, while others favored targeted education for high-risk groups due to concerns over cost-effectiveness and the potential for public confusion and provider burden. Recommendations included dovetailing HDV screening campaigns with existing campaigns promoting HBV vaccination or hepatitis C virus treatment, given the success of the latter campaigns. Additionally, the importance of providing multilingual information, collaborating with advocacy groups, and integrating educational efforts into existing health initiatives was emphasized.

Theme 7: More Research on HDV

Several participants expressed that additional research is required on HDV, particularly concerning its pathophysiology and the development of novel, investigational therapies.

Theme 8: Financial Assistance

A few participants mentioned the need for funding and grants to help cover the expenses associated with HDV screening and treatment.

Theme 9: Accountability Measures

Several participants recommended implementing accountability measures to improve adherence to screening guidelines. Suggested strategies included receiving periodic reports on the number of HBV patients screened for HDV in one's practice and requiring justifications in the EMR for not screening for HDV.

Discussion

Screening for HDV is critical, as HDV infection significantly worsens liver disease outcomes compared to HBV infection alone, substantially increasing the risk of cirrhosis, HCC, liver failure, and death. Early identification through screening enables appropriate monitoring and management, including the opportunity to initiate emerging HDV-specific therapies, which have the potential to alter the disease course. Reflex HDV screening—automatically ordering HDV antibody or RNA testing for all patients with a positive HBsAg result—emerged as a key recommendation from participants to ensure more consistent identification of HDV. If implemented, this approach could potentially help overcome many of the provider- and system-level barriers identified in this study, including variability in provider knowledge, uncertainty around screening criteria, inconsistent test ordering, and EMR navigation challenges. Broader adoption of reflex testing may ultimately support earlier diagnosis and treatment, improving long-term outcomes.

Our findings highlight the need for enhanced provider education, as well as culturally sensitive, accessible healthcare interventions, and public awareness campaigns to increase HDV screening and treatment programs, particularly among high-risk and uninsured populations. Additionally, our results call for a review of structural and policy-related factors impacting HDV screening and treatment, such as official medical guidelines, healthcare access, and resource availability across different practice settings. Although several professional organizations have issued guidance on HDV screening, recommendations remain inconsistent. For example, the EASL and the Asian Pacific Association for the Study of the Liver recommend universal screening of all HBsAg-positive individuals.^6,7 In contrast, current guidance from the AASLD recommends screening only in the presence of specific risk factors or clinical indicators.⁸ This variability may contribute to confusion among providers and inconsistent screening practices across settings. Updated hepatitis B guidelines are anticipated and may include revised recommendations related to universal HDV screening. These evolving guidelines may help standardize clinical practice and enhance provider awareness in the United States. Given mixed views on the need for universal screening, it will be important to study how modified guidelines impact provider behaviors. In addition to guidelines from professional organizations, support from international agencies to raise awareness and standardize clinical practices globally may also be beneficial to increasing HDV screening rates. For example, EASL recommended a revision to the European Code Against Cancer under EU4Health to address the high link between viral hepatitis and cancer, including greater education, prevention, and treatment interventions for hepatitis B, that could ease the risk and incidences of HDV.²¹

Difficulty with test accessibility and ordering procedures was pervasive. Notably, one of the major clinical laboratories in the United States, LabCorp, did not offer hepatitis delta antibody or HDV RNA polymerase chain reaction quantitative testing during the time period when this study was conducted, further compounding provider challenges with screening implementation. Our participants provide several actionable recommendations, which could be accomplished through collective action and advocacy appealing to commonly used commercial laboratories. Streamlining the ordering process would address participants’ concern regarding the excess time required to find and order the appropriate test. Given the variability of EMRs used in different practice settings with unique customization, additional study is needed to better understand the scope of EMR-based ordering difficulties and to propose solutions.

A promising system-level strategy to enhance screening rates involves the implementation of automated EMR prompts. For example, Epic’s “Care Gaps” feature can be programmed to flag the absence of delta antibody testing in patients with a positive HBsAg result, prompting appropriate follow-up. As health systems have the capacity to customize these alerts, optimizing EMR-based notifications represents a pragmatic and effective approach to reduce missed screening opportunities. Utilizing EMRs to identify this specific care gap may represent one of the most feasible interventions to improve identification of at-risk patients.

Low perceived HDV prevalence and a sense of futility are important subthemes that must be addressed through educational programs that are targeted by specialty and strategically disseminated. Participants reflect concern about limited treatment options and the potential for severe side effects, which may lead to increased patient anxiety and suffering. This, coupled with concerns regarding potential patient financial liability from HDV screening, suggests that patient-centered beliefs strongly contribute to low HDV screening rates,¹⁰ rather than mere forgetfulness, lack of knowledge, or uncertainty. Financial burden commonly affects patients with chronic liver disease,²² thus ensuring that there is insurance coverage or industry support via philanthropic grants to offset the cost of emerging HDV therapies will be critical. In addition to enhancing screening practices and EMR integration, promoting access to clinical research opportunities for HDV patients emerged as a key area for improvement. Expanding clinical trial infrastructure and referral networks would ensure that patients identified through screening have pathways to emerging therapies.

While other studies have addressed the perspectives of individuals living with hepatitis D,²³ this study is the first to present detailed perspectives from the vantage point of health care providers situated in geographically diverse practice settings. Qualitative interviews are subject to recall bias and social desirability bias, which is a limitation. We attempted to mitigate the latter by utilizing an interviewer not known to participants and informing participants that all data would be deidentified. An additional limitation is the potential for selection bias, as participants were recruited from a cohort that had previously completed a survey study on HDV knowledge and screening practices. These individuals may be more engaged or informed about HDV than the broader population of gastroenterology, hepatology, internal medicine, infectious diseases, and family medicine providers, particularly those practicing in community-based settings. As such, the knowledge gaps and system-level barriers identified in this study may represent a conservative estimate of the broader challenges in HDV screening. Although our sample was skewed with an inclusion of more doctors (n = 35) than physician assistants (n = 6) or nurse practitioners (n = 5), this sample closely represents the proportions of professionals caring for patients living with HBV/HDV. We aimed for equal geographic representation but had more participants from the Northeast and South compared to the West and Midwest. Despite this relative imbalance, we reached thematic saturation.

Finally, most participants were subspecialists employed in academic medical centers and outpatient clinics, rather than community hospitals, private/group/hybrid practice, or Veterans Affairs medical centers. However, we did have representatives from each group. Additional study is needed to better understand how the perspectives of community gastroenterologists and PCPs might differ. Depending on practice location and insurance constraints, which can limit access to subspecialty hepatology care, these providers could care for a greater total number of HBV patients than academic gastroenterologists and hepatologists. Furthermore, we would anticipate that community-based subspecialists and primary care providers would experience even more challenges when screening for HDV given limitations of using community laboratories. Although we attempted to procure a balanced perspective in our study, our participants’ experiences and perceptions may not fully represent all healthcare settings or providers in the United States or worldwide.

Through this study, we gained a more comprehensive understanding of provider- and system-level challenges in HDV screening than was previously available. Our participants identified actionable strategies to improve screening and care delivery, including implementation of HDV testing among all individuals who have tested positive for HBsAg, expanded provider education on HDV and its consequences, optimization of EMR-based prompts to support clinical decision-making, and increasing awareness of and access to research opportunities for patients with HDV, ensuring they are connected to new and emerging therapeutic options. Some of these recommendations could be implemented immediately at the level of the individual provider or practice level. It is important to note that some recommendations may not be applicable for all providers or practice settings; thus, providers should identify which recommendations can be feasibly implemented. Future research should focus on developing and evaluating educational interventions for healthcare providers to enhance understanding of HDV, clarify screening guidelines, and promote best practices. Additional study on which patient-related factors specifically affect HDV screening vs general challenges with access to care would be beneficial to target future interventions. Finally, the feasibility of incorporating automated prompts into the EMR and streamlining the testing process warrants further investigation.