Hep B Blog

Category Archives: HDV

advocacy, HDV, Hepatitis D Advocacy, Hepatitis Delta (HDV)

An Interview with Hepatitis Delta Advocate, Dr. Carla Coffin

Since 2016, the Hepatitis B Foundation has run a program called Hepatitis Delta Connect which aims to increase awareness of hepatitis delta and support for those living with the virus. For this month’s blog post, we sat down with Dr. Carla Coffin, a hepatologist in Canada, who is active in the hepatitis delta space.

Please introduce yourself and describe what you do and where you work.

My name is Dr. Carla Coffin, and I am a hepatologist at the University of Calgary in Alberta, Canada, I am a clinician scientist who does research on hepatitis B and this year I am the president of the Canadian Association for the Study of the Liver. Calgary is the founding/coordinating site for the Canadian Hepatitis B Research Network, which helps lead a collaboration of researchers, scientists, and practitioners across Canada for hepatitis B research and advocacy.

How common is hepatitis delta in your location or nationally?

That is an excellent question because until relatively recently, we didn’t know that much about how common hepatitis delta was in Canada. Most studies were single-site, single-center studies, showing about 1% prevalence overall in people living with hepatitis B. Then the Canadian Hepatitis B Research Network in collaboration with the National Microbiology Lab and the National Reference Lab in Canada did a study, led by Dr. Carla Osiowy, that showed, based on a retrospective screening of cases that were referred for hepatitis delta testing, that the prevalence was about 3% overall. Now, there’s more recent data that is consistent with that approximation of about 3%. We are also conducting a study that shows that for people who are being referred for delta screening, their overall positivity is about 4%. These are specific studies, but if you are just looking at universal screening rates of everyone who is living with hepatitis B who is potentially at risk for hepatitis delta, and not necessarily pre-identified, it’s much lower, maybe only about 1% or 2%.

What are the current screening recommendations and protocols in Canada for hepatitis delta virus (HDV)?

Historically, the recommendations from our major guidelines have been risk-based screening. So, people that are coming from areas where we know hepatitis delta is endemic. People that may have other risk factors such as a history of injection drug use or clinical characteristics that might trigger the clinician to suspect hepatitis delta co-infection. But based on that, I think that people are missed or are not diagnosed, so there’s inaccurate epidemiology just on risk-based screening. Our updated hepatitis B guidelines, which hopefully will be published in 2025, are more consistent with other expert recommendations to do universal screening. So at least a single, one-time test will be recommended for all people living with hepatitis B, to screen for hepatitis delta. And many of our laboratory partners agree with these recommendations. So hopefully there will be a change in the near future for that.

Do you think the reported prevalence is accurate or are people missing?

I would say that the current reported epidemiology of about 2 to 3% is likely to be accurate, but without having a robust universal screening program and robust reporting of hepatitis delta-positive cases, then I can’t say that with 100% confidence. One of the metrics that the Public Health Agency of Canada is advocating for is to have more robust data collection on hepatitis D epidemiology. That’s one of the calls by Action Hepatitis Canada, which is an advocacy group.

So, I think the epidemiology is accurate based on the data we have, but I can’t be 100% confident until we do more robust studies.

What do you think could help to address some of the underdiagnosis of hepatitis delta globally?

We need universal screening to ensure that people are diagnosed and not just rely on risk-based testing. We talk about knowing where hepatitis delta is endemic, but we should also recognize that there are probably countries where the prevalence is higher, but because of a lack of screening, we don’t know where it is actually endemic.

Even in my practice and just this week, we came across a patient that had been followed in our clinic for 15 years with hepatitis B and we only diagnosed this person with hepatitis delta recently, because we hadn’t screened it before.

And I think the other important thing is to increase awareness among health practitioners. A specialist might know about hepatitis delta, but a primary care provider or non-hepatologist would be left less aware. Increase education of healthcare practitioners to say, you know, if your patient has hepatitis B, they should be screened for hepatitis delta.

What do you usually do to help patients manage hepatitis delta?

Well, I think the first thing is you need to explain as clearly as possible exactly what hepatitis delta is and how you get hepatitis delta. How do you prevent it from spreading?

Explain how it’s transmitted by sharing blood and body fluids, highlighting that if you get the vaccine for hepatitis B, that protects you against both B and delta. Then explain what delta can do to your liver and how it can increase your risk of getting liver damage, or liver scarring or cirrhosis, how it increases your risk of getting liver cancer, and the importance of having regular checkups on your liver. So, regular blood tests and regular ultrasounds for monitoring for liver disease and for liver cancer. A lot about management is empowering the patient and giving them educational resources. Then the other thing is to discuss the treatments. There is only one treatment approved for hepatitis B in Canada, and you can use it for hepatitis delta, and that’s interferon. That’s the only thing we can currently use to treat hepatitis delta.

If/when a new drug is approved in Canada, do you think distribution and uptake will be straightforward or do you perceive challenges?

Yes, there will be many challenges. Part of it stems from underappreciation of hepatitis B as well as hepatitis delta. So, if a new drug is approved, it may be a challenge just to raise awareness about it.

And the second thing is that health care is federally funded, but the funding is then sent to each jurisdiction. The provinces and territories decide how healthcare funding is spent, and then there’s a complex approval process. It starts with Health Canada approval and then there’s this pan-Canadian drug agency called CADTH, the Canadian Agency for Drugs & Technologies in Health, that reviews the medication and sees whether or not they would recommend it. Then each provincial agency looks at the review by CADTH and decides if they want to have it on the formulary.

So, it could be time-consuming, complex, and challenging because of these factors.

Can you describe some of the advocacy efforts in which you have been engaged on hepatitis delta at different levels, and with different stakeholders?

Yeah, so I’m happy to say we’ve been having some success with advocacy. So different stakeholders and partners include Action Hepatitis Canada, the Canadian Liver Foundation, and our professional organization, the Canadian Association for the Study of the Liver. Activities we have done include going to Parliament Hill in Ottawa and holding our Annual Viral Hepatitis Elimination Day on May 9th. We’ve done that now for three years. With the help of all these partners and stakeholders, we have been engaging various governments (so government ministers at the provincial level and at the federal level), and also working with our federal health agencies (so the Public Health Agency of Canada) and having discussions with them to increase the messaging about hepatitis delta.

Are there any messages about hepatitis delta that you would like to share with policy or decision-makers?

I think you need to start with the patient’s voice. What I found most striking when we were meeting with the different policy decision-makers and government officials was that the physicians or the experts could talk about hepatitis B and talk about hepatitis delta and you didn’t see the same impact, but we brought patients with us when we had our meetings and when the patients spoke up and talked about their lived experience, you could really see their story having a strong impact. Then, also try to support the work of our partners.

What are some possible programs or initiatives that can help raise the profile of hepatitis delta and improve participation in the care cascade?

A lot of the people affected by delta are non-Canadian born, so there are a lot of challenges in navigating the healthcare system and language barriers. If we had more in terms of language or translations, I think that would be a good way to increase participation in healthcare and potentially raise the profile. The second is the education of healthcare practitioners, going beyond the specialist, and talking to primary care and family doctors.

Also, perhaps starting at the community level, at a non-academic center to raise more awareness about hepatitis delta and involving people with lived experience. But that’s a bit more difficult because there are so many, at least in Canada, challenges with understanding the language and understanding that patients often have many other challenges that it’s hard for them to think about their health care.

Do you have any final thoughts on hepatitis or hepatitis delta?

There’s been a lot of progress on hepatitis B with the drugs that we have currently, the effective nucleoside analogs, and with the hepatitis B vaccine, of course. It’s a remarkable vaccine, but we need more research and investment in both basic science research to try and find a cure for hepatitis B, and more public health research and investment to reach those that are living with hepatitis B, to provide them treatment and limit financial barriers. Also, more research and investment for hepatitis delta and testing. There’s not even a standardized test for delta. So, my final thought would be that we’ve done a lot, we’ve made progress, but there’s still more work to be done, and we need more government and industry funding.

CAB Corner, Clinical Trials, HDV, Hepatitis Delta (HDV), Living with Hepatitis B

Lived experiences of clinical trials and how patient insights can improve equity in process and outcomes

 

 

 

 

Authors: Lori Scott, Amanda Goldring, Joe Balestreri, Philip Kwame Yeboah, Kenneth Kabagambe, and Prince O. Okinedo  

Patient involvement in research means they are included as active partners in all stages of the research process. In other words, patient involvement ensures that research is carried out with patients, instead of research being done to patients [1].  

 

Patient involvement is essential throughout the drug development and clinical trial process to ensure patients’ clinical needs and preferences are met [2]. When clinical trial teams do not involve patients as research partners to identify appropriate research outcomes and co-create study designs, the teams may fail to achieve meaningful outcomes. More and more researchers are realizing that the personal experiences of patients and their caregivers are not just useful, but vital to the design of clinical trials. 

 

Patient participation in clinical research is crucial for informing patient recruitment and retention efforts that can ultimately speed up the development and potential market availability of medicines and diagnostics [3]. In the end, patients are the intended recipients of the products of clinical research, and if patients are actively involved in research, they can effectively improve outcomes. 

 

The following four sections share real life stories and lived experiences of individuals trying to participate in clinical trials, and the challenges they have faced. The patients and caregivers who contributed to this blog have personal experiences with applying for, enrolling in, and being rejected from clinical trials, and know of the treatment consequences when patients are not involved in their care plans. Based on their experiences, they have suggested many ways to incorporate the patient voice into drug development and clinical trial design, from recruitment, enrollment and retention methods to informational materials for patients, to help industry and academia develop more accessible clinical trials and research efforts. 

 

Please note: Following the four accounts of personal experiences, there are seven specific suggestions for researchers.   

 

Lori’s lived experience: Challenges identifying and applying for clinical trials (2018) 

There is no clear pathway for patients when trying to find and apply for clinical trials, and much of the effort is placed on the patient to move through the process.  

 

Currently, it seems the internet search bar is the best option for patients trying to join clinical trials, and recruitment is not happening at the local level in communities and even in doctors’ offices. This process places a significant burden on the patient and needs to change.  

 

My daughter’s diagnosis of hepatitis B, hepatitis D and other rare digestive diseases did not come with a map. We had to start with the internet and do our own research. I would work all day and research all night; I was in a fight for my daughter’s life. We learned about some potential clinical trials through the Hepatitis B Foundation’s Clinical Trial page and how to apply for study participation. When my daughter applied for a clinical research program with the National Institutes of Health (NIH), I had to figure out the whole process from finding information to applying and getting screened. 

 

We were excited when she was accepted for the first phase of the trial, but as I understood later, my daughter’s study group was one of the first of this trial. The trial was not well organized, and it seemed that the research team was not cohesive. It seemed that the staff did not know if the patients had full understanding of all that would happen in the clinical environment. Participants involved in the consent process need to understand that research is distinct from clinical care. Research eventually benefits society rather than the participant. It is also necessary to understand expectations and risks involved in participation, and that someone knowledgeable is available to go over questions and concerns before the consent signature. 

 

While the travel was well coordinated, it was difficult for my daughter due to her frail physical condition. When we arrived, some of the specialists assigned to her care were on vacation or otherwise unavailable, which was heartbreaking as we were informed of my daughter’s very full itinerary before planning our trip to the center, to ensure she would receive all planned evaluations. We had planned specifically for these two days and that somehow did not happen. These physicians were vital to the study process, and the evaluations should have been postponed until those key people were available. 

 

We returned home with little communication from the program after their testing, which they told us would be normal. A year later, we received a letter from the organizers, stating that they were releasing her from the study but would keep her data in the system. 

Reflecting on this experience, I was disappointed in the way the trial was organized. If there was a patient navigator, or clear informational sources, we would not have had to guess what was happening next for the entire time we were at the research site. Because it wasn’t well explained, we had unmet expectations of the study. Despite these shortcomings, we are glad to have participated and felt we learned so much about research. 

By gaining a deeper understanding of patients’ and caregivers’ lived experiences and challenges, organizations offering clinical trials can become a true asset, providing the valuable data needed for future research. 

 

Amanda’s lived experience: Clinical trial rejection (2020) 

It was only a couple of months after my hepatitis B diagnosis that my liver nurse called to ask if I would be willing to apply for a clinical trial. The trial team was trying to find a functional cure for HBV. She said that she could not guarantee that my application would be successful, as she did not know the criteria for acceptance, but it was worth a try. 

I sent off my application form and waited to hear back.  

 

Initially, I was very excited at the thought of participating in a trial. Even if the trial came to a dead end, it could possibly be another step towards a functional cure. I watched for the post each day, hoping for an acceptance letter. As time went on, I was sure that I had a place on the trial. Surely, if I did not meet the criteria I would have heard back almost right away. To save disappointment, it would have been better for the “acceptance criteria” to be transparent, either at the start before my nurse had become involved, or at a later stage on the application form. In this case I was given no patient-facing materials. Surely this should be a standard requirement. 

 

Time passed and eventually the letter I had waited for dropped through my letter box. On opening it my heart sank–it was a rejection letter. Due to being diagnosed with Crohn’s disease (a type of irritable bowel disease that makes your digestive tract become swollen), I was not suitable for the trial. The letter tried to let me down gently, saying that maybe I would be suitable later. However, it gave me false hope and for months I hoped that a letter would arrive inviting me to participate in the trial that did accept Crohn’s patients. Eventually, I realised that this letter was never going to come. My world, which was already dark, felt darker. I felt that society was rejecting me and now the drug trials were too. Drug researchers should consider patients’ feelings when rejecting their application. They should implement quick responses and avoid using language that may give false hope for future acceptance into another clinical trial. 

 

Thankfully, I have moved on from this dark period in my life. I have accepted that I will probably never be eligible for a clinical trial, as a functional cure seems to rely on strengthening the immune system. My Crohn’s treatment relies on suppressing the immune system. It would have been kinder, in the long run, not to give false hope. An explanation as to why Inflammatory bowel disease was excluded would be far better than “maybe at a later date.” As patients, we are used to hearing stark news and although it might be painful to hear, we eventually do accept it – we have no choice. 

 

There is hope after being rejected for a trial. There will possibly be other drug trials to apply for and if not, the pot of gold at the end of the rainbow will eventually be a functional cure for this or the next generation. 

 

Researchers must consider patients’ feelings when rejecting their applications. Implementing quick responses is not just a matter of efficiency; it also shows respect for the patient’s time and effort. 

 

Joe’s lived experience: Clinical trial participation (2013 to 2019)  

When I signed-up for the National Institutes for Health’s (NIH) clinical trial to find a treatment for hepatitis delta in 2013, I didn’t know how it would affect my life overall. I was focused on getting help. 

 

The NIH was accommodating in many ways concerning my practical needs. For U.S.-based patients in my trial, airfare, lodging on campus, and most land transportation was paid for by the NIH.  

 

But there were many challenges to being in a trial far from home. Looking back, I figured each of my 70 round trips from California to Washington could cost me $100-200 in lost wages and travel expenses. There were also challenges getting to D.C. for weekly appointments, which required 16 to 20 hours of travel round trip. These visits were crammed with many weeks’ worth of tests, scans and doctor appointments. Sometimes, poor communication from the NIH led to confusion about my travel arrangements. Other times, my symptoms were so bad that I couldn’t bear a long plane ride plus getting to and from the airport. 

 

Communication with the NIH was good but sometimes lacking, especially as it was difficult getting my hepatitis delta test results. Oftentimes, I did not receive clear and adequate explanations of my results.  

 

If I were involved in redesigning my study, I would have urged the researchers to have a better understanding of what patients and their loved ones go through just getting to the NIH, including the financial, physical and social costs, as well as time commitment. When clinical trials are informed by patients, other patients in the community are more likely to volunteer for trials AND are more likely to stay committed to participating, as the challenges mentioned above (personal hardships, communication issues) have been accounted for during the clinical trial design. 

 

Philip’s: How patient involvement in research can enhance hepatitis care in Africa 

Patients in Ghana are not involved in clinical research, despite existing research infrastructure. There are many clinical research institutions, including the Ghana I Noguchi Memorial Institute for Medical Research and Kumasi Centre for Collaborative Research. These are the same research institutions that train the doctors who handle hepatitis B.  

 

Linking it to my late brother’s story, I remember when Komfo Anokye Teaching Hospital in Kumasi, Ashanti region, Ghana, booked my brother who was living with hepatitis B on Aug. 17, 2017, to come for treatment on Sept. 4, 2017. Because there are a limited number of doctors who were available to treat people living with hepatitis B, my brother had to wait for weeks for a doctor’s appointment. During this waiting period, I updated the hospital on my brother’s deteriorating condition many times, but they insisted that he must wait until the booked date. At exactly 8:15 a.m. on Tuesday morning, 5th September 2017, heartbreakingly, I saw my brother Emmanuel, also known as Action man, giving his last breath. Because there was no patient involvement in care plans in Ghana, there was nothing to help my brother’s condition, as he was diagnosed too late, and there were no clinical trial opportunities to explore (to our knowledge), despite the apparent need. If those living with hepatitis B had more say in their care plan, they would be able to communicate directly with researchers about their conditions and be guided accordingly, and appropriately for their individual cases. 

 

After my brother’s demise, our immediate family members went to get tested for hepatitis B. We all tested negative for hepatitis B infection, and we took the vaccine. Based on these experiences, I have taken it upon myself to educate the public about the deadly but preventable hepatitis B infection on social media platforms and radio stations. Currently, I am the Ashanti Regional Representative for Hepatitis Foundation of Ghana and a member of the Hepatitis B Foundation’s Global Hepatitis B and D Community Advisory Board.  

 

People with lived experience have insights that can help inform researchers and clinical trial developers in their research efforts and encourage them to seriously consider patient inputs during all steps in the drug development process, from clinical trials to developing patient care plans.  

 

Kenneth: How patient involvement in research could have future impact on care/treatment practices 

Patient involvement in research can significantly enhance African healthcare practices by promoting more effective, relevant, and culturally sensitive interventions. This method reflects African communities’ cultural, social, and economic realities, ensuring that findings and recommendations are viable for local implementation. Patients can contribute insights into critical health challenges, such as infectious diseases, maternal health, or non-communicable diseases like diabetes and hypertension. 

 

Involving patients in research increases their understanding of their diseases, treatment options, and the importance of adherence to medical guidance, leading to better health outcomes [4]. They can also function as advocates and educators, increasing awareness and debunking misconceptions about diseases and treatments. 

 

Research that includes patient involvement can establish treatment protocols and care practices better adapted to the local environment, promoting comfort, dignity, and patient choices [5]. Patients engaged in inclusive research are more likely to trust and engage with the healthcare system, leading to higher participation in health initiatives, better treatment adherence, and greater uptake of preventative measures [6]. 

 

Research that is co-led with patients can have a dramatic influence on policymakers. By providing data founded on the real-world experiences of persons afflicted by diseases, patient-centered research can drive the development of policies that prioritize patient needs and assist in implementing more successful health services. 

 

In conclusion, the revolutionary potential of patient involvement in research cannot be more strongly emphasized! By ensuring that healthcare practices are more relevant, culturally sensitive, and aligned with the population’s needs, this approach has the power to significantly improve the quality of care, foster greater trust in the healthcare system, and ultimately lead to better health outcomes and more resilient healthcare systems across Africa. 

 

Suggestions 

Research using patient involvement led to more meaningful socio-economic and cultural outcomes, as patients identified issues of which researchers were not previously aware [7]. When patients are involved throughout the drug development/clinical trial design process, they can inform researchers of best practices to disseminate results among the participants and greater patient community, as they can suggest appropriate communication methods to ensure comprehension [8, 9]. Similarly, patients can co-present results at conferences [10], which can increase the greater patient community’s trust in research, and potentially increase their willingness to participate in future clinical trials, or other research endeavors. 

 

Take home suggestions for researchers:  

1) Recognize the hardships and costs of long-distance travel for patients. Find ways to alleviate this by, for example, allowing patients to get tests and scans closer to home. 

2) Find ways to help patients with the incidental costs of the trial, not otherwise covered. For example, connect patients with educational resources about financial assistance programs and fundraising methods.  

3) Improve timely communication between trial staff and patients. 

4) Properly educate and inform potential study participants on the study’s required activities.  

5) Allow study participants to have access to their personal trial data and study statistics. 

6) Recognize patients as citizen scientists, as their participation is critical to research advancement, as they provide careful and specific observations. Researchers must keep in mind that patients are not just test subjects. 

7) As important as it is to get the patient to understand clinical trial requirements, researchers should also make the effort to educate the close family members of consenting patients. Offering moral support, especially in communal settings like Africa, is critical to enhance acceptance of clinical trials and research endeavors. 

 

Resources 

  1. National Institute for Health and Care Research. (n.d.). I want to help with research. [Accessed from:  https://www.nihr.ac.uk/patients-carers-and-the-public/i-want-to-help-with-research/] 
  2. Arumugam, A., Phillips, L.R., Moore, A., Kumaran, S.D., Sampath, K.K., Migliorini, F., Maffulli, N., Ranganadhababu, B.N., Hegazy, F. & Botto-van Bemden, A. (2023). Patient and public involvement in research: A review of practical resources for young investigators. BMC Rheumatology, 7(2). doi: 10.1186/s41927-023-00327-w 
  3. Anderson, A., Borfitz, D., & Getz, K. (2018). Global public attitudes about clinical research and patient experiences with clinical trials. JAMA Network Open, 1(6), e182969-e182969. doi: 10.1001/jamanetworkopen.2018.2969 
  4. Shea, L., Pesa, J., Geonnotti, G., Powell, V., Kahn, C., & Peters, W. (2022). Improving diversity in study participation: Patient perspectives on barriers, racial differences and the role of communities. Health Expectations. 25(4):1979-87. doi: 10.1111/hex.13554 
  5. Wind, A., van der Linden, C., Hartman, E., Siesling, S., & van Harten, W. (2022). Patient involvement in clinical pathway development, implementation and evaluation–A scoping review of international literature. Patient education and counseling. 105(6):1441-8. DOI: 10.1016/j.pec.2021.10.007 
  6. Mulqueeny, D.M. & Taylor, M. (2022). Patient-centred care: Reality or rhetoric—patients’ experiences at ARV clinics located in public hospitals in KwaZulu-Natal, South Africa. AIDS research and therapy. 9(1):41. DOI: 10.1186/s12981-022-00463-2 
  7. Shen, S., Doyle-Thomas, K. A. R., Beesley, L., Karmali, A., Williams, L., Tanel, N., & McPherson, A. C. (2017). How and why should we engage parents as co-researchers in health research? A scoping review of current practices. Health Expectations: An international Journal of Public Participation in Health Care and Health Policy, 20(4), 543–554. https://doi.org/10.1111/hex.12490  
  8. Beier, K., Schweda, M. & Schicktanz, S. (2019). Taking patient involvement seriously: A critical ethical analysis of participatory approaches in data-intensive medical research. BMC Medical Informatics and Decision Making, 19(90). doi: 10.1186/s12911-019-0799-7 
  9. Maccarthy, J., Guerin, S., Wilson, A.G. & Dorris, E.R. (2019). Facilitating public and patient involvement in basic and preclinical health research. PLoS One, 14(5): e0216600. doi: 10.1371/journal.pone.0216600 
  10. Jackson, T., Pinnock, H., Liew, S.M., Horne, E., Ehrlich, E., Fulton, O., Worth, A., Sheikh, A. & De Simoni, A. (2020). Patient and public involvement in research: From tokenistic box ticking to valued team members. BMC Medicine, 18(79). doi: 10.1186/s12916-020-01544-7 

HBV, HDV, Hepatitis B Awareness, Hepatitis Delta (HDV), Liver, Living with Hepatitis B

Nargis Speaks about Living with Hepatitis Delta

The hepatitis delta virus is a sub-virus of hepatitis B that depends on the hepatitis B virus to survive and reproduce. Hepatitis delta affects between 5% and 10% of people living with hepatitis B, and can quickly progress to a more serious and advanced liver disease than HBV alone. Since 2016, the Hepatitis B Foundation has coordinated a program called Hepatitis Delta Connect, which works to raise awareness of hepatitis delta; promote screening, research, and management of the virus; and provide support to individuals living with and affected by the disease. This includes capturing the lived experiences of hep D. This month, Ariana, an intern at the Hepatitis B Foundation, interviewed Nargis, a resident of New York, who is living with hep B and hep D, about her experiences of the viruses, from diagnosis to management. We thank Nargis for sharing her story!

Ariana: Thank you very much for joining today! When were you initially diagnosed with hepatitis delta?

Nargis: I was diagnosed in 2005. I did my blood work at the end of 2005 and got my result at the beginning of 2006. The reason why I went to do the blood work is because I had very severe flu-like symptoms.

Ariana: How did you find out you were living with hepatitis delta?

Nargis: I was out of the city for a trip, and felt sick after, so I immediately returned to the city and did blood work and found that it’s hepatitis D. I was surprised because I know if you don’t have hepatitis B, hepatitis D would never exist in your body. 

Ariana: How did you initially feel about it?  

Nargis: To be honest, I was depressed. It happened during the best time of my life when my career was at a high point, and I’m feeling like I’m enjoying life and everything is fine. All the difficulties in my life were gone. During that time, I was at the top of the level of my career and I could do something for myself and for my family. And I had big plans, and when I was diagnosed with hepatitis B, all my plans just collapsed. My doctor just straight up told me that I’m lucky to have Hepatitis B and D, not C. They did not give me any kind of psychological support, and I was extremely depressed. Thank God for my family and my husband for being there to support me always.

I’m originally from Dushanbe, Tajikistan. It’s a small country in central Asia. Unfortunately we don’t have enough good medicine to help with this kind of thing, as the government is not supporting nor providing any kind of medication. The medication I needed had to be ordered from Russia to bring here, and was very expensive. The prices go up and down. And, this one is also not guaranteed to work. I got interferon, but it didn’t work for me. After one month of injections, I got very, very sick. And the doctor decided to stop it. 

Ariana: How do you think this disease has impacted your physical state?  

Nargis: Mostly it’s the mental changes when you are becoming depressed, but when you’re starting the treatment, you feel so weak. I had severe weakness, fatigue. I also had GI (gastrointestinal) problems as well.

You get kind of the nausea, no vomiting, just the nauseous feeling. But in the morning, you are feeling fatigued. You are always the one to sleep and have joint pain. Now I’m just feeling kind of the joint pain, but when I’m starting to work or do some activity, I get tired. I always feel the fatigue, you know, or the fatigue sometimes is so much, I don’t want to even do anything, but I always push to do things I should do. I often get bad pain.

But I’m always appreciative, you know, as I am still alive, and I have to thank my family for that.

Thank God. My third daughter was checked for hepatitis B and D too. Thank God, she got her vaccination, which is making us happy. Now I have four kids, and I’m calling my fourth child my miracle child, she gives me so much happiness. 

And all of them, all my kids are free from hepatitis B. They got all the vaccinations, my husband as well. And routine family life and my job are like keeping me in the life, making me happy, and I’m not thinking so much about my hepatitis. Thank God, I have my arms, my legs and I can eat, I can walk, I can see. This is more than enough to keep me happy.  

Ariana: Why is raising awareness of hepatitis delta important? 

Nargis: It’s important for people to know about it and I’m talking about my experience. I didn’t catch it from receiving medical care in my country, but a lot of people don’t know about this one and, if you don’t know, you don’t pay attention. We must be careful with  needles [which can possibly transmit hepatitis delta].

It is important to make information booklets, allowing patients to talk about their experiences, finding people similar to us, and we are people, we still have this disease, but we are very active, we can work, we can sing, do something good. 

It is better if you support each other as well, every person is important in this life, every person can be very important for somebody else.

People must know. If you’re somebody who doesn’t have education, maybe there’s some pictures with a simple explanation to tell them. It really works because, when HIV and AIDS existed in this world last century, the people didn’t know so much about it. And when the other foundations and the people and mass media started to get to work and explain, and gave out the information booklet, people are starting to pay attention now. And I’m thinking this can work for hepatitis as well.  

Ariana: What do you wish more people knew about this disease? 

Nargis: It’s hard to always be healthy. I wish for everybody to be healthy, but it’s now hard to be healthy, because you never know where you can catch hepatitis…And just so I can wish for people to keep their eyes open and not be afraid.

Keep your eyes open. Where are you going? What are you eating? Which kind of medical offices are you going to? If you have the blood transfusion, using the needles or something, or some kind of tools used for dental procedures, just to make sure all of them, they’re sterilized and clean. 

Be open mentally and healthy. It will help you in this kind of situation as well. You know, talk with somebody if you can talk with some of your family members or with people from outside. I’m an open person, and for me, it’s very, very helpful.

Also, Dr. Kushner invites me to Zoom classes where I hear about the Hepatitis B Foundation, the kind of research you have, what the people around the world are trying to do and how to help patients. It’s given me support. It’s given me kind of the hope that not everything is lost and I believe that some medication will be invented soon in the world to help the millions of people with hepatitis B and D. 

Ariana: What resources do you think you would have wanted initially when you got diagnosed with hepatitis delta?  

Nargis: Getting the right medication for people is very important. Insurance companies should help the patient to get the right medication. And also, I’ve been in a research study and the first research study I got is a medication for hepatitis B and D. The doctor teams are working specifically with this kind of patient when the patient goes to the hospital and does the blood work to see the level of the hepatitis B and D and also the liver enzymes. 

Also patients are depressed and always need some support group, maybe some social workers can closely work with people who have hepatitis B and D.

Ariana: Do you think there’s anything else you would like to share about your experience? 

Nargis: I would like to tell the people who have hepatitis B and D, do not be afraid. The doctors are working, and the research team is working hard. We’re not alone in this world. The Hepatitis B Foundation and many others are working on this problem. Do not lose hope. Be powerful, be happy, thank God we are alive, and support each other.

Ariana: Awesome. Thank you so much for sharing your insight and experiences with us today!

HDV, Hepatitis D Advocacy, Hepatitis D Drug Development, Hepatitis Delta (HDV)

The Provider’s Perspective on Hepatitis Delta: A Conversation with Ilan Weisberg, MD

Dr. Ilan Weisberg is a highly acclaimed gastroenterologist and hepatologist currently serving as the Chief of Gastroenterology and Hepatology at New York-Presbyterian Brooklyn Methodist Hospital. He shares the Hepatitis B Foundation’s enthusiasm for advocacy and education surrounding hepatitis B and D, and was eager to provide the perspective of a healthcare provider on the current state of hepatitis delta screening and management, as well as some common misconceptions.

A Shift in Provider Awareness and Knowledge

One of the first topics Dr. Weisberg spoke about was how unaware he was about hepatitis delta until recently. He discussed the ongoing issues with a general lack of knowledge about hepatitis delta in the United States, and how this is the most common reason for many of the current challenges seen today. When asked what led to his and other providers’ shift in knowledge, he credited the improvements with hepatitis C awareness and treatment with some of the shift, as well as the potential for new treatments for hepatitis B and D. “Every time there is a promise of a treatment or a cure or intervention, then I think it helps engender more enthusiasm for screening.”

Hepatitis Delta Prevalence and Screening Practices

Dr. Weisberg sees hundreds of patients who are living with hepatitis B virus (HBV). New York, and especially Brooklyn, have so many cultural communities coming from countries where hepatitis B is common. Hepatitis D is a much smaller percentage of his patient population. Dr. Weisberg was a co-author on a study that looked back through electronic medical records (EMRs) for all hepatitis B surface antigen positive (HbSAg+) patients at his former health system to identify how common hepatitis delta virus (HDV) testing and prevalence were. Across the entire health system only about 12% of HbSAg+ patients were tested for delta and among those individuals there was a 4% positive rate for HDV (Nathani et al., 2023).

One particularly concerning part of that study for Dr. Weisberg was the overall low rates of hepatitis delta screening. He notes that it is difficult to keep health care providers motivated to screen when the number of those with hepatitis delta is so low, and that creative solutions like automatic EMR suggestions may increase the likelihood of testing. About three years ago at his former clinic, Dr. Weisberg standardized a protocol for screening every existing and new patient living with hepatitis B for hepatitis delta at least once. This protocol is still being used in his current health system. “Even though the event rate is low, the clinical importance of finding these patients [is] very high” and he hopes that this approach will be widely adopted to more closely align with European Association for the Study of the Liver (EASL) recommendations compared to the current risk-based approach of the American Association for the Study of Liver Disease (AASLD)(EASL, 2023; Terrault et al., 2018). Discussions on changing these American recommendations have been in circulation and plans to update them should be realized in the near future.

Dr. Weisberg believes that one of the reasons for the low testing is that hepatitis delta is considered a “rare disease” in the United States. He notes that the major differences in the number of cases among different countries means that one study in a specific geographic area cannot be generalized to the entire global prevalence.  He hypothesizes that if there was true and accurate prevalence data across the globe, the number of cases would be higher than those estimated in the U.S.  and globally today. One of the challenges in providing accurate prevalence data is knowledge about appropriate testing, which Dr. Weisberg recalls encountering in his clinical career. When he arrived at his former health system, they were only testing for hepatitis delta antigen rather than the hepatitis delta antibody (anti-HDV), which is the appropriate initial test to perform. True prevalence rates are important for improving our understanding of who is affected by hepatitis delta, and with new therapeutics on the horizon, it is vital to identify patients who are hepatitis delta-positive so that they can participate in trials and be ready to receive treatments once approved.

Thoughts on Universal Reflex Testing

Dr. Weisberg mentioned that his current health system does not have the HDV test set up as a reflex test (automatic testing for HDV when one tests positive for HBV, using the same blood sample) straight from HbSAg+ to anti-HDV and from anti-HDV to confirmatory HDV RNA, but they are working on getting that established. “In a place like Brooklyn where we have enormous populations from hot spots of endemicity for delta, like Moldova and Mongolia, it might be very cost-effective, but in other parts of the country it may not be, and it is hard to have a universal strategy that is not universally cost-effective.” He also highlighted the need to be able to reliably check across databases to avoid repeated testing upon new emergency room visits, providers, etc.

Risk Factors for Hepatitis Delta

According to the AASLD, identified risk factors for hepatitis delta include persons born in regions with reported high HDV endemicity, persons who have ever injected drugs, men who have sex with men, individuals living with hepatitis C (HCV) or human immunodeficiency virus (HIV), persons with multiple sexual partners or history of sexually transmitted disease, and those with persistently elevated levels of the liver enzymes ALT and AST, despite low levels of HBV DNA. Based on Dr. Weisberg’s experience he has not found these risk factors to be entirely representative of his hepatitis delta patient population. The same study he conducted on hepatitis delta screening found that, by following the AASLD risk-based screening guidelines alone, about 18% of positive cases would have been missed. Of those positive cases, the patients tended to be younger and had significantly notable increase in liver disease progression and incidence of liver cancer. Dr. Weisberg encourages the testing of all hepatitis B-positive individuals to ensure the capture of all cases and linkage to appropriate care.

One major misconception among providers that Dr. Weisberg noted is that hepatitis delta is commonly referenced as a virus only seen in people living with HIV and people who use injection drugs (PWID). This translates to higher screening rates in those groups and leaves out a focus on those immigrant communities from highly endemic countries that can be very heavily affected by the virus.

Case Management Recommendations

Management of hepatitis delta patients requires a uniquely tailored approach for each case, but Dr. Weisberg outlined some of the general recommendations that he makes for his HDV+ patients. Since hepatitis D is so damaging to the liver, a main concern is keeping their liver as healthy as possible. This means reducing alcohol consumption to avoid developing alcohol-related liver disease and completing liver cancer surveillance (ongoing screening using non-invasive methods to detect early-stage hepatocellular carcinoma (HCC)). Dr. Weisberg recommends seeing your hepatologist once or twice a year and he personally checks patient labs and viral loads every six months, and transient elastography (FibroScans) every three years or so to check the stiffness and fat  changes in the liver. Other screening tools such as ultrasounds, alpha fetoprotein (AFP) markers, and Fibrosis-4 values are appropriate ways to stay updated on the liver health of all hepatitis delta-positive individuals. Most importantly, Dr. Weisberg stresses the need for a strong relationship between the hepatologist and the primary care provider in the long-term management of viral hepatitis patients, and a team-based approach with other providers in the clinical setting.

In terms of treatment options for hepatitis delta, the only currently available therapeutic is pegylated interferon alpha, which in Dr. Weisberg’s experience has not been effective in reducing his patients’ viral loads and tends to cause a lot of additional difficulties for his patients in their daily lives. He recommends careful consideration of which patients should be put on interferon treatment. In cases of contraindications such as diagnosis of autoimmune disease or severe risk of progressive disease, there is a possibility to appeal for compassionate use therapy for some treatments not yet fully approved in the United States. One such therapy is Hepcludex, the recently available treatment, which is presently only approved for prescription in Europe.

Finally, Dr. Weisberg’s management approach always involves the family of affected individuals, and discussions of how to keep transmission low for any who may be vulnerable to hepatitis B and D. One commonly cited reason for low delta screening rates for providers is “Why screen for people without a treatment?” Since hepatitis delta is highly transmissible, knowing one’s status allows the patient to be mindful about preventing exposure and infection of other household members, sexual partners, etc. Dr. Weisberg is a strong advocate for promoting hepatitis B vaccination in immigrant and adult populations (the vaccine also prevents hepatitis delta) and testing for the presence of hepatitis surface antibody (HbSAb) among close contacts of individuals living with hepatitis B and delta, to ensure low transmission rates.

The Promise of Future Treatments

“Every patient with [hepatitis] delta should be treated for [hepatitis] delta” but the major missing component is available treatments. Dr. Weisberg believes this to be the largest unmet need for his patients, but he emphasized hope for approval of treatments in the future. The availability of compassionate use therapy is a strong indicator for future approval since this was not always an option. Additionally, bulivertide (Hepcludex) is approved in the European Economic Area but is not yet approved by the Food and Drug Administration (FDA) in the United States. Dr. Weisberg explained that most information suggests that the delay in approval is more likely related to the need for reliable manufacturing and supply chain efficiency rather than a concern about the safety of the drug itself. (The FDA has not requested any further clinical trials, which is promising.) One common misconception in the provider community is that there will never be a cure for hepatitis B, but Dr. Weisberg remains confident in the progress being made towards both treatments for hepatitis D and a cure for hepatitis B.

Dr. Weisberg is one of many compassionate and knowledgeable physicians that manage people living with hepatitis B and D. If you need a provider, use our Physician Directory to find one near you!

References

European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on hepatitis delta virus. Journal of hepatology, 79(2), 433–460. https://doi.org/10.1016/j.jhep.2023.05.001

Nathani, R., Leibowitz, R., Giri, D., Villarroel, C., Salman, S., Sehmbhi, M., Yoon, B. H., Dinani, A., & Weisberg, I. (2023). The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection. Journal of viral hepatitis, 30(3), 195–200. https://doi.org/10.1111/jvh.13779

Terrault, N. A., Lok, A. S., McMahon, B. J., Chang, K., Hwang, J. P., Jonas, M. M., Brown, R. S., Bzowej, N., & Wong, J. B. (2018). Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 67(4), 1560–1599. https://doi.org/10.1002/hep.29800

World Health Organization: WHO. (2023, July 20). Hepatitis D. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d

Clinical Trials, HDV, Hepatitis D Drug Development, Hepatitis Delta (HDV), Liver, Liver Health, Research

Drug Profile: Three Hepatitis Delta Therapies That We Hope to See Widely Available Soon

 

 

 

 

The full extent of hepatitis delta’s (HDV) global disease burden is still unknown and treatment options for HDV have been limited. However, there are three promising up-and-coming drugs to treat HDV patients. This blog post details the drugs’ current phase of development and testing, how well they work for patients in the real world, and their current path toward regulation and market availability. 

Bulevirtide (Hepcludex) 

Gilead Sciences Inc. has been seeking approval from the U.S. Food and Drug Administration (FDA) for bulevirtide, or Hepcludex, since 2021. In 2020, Gilead acquired MYR, a German pharmaceutical company that had developed the hepatitis delta virus (HDV) drug. At the time that it was acquired, Hepcludex had already been conditionally authorized for use in Germany, France, and Austria (MYR Pharmaceuticals, 2020). Gilead, which is based in California, in the U.S., hoped to accelerate the global launch of Hepcludex. Since then, however, Hepcludex remains in regulatory limbo. In October 2022, the FDA announced the rejection of Hepcludex, citing concerns around the manufacturing and delivery of the drug. Gilead responded by stating that they plan to resubmit Hepcludex for approval as soon as possible (Dunleavy, 2022). Six months after the FDA rejection, the Committee for Medicinal Products for Human Use, which is the European Medicines Agency’s (EMA’s) committee responsible for conveying its opinions on medicinal products to the public, stated that it recommends Hepcludex for full marketing authorization in Europe. Since its conditional approval, a Phase 3 trial (which utilized data from patients in Germany, Italy, Russia, Sweden, and the U.S.) has shown it to be safe and effective for HDV patients. If the European Commission fully approves Hepcludex, it will be the only authorized HDV treatment available in Europe (Dunleavey, 2023).  

Lonafarnib 

At the end of 2022, Eiger Biopharmaceuticals announced that lonafarnib reached an important milestone in its phase 3 trial.  

The trial includes two regimens in patients with chronic HDV:  

  1. 1. Lonafarnib boosted with ritonavir, a protease inhibitor, which interferes with the ability of certain enzymes to break down proteins, often used in combination with other therapies for antiviral activity (this is an all-oral therapy), and
  2. 2. Lonafarnib in combination peginterferon alfa, an antiviral and immunosuppressive, which either completely or partially suppresses the immune system, often used to treat hepatitis B (HBV) and hepatitis C (HCV) patients (this is a combination therapy).

Both treatment arms showed statistical significance over the placebo arm of the trial. The placebo arm is used as a control in drug testing and has no therapeutic effect on patients. The results showed three noteworthy findings: 1. After 48 weeks (about 11 months) of treatment with the all-oral regimen, a small number of patients may achieve reduced viral load and improved liver function. 2. Combining lonafarnib and ritonavir with peginterferon alfa showed the potential to almost double the effectiveness of the drugs. 3. Combination treatment may lead to significant liver tissue improvement. Researchers found that most adverse symptoms related to treatment were either mild or moderate in severity, with gastrointestinal issues being the most frequent (Eiger Biopharmaceuticals, 2022). 

Peginterferon Lambda 

In June 2023, the results of a phase 2 trial looking at the safety and efficacy of peginterferon lambda (also an Eiger Biopharmaceuticals product) in HDV patients were published. Previously, peginterferon lambda showed a good tolerability profile (or the degree to which patients can tolerate negative treatment symptoms) in patients with HBV and HCV when compared to peginterferon alfa. In this trial, patients received 120-mcg or 180-mcg peginterferon lambda injections over 48 weeks, followed by 24 weeks of post-treatment follow-up. Researchers found that 180-mcg injections were more effective in HDV patients compared to the 120-mcg injections group. Results showed that with 48 weeks of 180 mcg treatment, patients showed a significant reduction in HDV RNA, the molecules responsible for perpetuating the virus in HDV patients. 36% of patients’ HDV RNA levels were undetectable. Some of the adverse symptoms patients experienced were flu-like symptoms and elevated transaminase levels, or enzymes that are related to a fatty liver. Most adverse symptoms were mild or moderate in nature and were resolved without additional treatment (Etzion et al, 2023). 

These three drug therapies show promise for HDV patients. Hepcludex is well on its way to becoming fully authorized in Europe after its three-year conditional approval and recent Phase 3 trial results. Lonafarnib’s phase 3 trial results are encouraging and Eiger, its manufacturer, plans to begin meeting with regulatory agencies, such as FDA and EMA, to discuss regulatory submissions (Eiger Biopharmaceuticals, 2022). Peginterferon lambda has shown a higher tolerability in patients with a lower adverse event rate than peginterferon alfa, which has been modestly used for the treatment of HDV over the past several decades (Etzion et al, 2023). Peginterferon lambda still has a ways to go before regulatory discussions, considering that results have just been published from its Phase 2 trial. Typically, in Phase 2 trials, researchers seek to learn whether the treatment they are studying is effective in fighting the disease. Phase 3 will test whether peginterferon lambda is more effective than already available, standard treatments. Hopefully, these three drugs continue to show positive results for HDV patients and will become widely available over the next few years. There are a number of other HDV drugs currently in development, but these are still in the early stages of clinical trial testing. You can stay up to date on the latest developments of these drugs by checking out the Hepatitis Delta Connect Drug Watch page. 

Dunleavy, K. (2022, October 28). Gilead hits surprise FDA rejection for hepatitis D drug already authorized in Europe for 2 Years. Fierce Pharma. https://www.fiercepharma.com/pharma/gilead-gets-fda-rejection-hepatitis-d-drug-already-authorized-europe-two-years 

Dunleavy, K. (2023, May 5). After FDA rejection, Gilead’s Hepcludex looks set for full EU NOD. Fierce Pharma. https://www.fiercepharma.com/pharma/gileads-hdv-drug-hepcludex-gets-thumbs-chmp 

Eiger announces both lonafarnib-based treatments in pivotal phase 3 D-LIVR trial in Hepatitis Delta virus (HDV) achieved statistical significance against Placebo in composite primary endpoint. Eiger BioPharmaceuticals. (n.d.). https://ir.eigerbio.com/news-releases/news-release-details/eiger-announces-both-lonafarnib-based-treatments-pivotal-phase-3 

Etzion, O., Hamid, S., Lurie, Y., Gane, E. J., Yardeni, D., Duehren, S., Bader, N., Nevo-Shor, A., Channa, S. M., Cotler, S. J., Mawani, M., Parkash, O., Dahari, H., Choong, I., & Glenn, J. S. (2023). Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial. Hepatology (Baltimore, Md.), 77(6), 2093–2103. https://doi.org/10.1097/HEP.0000000000000309  

MYR Pharmaceuticals. (2020, September 17). Myr Pharmaceuticals launches HEPCLUDEX® in Germany, France and Austria. PR Newswire: press release distribution, targeting, monitoring and marketing. https://www.prnewswire.com/news-releases/myr-pharmaceuticals-launches-hepcludex-in-germany-france-and-austria-301133006.html 

HDV, Hepatitis D Advocacy, Hepatitis Delta (HDV), Research

Why Is Hepatitis Delta So Hard to Eliminate?

Forty-five years after Mario Rizzetto discovered the hepatitis D virus (also known as HDV or hepatitis delta), scientists and advocates met for the first ever Delta Cure Meeting to discuss new scientific trends and global advocacy efforts to eliminate this difficult-to-treat disease. This conference included topics ranging from HDV’s global prevalence to new diagnostic methods, and the need for specific and improved efforts to fight this virus.

During the Delta Cure Meeting, scientists called for new global strategies to find people living with HDV and have prompted the World Health Organization (WHO) to update their screening guidelines to include HDV tests for all people living with hepatitis B (people who are HBsAg-positive). 

Unfortunately, some barriers continue to stand in the way of making this call to action a reality. Dr. Meg Doherty, the Director of Global HIV, Hepatitis, and STI Programmes at the WHO, stated in a recent Healio article that the WHO does not have any prevention recommendations that are specific to HDV. However, the WHO is developing updated guidance for HDV testing, diagnosis, and treatment as a part of hepatitis B (HBV)-focused elimination efforts.

While some initial progress has been made, (such as the inclusion of HDV in the 2022-2030 Global Health Sector strategies, which aim to increase knowledge about infections like HIV and viral hepatitis to create effective responses to and advance elimination efforts for these diseases), there is a need to expand elimination strategies to include HDV more broadly. The lack of robust inclusion of HDV disregards people who are currently living with HBV and are at the highest risk of HDV exposure and acquisition. People who have been diagnosed with HDV are overlooked as linkage to appropriate care, diagnostics and treatments (which are important for people living with HDV to stay healthy) continues to be out of reach for many. One of the major challenges with HDV is also the lack of testing and surveillance to identify those individuals living with delta and to understand the true burden of the disease. 

The WHO affirms that HDV elimination efforts must start with raising awareness of the virus and increasing advocacy efforts. The scientists at the Delta Cure Meeting are doing just that. Here are some solutions that scientists and researchers have identified to address the challenges surrounding HDV elimination:

Barrier: Overly complicated screening guidelines present a major barrier to the elimination of HDV. It was only in March 2023 that the Centers for Disease Control and Prevention (CDC) introduced new guidelines recommending universal HBV screening for all adults in the United States. A recommendation for universal HDV reflex testing (automatic testing for HDV when one tests positive for HBV) for all individuals living with HBV has still not been implemented in the US. Additionally, the American Association for the Study of Liver Diseases (AASLD) has screening guidelines for HDV that are still risk-based, meaning that only people who have certain risk factors are recommended to be tested for HDV (high-risk groups include people who inject drugs and men who have sex with men, among others). Conversely, the European Association for the Study of the Liver (EASL) and the Asian-Pacific Association for the Study of the Liver (APASL) have moved away from risk-based screening. Both EASL and APASL recommend that providers perform the HDV antibody total (anti-HDV total) test in all HBsAg-positive patients to identify whether someone has recovered from or is currently infected with delta antibodies (Palom et al., 2022; Hepatitis B Foundation, 2023).

Risk-based screening burdens both providers and patients alike. As part of risk-based testing, providers must ask questions about risk factors that are not necessarily part of a regular health screening and must know which factors indicate a need for HDV testing. Providers are often hesitant to ask their patients these questions, as talking about risk factors can be uncomfortable and overwhelming. But if providers do not ask, then the patient must know their own risk factors and ask for the test themselves (which can be very uncomfortable). A guideline to test everyone who is positive for hepatitis B (HBsAg-positive) for HDV would eliminate this confusion and hesitation. In light of this barrier, and the fact that risk-based testing is not evidence-based, the Hepatitis B Foundation recommends that all people living with HBV ask their doctors about getting tested for hepatitis delta.

Call to Action: Introduce new screening guidelines, including screening all adults who are HBsAg-positive for HDV. As the US does not have universal HDV screening guidelines, people who test positive for the hepatitis B surface antigen (HBsAg) but do not fall into a “high risk” category are not recommended to be screened for HDV, so they may be living with hepatitis delta and unaware of their infection. This puts these individuals at a much higher risk of having unmanaged hepatitis delta and developing liver cirrhosis or other advanced liver diseases at a more rapid pace. HBV is also already significantly underdiagnosed in the US and, as Dr. Nancy Reau neatly summarized “If you aren’t thinking about B, you’re not thinking about D.” 

Barrier: HDV is not a nationally notifiable or reportable condition in the United States. This means that healthcare providers are not required to report cases of HDV to local and state health departments or to the CDC. Because of this, the actual number of people living with HDV in the US remains underestimated, and without accurate prevalence data, prioritization of this neglected disease is made all the more difficult. 

Call to Action: Make HDV a reportable and notifiable disease in the US and beyond. Dr. Doherty of the WHO agrees that efforts to identify the populations most at risk for HDV are needed in the fight for HDV elimination, and specifically mentions the need for epidemiological surveys (different study designs of various sizes to better understand the burden of disease). A new survey method was discussed at the 2022 Delta Cure Meeting by Dr. Saeed Hamid in his presentation, “Epidemiology of HDV: From Low to High Endemic Countries.” Dr. Hamid called for new national surveys to be distributed to people with advanced liver disease because this population is one in which HDV is most likely to be found. He believes this monitoring method can be used in any country to advance elimination efforts.

Barrier: There are currently no standard HDV diagnosis methods, which makes HDV elimination very difficult to achieve. Professor Maurizia Brunetto, who presented “Diagnosis of HDV: Clinical Virology and New HBV Biomarkers,” explained that there is likely an underestimation of HDV infection in general, due to misdiagnosis (when someone is incorrectly diagnosed) and challenges accessing the diagnostic testing for hepatitis delta. When Dr. Doherty of the WHO was asked about what needs to be done to improve HDV elimination efforts (specifically in the US), she mentioned improving diagnostic testing tools.

Call to Action: Simplify testing and introduce point-of-care testing to increase HDV detection and diagnosis. Prof. Brunetto explained that point-of-care testing (getting rapid results within 20 minutes of being tested rather than waiting for up to 48 hours for results of a traditional blood test) can improve overall HDV diagnostics around the world. She believes it is especially important to introduce point-of-care testing in countries with less developed medical infrastructure. Having this point-of-care testing method will be easier to maintain and can identify people living with HDV earlier and link them to treatment before their disease becomes more severe. Dr. Stephen Urban, who led the discovery and creation of the first ever drug for HDV (bulevirtide), has been developing a point-of-care test to find delta antibodies from one single drop of blood. While only in the experimental phase, Dr. Urban and colleagues have published two journal articles that provide evidence for the test’s potential effectiveness in identifying people living with HDV (Lempp et al., 2021). While still more than two years away from using this method at a larger scale, Dr. Urban believes that this method can lead to faster HDV diagnostics.

As new HBV screening guidelines are introduced and new diagnostic tools are being developed, we have to advocate for universal HDV screening in individuals with hepatitis B by raising public awareness of the importance of screening and raising the voices of people who are living with HDV around the world. 

References

American Association for the Study of Liver Diseases [AASLD]. (2021, November). Hepatitis d (delta) at AASLD 2021.  https://www.natap.org/2021/AASLD/AASLD_136.htm 

Centers for Disease Control and Prevention [CDC]. (n.d.). Interpretation of hepatitis B serologic test results [Fact Sheet]. U.S. Department of Health & Human Services. https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf 

CDC. (2022). Nationally notifiable diseases. U.S. Department of Health & Human Services. https://www.cdc.gov/healthywater/statistics/surveillance/notifiable.html 

CDC. (2023, March 10). Screening and testing for hepatitis B virus infection: CDC recommendations — United States, 2023. MMWR | Recommendations and Reports, 72(1);1–25. https://www.cdc.gov/mmwr/volumes/72/rr/rr7201a1.htm?s_cid=rr7201a1_w 

Delta Cure. (2022, October). Program. https://www.deltacure2022.com/pages/program/index.php 

Delta Cure. (2022, October). Poster Exhibition. https://www.deltacure2022.com/pages/posterExhibition/index.php 

European Association for the Study of the Liver. (2017, April 17). EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. Journal of Hepatology, Clinical Practice Guidelines, 67(2), P370-398. DOI: https://doi.org/10.1016/j.jhep.2017.03.021

Hepatitis B Foundation [HBF]. (2023). Testing and diagnosis. https://www.hepb.org/research-and-programs/hepdeltaconnect/testing-and-diagnosis/ 

HBF (2023). Treatment. https://www.hepb.org/research-and-programs/hepdeltaconnect/treatment/ 

Lempp, F. A., Roggenbach, I., Nkongolo, S., Sakin, V., Schlund, F., Schnitzler, P., Wedemeyer, H., Le Gal, F., Gordien, E., Yurdaydin, C., & Urban, S. (2021). A Rapid point-of-care test for the serodiagnosis of hepatitis delta virus infection. Viruses, 13(12), 2371. https://doi.org/10.3390/v13122371 

Michael, E. (2022, October 31). Q&A: Expert discusses current state of hepatitis D, challenges in elimination efforts. Healio. https://www.healio.com/news/hepatology/20221031/qa-expert-discusses-current-state-of-hepatitis-d-challenges-in-elimination-efforts 

Palom, A., Rando-Segura, A., Vico, J., Pacin, B., Vargas, E., Barreira-Diaz, A., Rodriguez-Frias, F., Riveiro-Barciela, M., & Esteban, R. (2022, October). Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D. Journal of Hepatology, 4(10), 100547. https://doi.org/10.1016/j.jhepr.2022.100547 

Sarin, S. K., Kumar, M., Lau, G. K., Abbas, Z., Chan, H. L., Chen, C. J., Chen, D. S., Chen, H. L., Chen, P. J., Chien, R. N., Dokmeci, A. K., Gane, E., Hou, J. L., Jafri, W., Jia, J., Kim, J. H., Lai, C. L., Lee, H. C., Lim, S. G., Liu, C. J., … Kao, J. H. (2016). Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update. Hepatology International, 10(1), 1–98. https://doi.org/10.1007/s12072-015-9675-4

TheBMJ. (n.d.). Chapter 5. Planning and conducting a survey. https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/5-planning-and-conducting-survey

World Health Organization. (2022, July 18). Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022-2030. https://www.who.int/publications/i/item/9789240053779 

HDV, Hepatitis D Drug Development, Hepatitis Delta (HDV), Research

What You Need to Know About the 2022 Liver Meeting and How It Relates to Hepatitis Delta

 

 

 

 

This year, the annual Liver Meeting, hosted by the American Association for the Study of Liver Diseases (AASLD), was held in Washington, D.C. The featured presentations included new innovations in liver transplant surgery, disease modeling (which is a process that uses cells to show how a disease develops and to test possible treatment approaches), and drug development. While an effective, functional cure for hepatitis B virus (HBV) is still 5-10 years away, researchers, scientists, healthcare providers, and people with lived experience all came together and agreed that more needs to be done to reduce the burden of liver diseases and improve health outcomes now. One highlight of the meeting was Dr. Francis Collins, former director of the U.S. National Institutes of Health and special advisor to President Biden, hosting a special session to introduce a national hepatitis C elimination plan for the U.S. Unfortunately, this plan is focused on hepatitis C. As a response, the Hepatitis B Foundation will soon send an advocacy letter pushing for the inclusion of hepatitis B and hepatitis delta in this plan. Make sure you are signed up for our Action Center alerts to stay engaged with hepatitis B advocacy efforts.

Of particular note at this year’s meeting were the presence of many patient advocates and people with lived experience, and an increased focus on hepatitis delta. One important hepatitis delta poster presentation was delivered by Dr. Tatyana Kushner of Mount Sinai Hospital in New York City, entitled “HDV Patient Perspective: The Impact of Disease and Current Unmet Needs.” By including the perspectives of people living with hepatitis delta virus (HDV), this study aimed to empower the patient community. Dr. Kushner and her colleagues collected data on people’s quality of life to identify unmet needs, barriers and gaps in HDV care (including disease management and access-to-care inequities).

The researchers found that a person’s care is affected in two ways: In the care they receive for their clinical diagnosis and their emotional journey after diagnosis. The participants’ experience of care was often negatively impacted by having a delayed HDV diagnosis, and limited access to specialized care and tolerable treatment options. Findings describe that the lack of specific and acceptable treatment options for hepatitis delta left people with little hope, which put an emotional burden on their life post-diagnosis. Due to the gaps in providers’ knowledge of HDV, participants held little trust in their healthcare providers. The study participants also shared that they suffered emotionally due to the stigma attached to their diagnosis.

Dr. Kushner and her colleagues call for an increased effort to educate healthcare providers on hepatitis delta, as their lack of HDV-specific knowledge drives health disparities or differences between groups, where one group is more burdened by a disease than the other. These are driven by unequal opportunities to achieve good health (CDC, 2020). Health disparities are preventable, and educating providers is the first step to overcoming these inequalities. Educating providers on HDV will lead to more rapid identification of the disease, as they will have a better understanding of the signs, symptoms and risk factors for hepatitis delta. Increasing advocacy efforts for point-of-care testing for both HBV and HDV in the U.S. will increase levels of testing and earlier identification of people at risk for the diseases. Timely diagnosis allows for people to be linked to specialty care earlier, ultimately improving health outcomes. Improving community awareness of HDV will combat stigma and likely reduce testing hesitancy, which can improve health outcomes. The researchers call for drug developers to meet the needs of the patient community by developing tolerable and hepatitis delta-specific treatments.

In terms of drug development, researchers presented on antiviral treatments for people living with HDV and discussed preferred outcomes of treatment, based on what they believed to be most helpful to each individual’s physical health. To understand these treatment considerations, it is important to review how HDV functions. Hepatitis delta virus (HDV) uses a person’s RNA (ribonucleic acid) to produce and replicate the virus, so high HDV RNA levels in the blood indicate severe infection, and low or undetectable HDV RNA levels indicate that the virus is not rapidly reproducing (Stephenson-Tsoris & Casey, 2022). A virological response is defined as a long-term period of low-level replication that leads to undetectable HDV RNA levels in the blood six months after stopping treatment, and this indicates viral suppression (Yamashiro et al., 2004). A biochemical response is defined as normalization of alanine aminotransferase (ALT) levels after antiviral treatment (Kim et al., 2022). When liver cells are damaged, they release ALT into the bloodstream, so high levels of ALT indicate that one’s liver is diseased or damaged (MedlinePlus, n.d.). ALT normalization is considered a good indicator that antiviral therapy is working because it means that there is less liver damage, liver disease is less severe, and people living with HBV/HDV are at less risk of harm (Kim et al., 2022).

One study of interest from the meeting was the D-LIVR study by Eiger BioPharmaceuticals, Inc.: Lonafarnib Global Study in Chronic Hepatitis Delta. This study consisted of 400 participants, who were all on treatment for 48 weeks, then followed up with researchers 24 weeks after treatment. In total, 50 participants received pegylated interferon (Peg IFN) treatment for 48 weeks; 125 participants received a combination of Lonafarnib, Ritonavir and Peg IFN; and 175 participants received the oral antiviral therapy Lonafarnib and Ritonavir. There were also 50 people on a placebo treatment. A placebo is a harmless pill that has no effect on a person, and is often used in clinical trials to test the effectiveness of a specific treatment being studied, in this case, Peg IFN, Lonafarnib and Ritonavir (Harvard Health Publishing, 2021). The researchers decided that they wanted to see a decline in HDV RNA (virologic response) and normalization of ALT (biochemical response) at week 48 as their study’s main outcome or proof that the treatment could work. In this study, an acceptable virologic response was defined as a “2log decline of HDV RNA levels,” which means they wanted to see HDV RNA levels decrease by 99% from the original levels that were measured before starting treatment (Wikipedia, n.d.).

Pegylated interferon (Peg IFN) is a protein-based medication that prompts the body to activate its natural immune system (induce innate antiviral response) (Zhang & Urban, 2021; Drugbank, n.d.). For Peg IFN-based treatments, researchers determine that undetectable HDV RNA six months after stopping treatment is desirable. However, researchers emphasize the importance of yearly HDV RNA post-treatment screening to monitor for viral relapses after treatment. For long-term treatment (over 48 weeks), a 99% reduction of HDV RNA concentration levels is an appropriate virologic response for non-interferon-based treatments, but more studies must be done to establish whether a person living with hepatitis delta is actually benefiting from the treatment (this is called clinical benefit). When establishing the clinical benefits for non-interferon-based treatments (or any new treatment), researchers can measure delays in disease progression or improvement of signs and symptoms of the disease, which includes symptom relief, improved functioning and improved survival rates (Lee, n.d).

Based on a variety of extensive studies (not just D-LIVR), the researchers decided to combine virologic and biochemical responses to try to demonstrate the clinical benefit of using ongoing antiviral treatment as a functional cure for hepatitis delta. They concluded that acceptable endpoints for HDV treatment studies include undetectable HDV RNA six months after stopping treatment, the loss of the hepatitis B surface antigen (HBsAg), and ALT normalization in people living with chronic hepatitis delta. This can also be considered a functional cure since there are undetectable levels of HBsAg and HDV RNA in the blood for a sustained period of time, even after finishing treatment (Wong et al., 2022).

While there is still time before we overcome the burden of hepatitis delta, the presentations from The Liver Meeting show us that researchers and scientists are constantly working to improve the lives of people living with hepatitis delta. Development toward a functional cure is progressing, and advocates are incorporating peoples’ lived experiences and perspectives into drug development and education. Collaboration between all these groups is the best way to move forward in the fight against hepatitis delta.

For more information on hepatitis delta, you can visit the Hepatitis Delta Connect website or review this hepatitis delta fact sheet.

References

Centers for Disease Control and Prevention. (2020). Health disparities. Centers for Disease Control and Prevention, Division of Adolescent and School Health, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. https://www.cdc.gov/healthyyouth/disparities/index.htm 

Drugbank. (n.d.). Peginterferon alfa-2a. Drugbank. https://go.drugbank.com/drugs/DB00008

Harvard Health Publishing. (2021, December 13). The power of the placebo effect. Harvard Health Publishing, Harvard Medical School. https://www.health.harvard.edu/mental-health/the-power-of-the-placebo-effect 

Kau, A., Vermehren, J., & Sarrazin, C. (2008). Treatment predictors of a sustained virologic response in hepatitis B and C. Journal of Hepatology, 49(4), 634-651. https://doi.org/10.1016/j.jhep.2008.07.013

Kim, S. H., Cho, E. J., Jang, B. O., Lee, K., Choi, J. K., Choi, G. H., Lee, J. H., Yu, S. J., Kim, Y. J., Lee, Y. B., Yoon, J. H., Kim, J. W., Jeong, S. H., & Jang, E. S. (2022). Comparison of biochemical response during antiviral treatment in patients with chronic hepatitis B infection. Liver International: Official Journal of the International Association for the Study of the Liver, 42(2), 320–329. https://doi.org/10.1111/liv.15086 

Lee, J. (n.d.). Defining Clinical Benefit in Clinical Trials: FDA Perspective [Presentation]. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. https://celiac.org/main/wp-content/uploads/2015/04/great3-07.pdf 

MedlinePlus. (n.d.). ALT blood test. National Library of Medicine (U.S.). [updated August 3, 2022]. https://medlineplus.gov/lab-tests/alt-blood-test/ 

Raman, S. (2022 October 25). Administration eyes national hepatitis C treatment plan. Roll Call: Policy. https://rollcall.com/2022/10/25/administration-eyes-national-hepatitis-c-treatment-plan/ 

Stephenson-Tsoris, S., & Casey, J. L. (2022). Hepatitis delta virus genome RNA synthesis initiates at position 1646 with a nontemplated guanosine. Journal of Virology, 96(4), e0201721. https://doi.org/10.1128/JVI.02017-21 

Wikipedia. (n.d). Log reduction. https://en.wikipedia.org/wiki/Log_reduction

Wong, G. L. H., Gane, E., & Lok, A. S. F. (2022). How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?. Journal of Hepatology, 76(6), 1249–1262. https://doi.org/10.1016/j.jhep.2021.11.024

Yamashiro, T., Nagayama, K., Enomoto, N., Watanabe, H., Miyagi, T., Nakasone, H., Sakugawa, H., & Watanabe, M. (2004). Quantitation of the level of hepatitis Delta virus RNA in serum, by real-time polymerase chain reaction—and its possible correlation with the clinical stage of liver disease. The Journal of Infectious Diseases, 189(7), 1151–1157. https://doi.org/10.1086/382133

Zhang, Z., & Urban, S. (2021). New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. Journal of Hepatology, 74(3), P686-699. https://doi.org/10.1016/j.jhep.2020.11.032

HBV, HDV, Hepatitis B Treatment, Hepatitis Delta (HDV), Liver, Liver Health, Living with Hepatitis B

What’s the Difference?: Herbal Remedies and Supplements vs. Western Medicine

What’s the Difference?: Herbal Remedies and Supplements vs. Western Medicine

Around the world, people consider the use of herbal remedies or supplements as a natural treatment for hepatitis B and/or D infection. These natural remedies have historically been advertised to boost the immune system and improve liver health. Herbal remedies or supplements are described as products made from botanicals or plants used to treat diseases and maintain health. They can be produced in a variety of forms including liquid extracts, teas, tablets/capsules, bath salts, oils, and ointments4.

Why do people choose to use herbal remedies?

The use of these products over time has social-cultural influences related to the distrust of and unfamiliarity with western medicine for management of hepatitis B or D infection. While herbal remedies have been used widely across cultures and contexts, patterns of racism, medical mistreatment, and inadequate delivery of care in western medicine have influenced the present state of treatment practices. In response to these barriers to sensitive and effective health care delivery, many groups such as Hmong and African communities often rely on herbal remedies and supplements to treat medical conditions and ease suffering.

Silymarin, milk thistle, and Kampo medicine

The distrust of western medicine has contributed to more widespread use of supplements such as silymarin (milk thistle) and Kampo medicine, as alternatives to manage hepatitis B or D infection. Many people believe that Silymarin can improve liver health through its antioxidant and free radical-fighting properties. Traditional Kampo medicine has been used for over 2,000 years to treat a variety of diseases including hepatitis B. One herbal treatment that is frequently used is bupleurum which many people believe can protect the liver or heal liver damage. Despite possible liver health benefits, neither supplement is a treatment for hepatitis B or D and may sometimes cause further harm to the liver4. It is important to note that there is presently no cure for hepatitis B.

False claims and bad interactions

Additionally, several alternative medicine companies often make false claims and testimonials to convince people to purchase expensive alternative treatments with false promises that are not based on scientific evidence. Herbal remedies and supplements may also interact with certain medications prescribed for those with hepatitis B and D, so it is important to seek the advice of a health care professional before use of any of these products3,4.

Strides in western health care

The long-standing hesitancy to participate in western health care is well-reasoned and firmly rooted in past wrongdoing on the part of often fundamentally racist institutions. While the western health care system remains far from perfect, it is important to remember that many strides continue to be made to correct the misdeeds of the past, and conversations around health equity and the social determinants of health (including racism) are becoming more and more common. Meanwhile, research has found that beliefs and misconceptions around western medicine can delay care and increase morbidity rates of hepatitis B in high-risk communities2.

It is vital for those living with hepatitis B or D to stay informed with scientific knowledge about supplements and herbal treatments to ensure these products are effective and safe in their daily life. The coordination of hepatitis B and D care by providers must do better to support those impacted by the viruses, in a way that is culturally sensitive and not dismissive of the harm that has been inflicted on communities of color and immigrant communities, who are more likely to be affected by hepatitis B and D1.  Health care professionals and other service providers must continually work to improve their cultural humility. In addition, health care institutions practicing western medicine must work harder to ensure care is equitable and safe, and to center the voices, stories, and insights of community members in their work to repair the impacts of structural racism and medical mistreatment that have caused such deep distrust in western medical treatments.

To learn more about effective hepatitis B and D medications, check out our Drug Watch page!

Disclaimer: Herbal products are not U.S. FDA-approved, and the Hepatitis B Foundation cannot endorse the usage of such products that lack regulation and scientific evidence to deem them both effective and safe.

References

  1. El-Serag, H., McGlynn, K. A., Graham, G. N., So, S., Howell, C. D., Fang, T., … & Thiel, T. K. (2010). Achieving health equity to eliminate racial, ethnic, and socioeconomic disparities in HBV-and HCV-associated liver disease. The Journal of Family Practice, 59(4 Suppl), S37.
  2. Mukhtar, N. A., Evon, D. M., Yim, C., Lok, A. S., Lisha, N., Lisker-Melman, M., … & Khalili, M. (2021). Patient knowledge, beliefs and barriers to hepatitis B Care: results of a multicenter, multiethnic patient survey. Digestive diseases and sciences, 66(2), 434-441.
  3. National Center for Complementary and Integrative Health website. Using dietary supplements wisely. (2019). Using dietary supplements wisely. https://www.nccih.nih.gov/health/using-dietary-supplements-wisely.
  4. US Food and Drug Administration. (2017). Information for consumers on using dietary supplements. https://www.fda.gov/food/dietary-supplements/information-consumers-using-dietary-supplements.

Clinical Trials, HDV, Hepatitis D Drug Development, Hepatitis Delta (HDV), News, Research

Results from Hepatitis Delta Clinical Trials Announced at International Liver Congress 2022

London, UK was the host city for this year’s annual International Liver Congress (ILC), the yearly meeting of the European Association for the Study of the Liver (EASL), which took place from June 22nd-26th. This meeting provides an opportunity for those working to address liver diseases around the world to gather in one location and exchange ideas, present research, and work to advance diagnosis, prevention, treatment, and elimination of these serious conditions. This year’s meeting saw significant attention given to hepatitis delta, as new treatments continue to move through the pipeline and more widespread approval for prescription of current treatments is sought. Below is a quick snapshot of some of the presentations!

The US-based pharmaceutical company Gilead Sciences, Inc. demonstrated with results from a Phase 3 clinical trial that treatment with Hepcludex (bulevirtide), the first medication ever approved for hepatitis delta (HDV), has been shown to achieve significant response in chronic HDV. After 48 weeks, 48% of study participants who received different doses of treatment with Hepcludex achieved virological response (meaning a decline in hepatitis delta viral load, ALT normalization, and a change in liver stiffness), compared to only 2% of those who had not received any treatment. When compared to results from clinical trials after 24 weeks, response rates to HDV only improved, showing the drug to be even more effective over time. Throughout the clinical trials, there have been no adverse events reported that are attributable to this treatment.

Hepcludex has also been found to have a positive impact on the quality of life of individuals living with hepatitis delta, and their overall ability to manage the condition. There were improvements found in health distress, performance of daily activities related to hepatitis, emotional impact of hepatitis, and ability to work. This data reinforces the efficacy and safety of Hepcludex and hopefully strengthens the case for approving the drug in more parts of the world.

“As the most severe form of viral hepatitis, HDV presents a significant disease burden with high healthcare-related costs and until recently, no approved treatment options,” said Heiner Wedemeyer, MD, Director, Clinic for Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, and principal investigator of the study. “These results presented at ILC 2022 not only highlight the important clinical role that bulevirtide has to play as a safe and effective treatment option for chronic HDV, but critically also demonstrate that with prolonged treatment, we can achieve higher response rates so we can better manage this rare, life-threatening disease in more people.”

Presently, Hepcludex has been conditionally approved by the European Commission for prescription in France, Germany, and Austria. It has not yet been approved by the United States Food and Drug Administration (FDA) or in other countries. A Biologics License Application was submitted by Gilead to the FDA in late 2021 for injection of 2mg of Hepcludex to treat adults with HDV and compensated liver disease. Hepcludex had previously been granted Breakthrough Therapy and Orphan Drug designations by the FDA and PRIority MEdicines (PRIME) scheme eligibility by the European Medicines Agency (EMA).

The second company to present their research findings at the ILC was US-based Eiger BioPharmaceuticals, Inc. The two primary hepatitis delta drugs that they have in the pipeline are called lonafarnib and peginterferon lambda. One abstract presentation indicated that peginterferon lambda (lambda) had better antiviral activity and tolerability than peginterferon alfa (the previous version of this drug that has been used as the only somewhat effective, but off-label treatment for hepatitis delta since the early 1980s). Lambda has been shown to block production of new hepatitis delta virus very effectively. Additionally, lambda in combination with lonafarnib was found to lower levels of HDV RNA and decrease its production and release, more effectively than lambda by itself. Patterns in HBV DNA, hepatitis B surface antigen, and ALT were also observed as part of this study. In its Phase 3 D-LIVR study, which is assessing the safety and efficacy of lonafarnib in combination with ritonavir, with and without peginterferon alfa, Eiger has assembled the largest cohort of global participants in an HDV study, and therefore the largest body of data. Results from this study are anticipated by the end of 2022.

The final piece of big hepatitis delta news to come out of the conference was the announcement from Vir Biotechnology Inc. that they are beginning a Phase 2 clinical trial for VIR-2218 in combination with VIR-3434 for the treatment of chronic hepatitis delta. Initial data from this study is anticipated in 2023.

Hepatitis delta is now receiving more attention than ever before and there is only more hope as new treatments are created, investigated, approved, and made available. For a complete overview of hepatitis delta, including basic information, resources, clinical trial opportunities, and a complete list of drugs that are in the pipeline, visit www.hepdconnect.org.

References

https://www.gilead.com/news-and-press/press-room/press-releases/2022/6/treatment-with-hepcludex-bulevirtide-meets-primary-endpoint-and-achieves-significant-response-in-chronic-hepatitis-delta-virus-at-48-weeks

https://www.streetinsider.com/Corporate+News/Vir+Biotechnology+Inc.+%28VIR%29+Announces+New+Clinical+Data+From+its+Broad+Hepatitis+B+Program/20256465.html

https://www.prnewswire.com/news-releases/eiger-biopharmaceuticals-announces-results-from-multiple-presentations-at-the-european-association-for-the-study-of-the-liver-easl-international-liver-congress-2022-301576119.html

HDV, Hepatitis D Advocacy, Hepatitis Delta (HDV)

Recent Roundtable Discussion Highlights Hepatitis Delta Virus

April 21st and 22nd, 2022 marked the occurrence of a roundtable meeting solely focused on hepatitis delta virus (HDV), which was jointly hosted by the American Liver Foundation and the Hepatitis B Foundation. This was one in a series of events taking place this year to raise the profile of hepatitis delta, a serious coinfection of hepatitis B virus (HBV) that is estimated to affect between 5 and 10% of people who are living with HBV. HDV is more severe than HBV alone, with a 70% chance of developing into cirrhosis or liver cancer if unmanaged, compared to an approximately 25% chance for those living with HBV alone. With approval of the first official treatment for hepatitis delta in Europe in July of 2020, expected approval in the United States later in 2022, and other treatments moving through the clinical trial pipeline, more is happening in the world of hepatitis delta than ever before. Despite the promising treatment landscape, the virus still remains significantly under-diagnosed (making estimation of true prevalence difficult), largely due to lack of awareness, low prioritization compared to other health conditions, and limited advocacy, and big questions persist about treatment equity, including access to knowledgeable providers, clinical trials, and available medications. The purpose of this roundtable was to begin a conversation among a diverse group of stakeholders about some of these issues, to bring attention to HDV and its potential consequences, to identify unmet needs in this area, and to prepare calls to action and next steps to address these needs.

Participants at the roundtable included individuals living with hepatitis delta, caregivers, healthcare providers, public health professionals, and representatives from community-based organizations. The conversation was very generative and really underscored some of the key issues that exist around hepatitis delta, including gaps in awareness and knowledge among medical and high-risk communities and limited access to and availability of HDV screening and care. These factors lead to under-diagnosis and under-surveillance, making the production of accurate data difficult, which in turn complicates advocacy efforts, since compelling data is often a key ingredient for policy change that might make screening, treatment, and linkage to care more available and accessible.

The ultimate planned outcome of this virtual event will be production of a white paper that will highlight key takeaways from the discussion, clearly outline unmet needs and priority issues for people living with HDV, and detail calls to action for stakeholders at every level to meet these needs and overcome some of the significant barriers and challenges that persist in diagnosing, managing, and treating HDV.

Another goal of the meeting was to begin to develop resources that can better support and engage the larger community around HDV awareness and advocacy – a first step toward this goal will be creation and dissemination of a visually appealing infographic, which will provide at-a-glance information about HDV and its estimated prevalence, transmission, prevention, testing, and treatment.

The white paper and infographic are expected to be complete by early summer 2022. The organizers of this roundtable meeting are hopeful that its outcomes will bring hepatitis delta virus more into focus for various stakeholder communities and generate more engagement and energy around this dangerous virus that has long been neglected and is not receiving the attention it deserves.

Baruch S. Blumberg Institute