Hepatitis is an inflammatory disease that affects the liver. Certain types can lead to liver cancer or even death. According to the World Health Organization (WHO), about 325 million people globally live with a hepatitis infection. To highlight the missing gaps in our understanding of hepatitis, and to bring more awareness to this year’s World Hepatitis Day, we spoke with Neddie Zadeikis, Medical Director, Medical Affairs Therapeutic Expertise, and Tristan Baldwinson, Director of Project Delivery, Project Management. Below they share their insights.
What types of hepatitis are there? How are they different?
When we speak of hepatitis, which basically means inflammation of the liver, we usually are referring to viral hepatitis. Although there are many viruses that can cause hepatitis, the ones that we focus on are hepatitis A, B, C, D, and E. Hepatitis A and E are spread by contaminated food and water, so essentially a fecal-oral route of transmission, while hepatitis B, C, and D are typically spread through contact with body fluids, such as during sexual contact or through sharing of contaminated needles. Viral hepatitis can affect anyone of any age. The development of the hepatitis depends on the exposure.
The challenge of diagnosing hepatitis is that many cases are asymptomatic in early stages of the disease. In some cases, patients with a chronic viral hepatitis can be identified through screening for another illness or procedure (ie, blood donation). Typically, something triggers a higher index of suspicion—for example, you may see laboratory abnormalities in the liver chemistries, which could give you a hint that someone has viral hepatitis.
There may also be other non-specific symptoms, which, when taken into context of other lab findings, may indicate an issue with the liver that requires further tests. For example, patients may present with fatigue, nausea, or fever. With hepatitis A and E, you can have diarrhea. As the disease progresses, patients could also present with yellowing of the skin or the whites of the eyes (jaundice), so you need to be on the lookout for both asymptomatic cases as well as those who present symptoms.
Who does hepatitis affect, and where?
Hepatitis A and E are more commonly seen in developing countries, where a clean water and food supply may not be possible in rural areas. Hepatitis B, C and D are seen worldwide, where it's more spread through sexual contact, sharing needles, or any other blood and body fluid contact.
One thing that has positively impacted the incidence rate of hepatitis B is the availability of a vaccine. In many countries, it’s universally administered to newborns. Still, half the countries in the world don’t administer the vaccine for health policy or financial reasons. Those are the countries, mostly in Asia and sub-Saharan Africa, are where you commonly see hepatitis B.
A big part of the vaccination effort came from the recommendation of the WHO in the 80s. Many incidence rates declined globally as a result, but as Neddie mentioned, it wasn’t implemented at the same time nor with the same rigor globally. That means there are still areas of high prevalence and incidence that affect millions of people.
More recently, this pattern has been affected with geo-political factors, too—if you take conflicts like those in the Middle East, for example, which has created millions of refugees in an area with higher prevalence of hepatitis B, we’re starting to see increases in diagnosis from countries supporting the humanitarian effort.
Here in the UK, we scaled back on vaccination efforts for hepatitis B—only vaccinating more vulnerable or high-risk populations, such as those in front-line medical services. However, in 2017, hepatitis B was reintroduced as part of the newborn vaccination program.
Hepatitis B tends to be a lot more prevalent in Asia and sub Saharan Africa currently likely due to lack of infant immunization. A child born to an infected mother who gets hepatitis B will have a 90% chance of the infection becoming chronic. In regions where there is much immigration, travel, or migration, you tend to also have a higher prevalence—we see this, for example, in places like Asian communities in the east and west coast of the US.
Many people live with hepatitis and are unaware of the disease. Why is that? How could we make them aware?
One thing to note is that hepatitis A and E are just acute infections that people get over. They typically don’t involve chronic infections. It's hepatitis B, C, and D that can become chronic infections. These lead to deterioration of liver functions over the years, ultimately leading to liver cirrhosis and failure. That means patients may need a liver transplant, or they develop liver cancer and die. Hepatitis B, C, and D are the most important to focus on because of the chronicity.
I think part of that challenge is making sure there's no gaps in the system. There are guidelines that recommend that the below groups of people with risk factors get tested for hepatitis B and C:
- People who are sexually active with more than one partner in the last six months
- Men who have sex with men (MSM)
- Intravenous drug users
- Household contacts of people who are chronically infected with these viruses
- Healthcare professionals who can have exposure to blood and body fluids, etc.
Testing is an important part but getting people to test is also a challenge. Not everyone has access to the healthcare system on any sort of regular basis, so the majority of people will probably see their physician once a year for a checkup.
Still, there’s huge numbers of people who don't have that luxury. They only go to the doctor when they're actually ill.
The next challenge is getting the results back to the patient. People can fall through the cracks because there may not be follow-up with the patient to let them know what the results are. It may be due to a telephone number change, a move out of the area, or something in the infrastructure of the health care system that causes people to fall through the cracks.
Even if someone is aware of their results, they may not understand the significance of them. They may believe that if they feel fine, they don't need to do anything about it, unless there's been good education at the site of what a positive test actually means. Some people may not take advantage of the treatments that are available.
Bridging each one of these gaps is important if we're going to impact the number of cases of hepatitis B and C and/or impact the people who are infected.
What treatments currently exist for Hepatitis B, C, and D?
For hepatitis B, there are four treatments currently available. Three of them are anti-viral agents that work to block the viral replication and there’s also a pegylated interferon product, which can also be used to provide the bodies innate antiviral response. All of these treatments are challenging because they can decrease the amount of circulating virus in the bloodstream, but they can’t actually clear the liver of the virus. They’re all just a temporary measure to keep the viral replication in the bloodstream in check. Unfortunately, there is no cure yet for hepatitis B.
For hepatitis C, there are five primary medications available that actually cure 95% of people in treatments that run anywhere from 8-12 weeks. Unlike the hepatitis B treatments that are generic, these are all branded drugs. Hepatitis C has seen great strides in research and tremendous success for treatments and cures.
Hepatitis D is interesting because you cannot get hepatitis D by itself. You can only receive it in two ways: at the same time as hepatitis B, or from a secondary exposure to hepatitis D sometime after the original hepatitis B infection. So, if you’re coinfected with hepatitis B and D, you can receive treatment for hepatitis B, but not hepatitis D, as there are no treatments or cures yet. This all links back to getting people vaccinated for hepatitis B so they don’t present with D as well.
I think disease awareness and education is key, particularly from an outreach standpoint. When we think in laymen’s terms, many of us will understand that viral hepatitis affects the liver, but what you don’t perhaps appreciate right away is the difference between the viruses that can use hepatitis as it relates to the route of transmission, disease progression, and cure vs. lifelong infection.
Though all hepatitis viruses are related phylogenetically, the way they infect the hepatocytes (the cells of the liver) are different.
These differences are why with hepatitis C, for example, we were able to not only treat and control the virus, but to go on to develop a cure that’s effective in >95% of people infected.
Hepatitis B is a different beast. In terms of its mechanism of action, it’s more akin to something like HIV—the virus that can cause AIDS. It uses its genetic material and the host cell apparatus to replicate, like any other virus, but it’s also able to “hide” within the nucleus of the host cell, making it a difficult target for therapeutics. At that point, it's difficult to eradicate.
So, all medications given for hepatitis B are essentially just treatments. It’s possible to see a functional cure in some people, but a very low percentage of patients achieve this. Most medical treatments available today, much like those used to treat HIV, are aimed at stopping the virus replicating, as replication would cause cell death, fibrosis, and other issues down the road.
Unfortunately, all of that never truly gets rid of the virus. Certain stages of life, or certain inflictions that you have—maybe immunotherapies for oncology, for example—can cause a resurgence of the virus, which makes your risk levels increase.
To most people, when they think of hepatitis, they just think it's all under one umbrella. But it's different in terms of prognosis and how it’s treated.
Have either of you heard of any research that's going into cures for hepatitis B?
If you look at the industry activity over last ten years or so, it focused a lot on hepatitis C. It was a big medical need based on the poor prognosis for patients with hepatitis C and the burden to the healthcare systems worldwide through liver transplantation and/or liver cancer as a result of the infection. But now that you have curative drugs that are available to patients, many pharmaceutical companies’ attentions toward hepatitis split off into two areas, as other causes of transplant and liver cancer overtake those seen from hepatitis C.
The first area is fatty liver diseases, like non-alcoholic steatohepatitis and nonalcoholic fatty liver disease (NASH). These are linked to metabolic or cardiovascular diseases like hypertension, diabetes, hyperlipidemia, and obesity. The second area is hepatitis B. Even relatively recently, pharmaceutical companies started to identify more of the molecular targets for hepatitis B. I think what that's done is focus attention on the potential drugs that might target those mechanisms.
The industry has effective treatments for hepatitis B such as antiviral agents. Using these antivirals as a backbone, we’re trying further to get to the elusive reservoir of the virus that hides within the host cell. Research is attempting to stop not only the replication of the virus to stop infection of other neighboring cells, but to look at ways to create a cure.
For example, triggering the immune system (which is somewhat typically damped in the liver and “ignores the virus”) generates an innate response to target and eradicate infected cells.
What is currently being done to raise hepatitis awareness and address the stigmas associated with hepatitis? Are there any organizations or campaigns you’ve heard about?
One avenue certainly involves awareness, but another important piece is for patients is addressing stigma surrounding hepatitis.
My colleague, Dr. Jovana Burilovska, PRA medical director, infection disease physician, and former advisor to the Ministry of Health in Macedonia, can speak to a lot of the stigma around hepatitis:
“Chronic illnesses are inevitably are tied to stigma, which is an unspoken part of the psychological burden that the patients carry around. This is especially true with chronic infectious diseases, because the stigma is yet more associated with the taboos of sex and drugs and all they represent for a specific nation, group of people and even the individual,” says Dr. Burilovska. “Hepatitis B has very little to do with sex and drugs, as the chronic form is an infection usually acquired in childhood (mostly perinatally), or via some form of treatment (at least in the past) as dental or surgical interventions.”
In her personal experience working 24-hour shifts, she would spend time in the department of viral hepatitis in the clinic. She would sit in a circle in the hallway of the clinic, where her patients were eager to ask questions, to share their fears, to be calmed and reassured. She says, “I always tried to make them realize that, despite the way they contracted the diseases, it’s something that they have to learn to live with as much as possible that the disease is not some sort of punishment, that they will not be judged by it. I just wish that more colleagues would do that, because these sorts of discussions actually had an effect of the improvement of their symptoms and wellbeing.”
What you find is that many people feel lost with what this disease means for them—a hopelessness of a lack of cure. In many cases, they were ashamed or worried about what their diagnosis might mean for the way others viewed them or interacted with them once they knew. Some physicians we work with also report that patients are reluctant to seek treatment for the disease because of this stigma, so we have to do more to educate and to help patients with the psychological aspects of chronic diseases like this.
I think education is important not only for those dealing with the disease, but for those around them to dispel misconceptions, judgements, and stigma. There’s great information and organizations available for patients, caregivers, or those just interested to learn more.
The WHO, for example, has a lot of information on viral hepatitis on their website, as well as those dedicated to the diseases. Below is a list of other helpful resources:
There are organizations like the American Liver Foundation that help spread useful information about hepatitis. I’ve also heard of many worldwide support groups for both hepatitis and liver disease in general. They keep abreast of research and educate individuals as to potential clinical trials for them to participate in or other means to get treatment for chronic liver disease.
Those are all good conduits for spreading the word about different trials. They’re available to educate individuals on the diseases and what treatment options may be available.
Integrated Drug Development
Ask the Experts: What Does the World Need to Know About TB?
According to the World Health Organization, Tuberculosis (TB) is the world’s leading infectious cause of death. Despite significant advances in…