From the Vault - Hepatitis B: Hepatiti, Take 2 (Ep 89)

This is exactly right. People who didn't do what John F. Quad wanted them to do, they usually disappeared. John of God was once Brazil's most famous spiritual healer. But in this limited series podcast, we uncover the darker truth behind his global empire of faith and fear. From exactly right and a Donde media, this is Too Faced, John of God. Listen on the iHeart Radio app, Apple podcasts, or wherever you get your podcasts. My name is Siu Wang. I am a physician. I'm an MD and pH on the medical director for the Center for Asian Health and viral hepatitis programs at the Cooperman Barnabas Medical Center. I'm also just coming off to your presidency for the World Hepatitis Alliance, which is a nonprofit organization that represents patients living with viral hepatitis. And our goal is to harness the power of people living with viral hepatitis to achieve global elimination of viral hepatitis. I was diagnosed with hepatitis B in college. In my first year of college, I went to donate blood to do a good thing, donate blood, and shortly after I got a big fat envelope sent to my dorm and it said, don't be worried. You don't have HIV, but you do have hepatitis B. And I was a pre-med student, but honestly, I didn't know anything about happy. I called my sister, confided in her about the new diagnosis and she said, oh, didn't you know mom also has happy. And then I just, I just remember thinking, oh, who do I need to tell? And when I went back home, I did go see a doctor and talked to her about it. And I think she did blood work and basically said I was a carrier and there was nothing to worry about. So I honestly pushed it to the, you know, back burner, didn't want to think about it. So it didn't come up again until med school. I filled in all my med school forms and a lot of our employment forms and our screenings for working at a hospital. You do have to indicate, you know, what your happy vaccination and statuses and I had indicated that I was a carrier and didn't hear anything about it. I didn't think anything up and it's not till now that I've heard numerous people who are in med school found out to have happy and actually they lose their acceptance is to med school. And so I was like, well, I'm not sure if I could have been a carrier or they faced quite a bit of what I would consider discrimination over their status. And it's happened to residents, it's happened to nurses, it's happened to dental students. So it is an issue of stigma and discrimination. But I was fortunate it didn't happen to me. And kind of was in the back of my mind and I remember kind of when we learned about hepatitis, just kind of listening a little bit more tentatively. And after med school, I became really good friends with somebody a friend of mine went into infectious disease and I had confided in her that I had hepatitis B and she told me, oh, make sure you see a doctor for a hand seen a doctor in years at that point. So I went in to see somebody and they did my viral load and I did the ultrasound and everything was fine. It was very low. I didn't need medication. And at that point, I remember I was engaged, I think. And so my friend had said, oh, make sure your fiance also gets tested and he ended up getting tested and needing to get vaccinated. And so that was kind of the extent of how it impacted my life. And I had told him about it. And I was, you know, I was happy that he was, he didn't make a big deal out of it. These are all points now looking back, I realized, you know, I was fortunate and so many people around the world are not so fortunate to have, you know, a career that's not affected by it or a relationship that's not affected by it. You know, there are a lot of people who, you know, lose their partners, they end up, they may get divorced, they may get disowned by family or unable to pursue the career they went to. So I didn't have any of that. And I got married and we got pregnant. I've had four kids and with each one of those kids, especially the first one, it did hit me that, oh, I know, there's a chance that I could pass this affection on to my children. And that definitely weighed heavily on me, although I knew the research that because my viral load was low, there would be very low chance of the infant developing heartbeat. But that's where I really all of a sudden felt like, oh, my gosh, you know, this could really impact me personally. And I'm happy to say that all for my kids are happy free. And that they don't have to live with this chronic disease and worry about risk of liver cancer and other things that other kids have to go through, even now in the stage. And so as a physician, I, I didn't particularly have a inkling that I was going to do hepatitis work at all. And it wasn't until I moved to New York City after I finished my residency and I took a job with a community health center in Chinatown. So I began serving the largely Chinese community in Chinatown and learned so much more about that, that I ever knew that it's, you know, one of the most common infectious diseases around the world up to like one in 10 of our patients had had be as common as a hypertension. And whereas I had seen specialists, you know, during residency, a lot of our patients could not afford to see a specialist and there were there weren't necessarily easily accessible. So many of us at the community health center learned to treat happy along with hypertension, diabetes and other chronic diseases. So during that time, I really saw, you know, a lot of the difficulties that people face and getting care. And so I began really advocating and creating programs that would help people living with hepatitis B to increase screening in the communities, linkage to care, all these things that can happen in a very complex medical system. We tried to create a program to kind of streamline all of that. As I was getting more and more immersed in, you know, really providing the care that needs to happen, I really had the hat on like, you know, the physician hat like this is what needs to be done. These are the interventions. This is a science behind it. I did not wear the patient hat at all in terms of what it meant for me. And I kind of didn't feel like that. That was my role. And it wasn't until somebody did an interview. Actually, I didn't interview for CDC. And it was the first time like on camera that I had, I said, you know, I'm actually living with hepatitis B myself. And at that point, I had already occasionally mentioned it to patients. So if I was counseling a patient who had been newly diagnosed with happy and I could see they were really distraught or felt really overwhelmed. I would share with them that I also was living with happy. I was just like them. I had to go for blood tests. And I think that really helped them see that it's possible to live a happy, healthy life. And it's not a death sentence. So I was using that more often. But I never spoken about it publicly. So it took me a while. And what I've seen as a physician, which I think as physicians, we don't quite get is just how powerful that personal experience is. And I have only learned this through other people. Somebody asked me to get involved with the World Hepatitis Alliance, which is led by patients. And through that on the board, the board is all patients who represent each of the WHO regions. And I heard specifically from a good friend of mine who was now a good friend of my D Lee, who represented the Whitbro region, the Western Pacific region. He told me all these stories of people who really had had to be drastically impact their life in ways that us in medicine don't measure, right? We measure the outcomes we look at are morbidity, mortality, life expectancy, right? Sorosis, liver cancer, we don't look at outcomes in terms of somebody's quality of life. You know, when I hear these stories of how people have suffered with the burden of the disease, even if they are, I mean, as a doctor, if you were to look at them, they would look healthy. You would tell them they're perfectly healthy, their liver enzymes are normal, their viral load is low, like, you know, I only need to see you once a year, you're fine. You know, in our mind, we think it's, we think it's nothing like if you were to then delve into how they feel about themselves. And most patients won't even tell me that. So I know that what I see, what I glimpse in my exam room is just such a small part of what it means for them to live with a disease. And so, you know, it's beyond just like keeping them from getting soroses and liver cancer. You know, us in medicine, if we're, if our mission is to improve quality of life and decrease the burden of disease on people's lives, we have to think outside just, you know, our biochemical tests. I think I, you know, I've just learned that we can't afford to operate in our silos, right? The scientists cannot afford to operate in, you know, their silos, only like publishing to the scientific community and having meetings that are only for scientists and medical researchers. But we have to get out of the box. We have to combine, you know, the people living with the disease have to work in concert with the medical community for really going to make progress for elimination and for, you know, really alleviating the suffering of hep B on people's lives. Thank you so much, Dr. Wong, for sharing your story. Thank you. Hi, I'm Erin Welsh. And I'm Erin Almond Updike. And this is this podcast will kill you. Welcome to another episode. Yes, welcome. Yes, welcome. Welcome. As you have probably gathered, we are going to be talking about another hepatitis virus. Our second in the podcast history. Yes. This one hepatitis B. Yeah, we started with C. Now we're going to B. What's next? Well, I am going to mention D. I figured. I think next will be A. Yeah, next will definitely be A. And then we'll have to do E. And then maybe by the time that comes out, there'll be a few more. We can cover all in one. It's quite possible. Well, Aaron, what time is it? It's quarantine time, Aaron. It is. And what are we drinking this week? We're drinking the bee sting. We are. Hepatitis B. Hepatitis B. And what is in the bee sting? Well, it's a lovely little bev. A ginger mint syrup, some lemon juice, club soda. If you're drinking alcohol, you could certainly put some gin in it. That will be the little sting. But otherwise on its own, it is delicious. Very refreshing. I just, I love it. And we will post the full recipe for this quarantine, as well as our non-alcoholic placebo Rita on our website. This podcast will kill you.com as well as on all of our social media channels. On our website, this podcast will kill you.com. You will find any and every of the things that you ever wanted to know about the podcast. You can find bloodmobile, who does all of our music and the link to their Spotify. You can find merch, all of our merch. You can find transcripts for all of our episodes. You can find bookshop.orgifiliate.com and a good read list. You can find all of the services for all of our episodes. Thanks. I need the encouragement. And you can find our Patreon. Wow. That was impressive. Thank you. Thanks. I'm always relieved when I don't have to do it. I always get really nervous and then I just power through. I like it. It's like you get in the zone and then you're there. Well, before we get into the episode, I wanted to mention one thing because endometriosis, which is the last episode we released, is still on my mind. Even though I've been reading a lot about hepatitis B, I still have these little thoughts of endo that pop in. And I realized that there was one more thing that I wanted to say. Also endometriosis, we've recorded it. It's not yet released. And so maybe people will have already said this by the time this comes out. It's sort of a weird time travel thing we're doing here. Yeah. But in the endometriosis episode, we talked about how often complete or partial hysterectomy is recommended as like a cure for endometriosis, which it isn't. And which that can also add another dimension of pain and anguish to an already difficult disease. But I also think that another aspect to that that we didn't really touch on and I think is important to mention is that there can also be a reluctance on the part of physicians to perform hysterectomies or even just tubal ligations like getting your tubes tied for whatever reason. Even if that reason is I don't want to have any children or any more children. A lot of people are just told, oh, you're just too young, you might change your mind and want to have kids in the future. And so really that sort of another way in which many times physicians don't fulfill the very basic requirement of listening to their patient and how the social and gender role of someone can be held is like more important than what they want than their wishes. Yeah. Anyway, that just kept like circulating in my head and I was like, oh gosh, I need to say it. So yeah, okay, got it out. Yeah, that's an incredibly important point. Okay, should we should we move on to the actual topic of today's episode? Today's topic, hepatitis B, let's take a quick break and then get into the biology. People who didn't do what John of God wanted them to do, they usually disappeared. John of God was once Brazil's most famous spiritual healer, but in this limited series podcast, we uncover the darker truth behind his global empire of faith and fear. From exactly right and a Thundermedia, this is Too Faced, John of God. Listen on the iHeart Radio app, Apple podcasts or wherever you get your podcasts. So like you mentioned, Aaron, this is our second hepatitis virus. And I know for sure that during our hepatitis C episode, we talked at least a little bit about how all the hepatitis C episode we talked about. All the hepatitis viruses are named not for anything that links the particular viruses together aside from the fact that they all predominantly affect the liver. Right. So there are five predominant viruses, which we kind of already named at the beginning, ABCD and E. And today we're focusing on hepatitis B. And I will mention hepatitis D. And you'll understand why in a minute, if you don't already know the little interplay between hepatitis D and B. All right. Hepatitis B. It's in the family hepatinavira day, which essentially just means viruses that affect the liver. Like no surprise. Straight forward. One thing that's, there's a lot of interesting things about the verology of hepatitis B. And I'm probably not even going to do them justice. But here we try. Hepatitis B virus is a partially double stranded DNA virus, which is weird. So it has a genome that it's like in a little circle. And part of it is double stranded and part of it is single stranded, which is very bizarre. Do you have a question already here? And I can see it now. I mean, yes, but I'm waiting. Okay. Being patient. Okay. See if I have any answers. Hepatitis B virus has a lot of different genotypes that vary very widely in their overall geographic distribution. However, as we mentioned up top and as we'll talk a lot about towards the end of this episode, this is a globally distributed incredibly prevalent virus. Like incredibly prevalent incredibly prevalent. And it's still as far as I can tell a little bit up for debate whether these different genotypes really vary in their tendency to cause chronic infection or in their overall disease course. A lot of sources I read said that yes, different genotypes kind of have different tendencies or characteristics. And some said it's up for debate. So. Okay. But being a virus, this is of course a pathogen that has to find its way into our cells. And being a virus that infects the liver, it's unsurprising that the primary cell type that it infects is our hepatocytes, our actual liver cells. Not the blood vessels in our liver, not any of the other things around there, but generally our liver cells, the things that make up the meat of the liver. Exactly. Also called the perincoma of the liver. So fancy word for the meat. So hepatitis B is transmitted in very similar ways to hepatitis C, as you may remember from several seasons ago now, but with a few important caveats. So hepatitis B can be a bloodborne virus. So anything that involves the sharing of blood, whether that's contaminated needles in the healthcare setting or in intravenous drug use settings. It can be transmitted via blood transfusions and of course is something that we screen for to try and reduce the risk of that. But hepatitis B is also much more easily transmitted sexually compared to hepatitis C. It's present in so many bodily fluids. Why is that? It's a really good question. I imagine it is largely because hepatitis B is very, very infectious. As an example, according to WHO, it's 50 to 100 times more infectious than HIV. So I know. Do we know the reasons for that increased infectivity? That's a very good question. I do not. Okay. Yeah. And I don't also have numbers on the actual infectious dose. I couldn't find a solid answer on that either. I do know that it can persist in the environment for at least several days. So I think it's a pretty hearty virus. So that might be part of it. Interesting. Okay. So going back real quick to partially double stranded. What's what's the implication of that in like a verology sense? So it's really interesting. Hepatitis B is one of the few viruses that's not an RNA virus but uses a reverse transcriptase in order to replicate its genome. So HIV is an RNA virus that relies on an enzyme reverse transcriptase to make a form of DNA in order to then replicate. And that B also does, even though it's a DNA virus. That is so bizarre. And so I definitely came across some of that in the evolution. It's because it kind of throws a wrench in things as to like the mutation rates, the scale of the molecular clock, blah, blah, blah. Yeah. And it also, as I'll kind of talk a little bit more about later, it allows it to integrate into our genome in a way that then sets us up for both chronic infection and also potentially cancer. Right. And cancer causing mutations. Uh-huh. Spoilers. Do other viruses have this partially double stranded DNA thing as well? I don't know of any other human viruses, but I know that there are other animal hepagnoviruses that do. Right. Okay. So that's like the unifying feature of hepagnoviruses. Okay. Yeah. Yeah. Wow. Cool. Okay. So hepatitis B is also transmitted back to that part of it, vertically at much higher rates. This, let me tell you some numbers, the estimates that I read ranged from 40 to 90% of babies born to people living with hepatitis B with chronic hepatitis B will become infected with hepatitis if they are not treated. Wow. And this is in comparison to only 6% of people with hepatitis C will then transmit hepatitis C to their offspring. What is the reason for that difference? Again, I think it's largely just how infectious hepatitis B is. Okay. But here's something that I think is very interesting and important about this vertical transmission of hepatitis B. First of all, a lot of times when we talk about vertical transmission, so from parent to offspring, its wind viruses or bacteria can cross the placenta and infect a fetus during pregnancy. That is not what happens in hepatitis B. The transmission is not trans placental. In the vast, vast majority of cases, it's happening during the process of childbirth. And it's not happening during breastfeeding. It's not happening during pregnancy crossing the placenta. It's happening specifically during the period of childbirth, whether that birth happens vaginally or via C-section. What? There is some papers that suggest that C-section delivery is a slightly lower risk, but it's not conclusive. And if you've ever seen a delivery of either kind, it kind of makes sense because neither one is really less bloody than the other. And so many bodily fluids are being exchanged no matter what exit route a baby takes. It's just like the blood and bodily fluids. Blood, bodily fluids. It's thought that cervical secretions, so if a baby comes out vaginally, then that's why maybe there's some thought that it's a slightly higher risk, but the data hasn't really borne that out necessarily. What? That's very interesting. I know, because I didn't really realize that. I kind of thought that it was something that could be transmitted transpolicentally. But it's not. And that is really important when we talk about how to treat and prevent hepatitis B infection. So let me keep going, shall I? You shall. So the incubation period of infection, the time from when someone gets infected to when they show symptoms can really range anywhere from 30 days to up to six months. And I think that this incubation period, even noting an incubation period is interesting because hepatitis B is a virus that can be entirely asymptomatic. And chronic infection is generally defined as the persistence of a specific antigen being able to detect hepatitis B surface antigen for a period of at least six months. So it's interesting that you can also say the incubation period itself might be six months before you show symptoms, but you also might never show symptoms. Yeah. Yeah. That makes it really difficult to calculate an incubation. Exactly. It sure does. So let's talk briefly about what the symptoms can be if people do have kind of an acute infection or symptoms with an initial infection. Most of the time, of course, it's completely asymptomatic or very minimally symptomatic. And it's important to note that some people can clear the virus entirely from their system after an acute infection, whether they show symptoms or not. But we'll talk about how that doesn't happen for a lot of people and who those people are and why. Okay. But when symptoms do occur in the case of an acute infection, they really don't look any different from a lot of the other viruses and pathogens that affect our liver, including hepatitis C. So hepatitis B is less likely to cause acute liver failure completely. But it can cause things like jaundice where your skin can become yellow or the whites of your eyes and your gums, things like that become yellowish. And this occurs because our liver is what conjugates and helps eliminate billarubin from our bodies. And so without that process, billarubin, which is a breakdown product of our red blood cells, builds up in our skin and our eyes. And that's what turns us yellow. It then also causes a lot of nausea and vomiting from this build up of not just billarubin, but a lot of stuff in our system that our liver is supposed to filter out. It causes abdominal pain because your liver is inflamed. And even though your liver itself doesn't have sensory innervation, this inflammation can reach the lining of the liver, the lining of the abdominal cavity and cause pretty severe abdominal pain. And then all of these toxins that can accumulate in your bloodstream can cause severe fatigue. It can cause a darkening of your urine as the billarubin tries to be excreted through your urine instead of your poop. And in very rare cases, it can cause actual acute onset liver failure, which can be fatal. But much more commonly, liver failure happens as a progressive process of long-term inflammation leading to cirrhosis and fibrosis. And potentially, hepatocelular carcinoma or cancer. So I want to focus on this, this chronic infection of hepatitis B because it's not only very interesting, but it's also the most important part of this virus. So first of all, the likelihood of a chronic infection becoming established varies person to person. And it's inversely related to the age at which you become exposed and infected. So for infants, for neonates who get infected vertically during birth, the likelihood of a chronic infection is over 90%. So that means that almost all babies that become infected at birth or shortly thereafter go on to have a chronic life-long infection with a very significant risk of progression to fibrosis and or liver cancer. So this inverse relationship, is it like a straight line or does it kind of have any sort of peaks and valleys? It's not a straight line. It's a... It's a... What do you call it? No, it's a... What a... A jup, maybe? What do you say? A sigmo, yeah? So let me just tell you numbers because I'm clearly not doing a good job. Swooping. So infant neonate, 90% chance. A child, if they get infected when they're young like between ages 1 to 5, the risk of chronic infection is like 30%. So it's a pretty big drop. And then it's a little lower for older children and for adults. If you don't get infected until you're an adult, the risk of chronic infection is only about 2 to 5%. So substantially lower. Hmm. I mean, okay, I have to ask why. Glad you asked, Aaron. Let's talk about it. But first, let me also say that even though the risk of chronic infection, if you get infected as an adult, is low, the chronic infection itself and the like prognosis of a chronic infection with hepatitis B, in general, is worse than for example, the chronic infection of hepatitis C. And if you listened to our hepatitis C episode, then you remember, hepatitis C is not a good virus. Right. But in hepatitis C, the likelihood of a chronic infection is much higher for adults across the board. But the rate of, for example, liver cancer is very low, like 2.5% for people who have chronic hepatitis C. Right. For people who get infected as adults with hepatitis C, go on to get chronic hepatitis C. That makes sense. Yeah. Like, okay, in the numbers perspective. Right. But for hepatitis B, 15 to 40% of people who have chronic infection go on to have liver cancer, hepatocelular carcinoma. That's a huge percentage. Yeah. And again, 90% of infants who become infected go on to have chronic infection. So that's major. That's a really disturbingly large number. Right. Okay. So you asked why. Yeah, I did. In short, we don't fully know. That's always my answer. I'm going to cross stitch that onto a pillow for you. I would love that pillow. Oh my gosh. Okay. But so the question of why are infants who get infected more likely than adults who get infected to go on to have a chronic infection? Well, we don't fully know the answer. It likely has to do with a few different factors that relate to the various phases of this chronic infection. So a chronic hepatitis B infection, which is defined just as the persistence of the virus and like detection of these viral antigens for at least six months in the bloodstream. After that point, like after that six months point, this isn't a static infection. It's a very dynamic and it progresses through several different phases that can vary in their length and their severity. So the first phase is often known as immune tolerance. And that's essentially when our body doesn't really do much about this infection. The virus is there and one thing that it tends to do is integrate into our genome, the way that do you remember the other virus that does that in HPV? HPV, that's right. And as our cells replicate, so does this virus. But in the immune tolerance phase, it doesn't cause much in the way of damage. Then there is the immune active phase. And in some papers they call this the immune clearance phase. And this is really the meat of chronic hepatitis B infection. This is when our bodies are recognizing this virus. We are mounting an immune response to it. And therefore, we ourselves are causing a lot of inflammation and damage to our own liver cells. It's not the virus itself. And this is the phase where people are more likely to be symptomatic, like maybe have jaundice. But this is the phase where that inflammation is causing fibrosis, which is damage to the liver due to that inflammation. That fibrosis can eventually lead to scarring or permanent damage, cirrhosis. And that can ultimately lead to liver cancer. And so this is the phase, the immune active phase, that the longer that somebody is in this phase, their immune system fighting the infection, the greater their risk of cancer. But there is another phase. And that's a so-called inactive phase. We're in the virus is still there, and we've maybe made some antibodies against that virus. So we're kind of at a standstill. But at any point, people could still revert back to a more immune active infection, like say if they became immunocompromised for some reason. And therefore the virus is still there and still posing a risk of cancer development. Gotcha. That makes sense. Yeah, so I know that that was a lot. And it was really just a drive by the like immunology of hetby infection is a lot more complicated. There's a lot more detail. But one of the things that's different among adults who get infected versus infants is that infants tend to have a very long immune tolerant phase. Whereas adults who have chronic hepatitis B, that is they get infected and aren't able to clear that infection right away, they tend to not really have an immune tolerant phase, but rather progress directly to that active inflammatory chronic hepatitis infection. Right. Okay. So that's a really big difference. And it's thought that during pregnancy, viral particles or maternal antibodies or both are passing through to the fetus, and then when that infant is born and exposed to hepatitis B, while they're not able to fight off that virus entirely the way most adults who are exposed can, they instead established this relationship of tolerance that lends itself more easily to a chronic infection. Oh, right. Okay. So it's kind of like getting to know you and like, all right, I guess we'll just tolerate, you know, each other for a while. Right. But then eventually progress to the other faces of disease. Right. Okay. Interesting. But that is generally hepatitis B virus. So I have a question. You mentioned that, okay, there are people who become infected and they cleared the virus, they develop antibodies, boom, they're in the category that you didn't discuss the later stages on for obvious reasons. And so these people are now have a lifetime immunity to hepatitis B virus. What about different genotypes? Are there any sort of like genotype dependent immunity where you can be infected with one genotype and then clear that and be exposed to another one and not clear that? Great question, Aaron. As far as everything that I have read, immunity to hepatitis B is immunity to hepatitis B across genotypes. That's great news. Exactly. It's really great news, Aaron, because we in fact have a vaccine for hepatitis B. It is a recombinant vaccine that contains only the surface antigen of hepatitis B. And that is what we make antibodies to. I have a follow up question. Okay. If someone is chronically infected with one genotype of hepatitis B, can they become infected with another genotype of hepatitis B? Not as far as I know, but do you know what they can become infected with? Hepatitis D. Hepatitis D. Thanks for the little intro there. You're welcome, you're welcome. I want to just very briefly mention hepatitis D because I don't think that we would ever do a full episode on it. I don't know, maybe I'm wrong. But delta hepatitis virus or hepatitis delta, hepat D. It's a fascinating virus. This virus belongs to its entire own viral genus that doesn't have an actual family that it falls within. And some people say it's not even really a virus. It's like something else entirely. It's a sub-viral agent. Whoa. What? It's like a virus of a virus. It's kind of. So hepatitis D has an RNA genome. And it can replicate on its own inside of our cells. And when it infects us, and it does infect our liver cells. But it can't actually infect our cells by itself. It relies on the surface proteins of hepatitis B virus in order to get into our cells. And in order to be released from our cells. So hepatitis D is a virus that can only infect someone who has a chronic or acute hepatitis B infection. I'm really regretting right now not reading more about the evolutionary origins of hepatitis D. Because what on earth? Maybe it does deserve its whole own episode. Yeah. That's literally all I have to say about it. But it is very, very interesting. Okay. So what about besides the vaccine, what about treatments? Are there antiviral treatments for hepatitis B virus or maybe hep B and hep D combined? Yes. For hepatitis B, there are. So there's a number of different treatments that we have actually. None of them can cure hepatitis B. They're all used to sort of manage it and to try and reduce the rate of inflammation and complications. But pigillated interferon, which I think we talked about in our hep C episode, possibly. But that's basically like an immune modulator. You can think of it as that can be used and has been used to treat hepatitis B. But there are also a number of antivirals that in many cases are used to treat HIV or work used to treat HIV. And are now used to treat hep B. So yes, there are. Again, none of them actually clear the infection, but they all just sort of helped him manage it. Okay. And what's really important about all of these is that because all of those different states, immune tolerance, immune active, inactive, these different phases of infection, really very person to person and how severe someone's symptoms might be. Like it really varies. So just because someone has an infection with chronic hepatitis B, doesn't necessarily mean that they have to be on treatment. If they're in a phase that isn't directly causing damage. Does that mean that? Yeah, that's interesting. At least as of now, because the treatments that we do have are not with outside effects and in a lot of cases, they have quite a lot of side effects. So it requires a lot of careful monitoring and everything which makes it a lot harder to do quite honestly. There's so much here about this virus. I know. So speaking of so much about this virus, Aaron. Like, where did it come from? What the heck? I will do my best to answer those questions, but let's take a quick break first. All right. The story of hepatitis B. I feel like in the last couple of episodes, I've maybe deviated a bit from the normal history overview that I usually give. But don't worry, I'm going back to my roots for this one. I'm going to start with a bit of evolutionary history, mix in some early accounts of infectious hepatitis, then the fascinating story of its identification, and then finally getting us to where we are today. The usual. The usual. I love it. But usual doesn't mean boring or straightforward, especially in the case of hepatitis B. So beginning at the beginning, where does the hepatitis B virus come from? It turns out that the answer to that question has been a moving target for a number of years, with new hypotheses introduced or old hypotheses overturned or tweaked to fit new findings. As more about the evolutionary history of this virus has come to light. And this should come as no surprise really considering how widespread this virus is, how many genotypes there seem to be, how the virus can undergo recombination, the confusion about its partially double stranded DNA, and how we don't really know exactly maybe the rate of evolution or mutation. There's been a lot of work on this. I was happily surprised to find, especially recently. And so I'm going to try to bring us up to speed on what the current consensus is, relying mostly on two papers that came out in 2021 about the origins and evolution of the hepatitis B virus, one by Lokrnini et al and the other by a coach or et al. Like you said, Aaron, the hepatitis B virus belongs to the hepatinavirida family. And in the years after the hepatitis B virus was first identified, researchers found viruses belonging to that family that infected birds, fish, reptiles, amphibians, other mammals, non-human primates, etc. Basically, this is a lot bigger and a lot older of a virus family than we thought with there and there are some estimates that it originated around 82 million years ago. Whoa. So like this thing was infecting birds. Essentially. Yeah. Back when birds and dinosaurs were the same thing. Yeah. I hope that that's probably not accurate, but you know what I mean 82 million years. Let's stick with that. Yeah. So from 82 million years ago, how did it get into modern humans? And on that, there seems to be some debate. Surprise, surprise. For a long time, it was thought that hepatitis B virus originated in Africa or for a while it was thought maybe the Americas. And then it spilled over into humans, possibly from like a non-human primate and then dispersed. Maybe it was dispersing out of Africa following prehistoric patterns of human migrations. But more recently, that assumption has been questioned. So one of the studies published in 2021 used hepatitis B virus detected in skeletal remains of 137 individuals found in Eurasia and the Americas, and dating between 10,500 years ago and 400 years ago. What? That's some old viral DNA. I just love it when you find things like this, Aaron. I know. It's this paper was really interesting. It also had the most authors of any paper I've ever seen. I think it was 170 something. Oh my goodness. Uh-huh. That's more than like the whole human genome paper. But I mean it makes sense because I'm assuming that there was a lot of collaboration across many different universities with all of these remains. Yeah, skeletal remains. So, okay. Anyway, so what this paper using all of these old skill to remains with hepatitis B virus did is that they wanted to reconstruct the evolutionary history and dispersion of the virus. And what they propose is that the most recent common ancestor of the hepatitis B virus dates back to around 12,000 to 16,000 years ago, which is more recent, actually, than was previously thought. And it places that most recent common ancestor in Eurasia, where over the next hundreds and thousands of years, it spread across Eurasia into Africa through Europe and to the Americas. It seems like the emergence of the hepatitis B virus and some of it spread happened before the Neolithic Revolution, which is when people began settling in larger groups and farming and so on. And if you think about it, this completely makes sense. Because what are some of the transmission characteristics that hepatitis B has? People can be carriers, it can be transmitted to a baby at birth, it can be spread during sexual contact or through blood, so like violent interactions or tattooing even. There are many different ways that this virus can be transmitted. And the fact that there are people who can carry it for long periods of time means that it doesn't need this critical population size in order to spread or persist in a population. So in that way, it's a lot like a couple of the other viruses that we've talked about before, like the Herpes Simplex virus or Chickenpox virus. But once people began settling in larger groups around 7000 to 8000 years ago, that meant of course more opportunities for transmission, which led to an increase in the diversity of hepatitis B virus strains and the emergence of multiple genotypes or lineages. I'm not going to go into a ton of detail about this, but the paper that I keep mentioning by kosher at all actually trace the kind of like rise and fall of different hepatitis B virus lineages. So one for instance, seemed to be the prevailing lineage in Western Eurasia for like 4,000 years, but then it disappeared around 3,300 years ago. It just went almost extinct. No idea why, maybe sampling bias, maybe a reduction in human population that kind of like bottlenecked it or eliminated it, or maybe it was like intergenotype dynamics, who knows. So interesting. I find this so fascinating. And this pattern of genotypes going extinct and shifts in the predominant genotype, it still happens today. And we don't know for sure, but maybe it's partially due to the fact that some genotypes may be associated with certain transmission roots I've seen. And maybe some of the genotypes vary in their ability to cause severe disease or in their ability to cause this persistent carrier state. And so that's I think why it's really important to understand the origins and the evolutionary history of a virus like the hepatitis B virus. It can tell us in part why we see some of the epidemiological patterns that we see today. And it might be helpful for predicting what we could expect to see in the future. Okay, so we have this virus that has ancient roots and that had reached a global distribution a long time before the present day. And I already mentioned that evidence of hepatitis B infection has been found in ancient human remains dating back thousands of thousands of years, as well as just a couple thousand years, as well as more recent. So basically it's kind of like persisted in human populations for all of that time. But were the people who were around back then aware of this? Like did they have any idea? Were they? Did they? Well, probably, in a sense. So jaundice, which can be caused by many different things, including the hepatitis B virus, has long been recognized and described in ancient medical text. Well, I'll toss in the Hippocratic texts from around 400 BCE because it's an episode of this podcast. What kill you? And outbreaks of jaundice were also written about. So one paper I read suggested that there was a description of what was likely infectious hepatitis dating back to the 8th century CE. And it was sometimes called campaign jaundice because it seemed prevalent during times of war. Surprise, surprise. But switching from talking about the evolutionary history of the hepatitis B virus to the written human history part, it's tricky because of the existence of other hepatitis viruses. Hepatitis B. We can test human remains for hepatitis B virus specifically, but we can't always know which hepatitis virus was causing whatever outbreak that was being described. How likely was it that it was hepatitis B? In terms of outbreaks, I would guess actually that the hepatitis A virus, which is transmitted fecal orally, may have been the culprit more often than not, especially in crowded or unsanitary conditions like war. Yeah. And especially in any that were like acute infections. Yes, like, mm-hmm exactly. But it's certainly possible that hepatitis B and other hepatitis viruses transmitted through blood or bodily fluids caused outbreaks, especially as the use and reuse of needles became more popular around the middle of the 19th century. So let's fast forward to then the last decades of the 1800s. Let's this is like after the development of germ theory and after the introduction of some injectable vaccines. In 1885, an epidemic of jaundice followed a smallpox vaccination campaign among ship workers in Bremen, Germany, which led to what seems like an early indication that hepatitis outbreaks could be caused by the reuse of needles or because this particular vaccine used like human serum as a stabilizing agent through like blood products. But the link between the administration of this vaccine and the resulting hepatitis outbreak, it wasn't recognized for decades, possibly obscured by this longstanding recognition that epidemics of hepatitis or jaundice were also known to frequently happen in overcrowded unsanitary areas. So it was more difficult to pinpoint the vaccine itself as the cause rather than like, oh well, maybe they all went to the same watering hole to the same to the same watering hole where they all got hepatitis. Yeah. Yeah, but as blood transfusions increased and the practice of reusing needles persisted, there was this growing suspicion that an infectious hepatitis might also be carried in the blood or blood products. See our hepatitis C episode for more on the history of blood transfusions and the blood typing system and so on. Yeah. The differentiation of two different hepatitis is one called transfusion hepatitis and the other one being called infectious or food or waterborne hepatitis. This was finally made in the early 1940s during World War II hundreds of thousands of US Army personnel received the yellow fever vaccine, which like the 1885 smallpox vaccine had human serum as an ingredient. Obviously that's no longer done for safety reasons needed to maybe clarify that. But after receiving this vaccine 50,000 people came down with hepatitis, although those were just the clinically recognized cases. Right. Later estimates put the total figure of hepatitis infections resulting from this vaccination campaign at around 330,000. Oh dear. Okay. Oh gosh. Oh dear. Okay. It's a lot. It's a lot. Yeah. And there was a British doctor named FOMA Calum, who had been involved in the development and administration of this vaccine. And he hypothesized that it might have been transmitted by reusing syringes or carried in the vaccine itself. And he thought that this hepatitis represented a bloodborne infection, separate from the previously recognized food and waterborne hepatitis. He proposed that they be called hepatitis A and B, and that they may represent different viruses. So this is how it begins. This is how it begins. Because at the time it was like not known whether it was the same virus or different viruses. And so it was more in like the clinical picture of it in a way. Yeah. Because after this designation, after this recognition that like, hey, this might be transmitted through blood products and not just through like food and water or whatever. Other researchers began to describe differences in the way that these two hepatitis looked clinically. And to kind of keep an eye out more on the different roots of transmission. Right. Once you have it more like, hey, there are two different things here. Then you start to notice more of the differences. Right. Once you create those like columns, then it becomes much easier to add to the list. Eleven. Yeah. But just because people now knew that hepatitis could be transmitted by reusing needles or via blood products, that didn't mean they could stay. And so, I think they could stop it from happening. Like I talked about in our hepatitis C episode, blood transfusion or blood product technology vastly outpaced our ability to identify many bloodborne pathogens, especially viruses, which led to blood products that were unknowingly contaminated. And often it was seen as this kind of situation where, you know, it was like, well, we don't know whether or not this batch of blood has hepatitis virus in it. But you can either receive the blood and possibly get hepatitis down the line or not take the blood and die of blood loss immediately. So there was like no choice sometimes. There's no option. That's not to say that people weren't working on finding a way to test the blood supply and identify what was causing the hepatitis. If anything, it was that feeling of being powerless to protect people from this disease that created a sense of urgency in finding out what the hepatitis B agent was so that they could detect it in blood products. But despite a ton of people working on this, progress kind of stalled in the 1950s and early 1960s. And I think it stalled partially because this was a time when verology was kind of in its infancy as a field. And the technology that would allow for genetic testing or sequencing was still decades away. I'm sorry. I just... I had... I don't know how I didn't know that it was so recent. I know. Like 1950s, 1960s, that's not a long time ago. It is all of the hepatitis viruses are like have very recent identification dates but have been recognized for decades before that. And it's just sort of this like constantly unfolding tragedy where you're just like you see it and you're like and they know like the people who were there at the time are like I can't... Like this might have hepatitis virus in it but I can't do anything about it. But I don't know it. I know it but I can't know it. And we can also blame the virus itself because this isn't to say that verology research on all fields, on all viruses, had stopped or stalled by the early 1950s or 60s. Because some were easier to work with in a lab setting than others. And hepatitis B virus doesn't really lend itself very well to culturing in a lab setting. And so it was just more difficult. Especially if you don't know even what you're looking for. How do you know that you're on the right track at all? Yeah. And it's a weird virus. Where did he set that? Yeah. It's a weird one. It's very weird. And at the time it wasn't... people were using the term virus but it wasn't known for sure whether it was a virus or something else. It was like known to be a virus in concept but without physical proof. But by the end of the 1960s that would change. And the team that led to the breakthrough identification of the hepatitis B virus would not have been on anyone's short or even long list of people that were likely to have done the job. Why? Who with it? Okay. I'll get there. But before we get into the unlikely story of the discovery of the hep B virus, I want to quickly mention the Willowbrook State School hepatitis studies. Which were these unethical experiments that are sometimes referred to as the pediatric Tuskegee. Oh dear. Yeah. I'm going to be brief because these studies are mostly about hepatitis A. And so when we do a hep A episode, I'll go into more depth on them. But I wanted to bring them up here because these studies mark one of the major points in the history of medical ethics. And also hepatitis B was a part of these studies. So Willowbrook State School was a state-funded institution established in 1947 on Staten Island, New York for children who were intellectually or developmentally disabled. I hate this already, Aaron. I know. I know. In 1958, Infectious Disease Physician Dr. Saul Krugman from New York University and Bellevue Hospital, he was asked to join Willowbrook to help figure out why there were such high rates of hepatitis among the children there. With something like 30 to 50 percent admitted there would end up getting hepatitis. And they also asked him to help bring those rates down. And so he agreed and set out to not only bring down the rates of hepatitis, but also to, quote, describe the circumstances under which the disease occurred. And the effect of gamma globulin and reducing its occurrence and an attempt to induce passive active immunity by feeding virus to persons protected by gamma globulin. And to describe the excretion of virus during the incubation period of the disease. Oh dear. Your face tells me you've picked up on some of the, yeah, yeah, problems with these studies, intentionally infecting children. Yeah. So Krugman justified the research by saying that the children would inevitably get hepatitis anyway because it was so prevalent in the school and that this way with his experiments of vaccine could be developed and tested. Parental consent was obtained, but it's not clear the extent to which parents were told of the risks to their children and what exactly was involved. By his own estimation, Krugman studies reduce the incidence of hepatitis by 85%. Again, it's not entirely clear which hepatitis. But his study did demonstrate that there were two different types of hepatitis transmitted in different ways, which like I said was already kind of known, and also tested a prototype of a hep B vaccine, which did seem to be somewhat effective. The legacy of the Willabra hepatitis studies is that the resulting outrage led to very strict regulations placed on including children in clinical trials and medical studies and more revamping of what could be considered medical consent. There's a lot more of course, like I said to these studies and their place in the history of medical ethics. And so if you're interested in learning more and don't want to wait for our hepatitis A episode, I will list some sources for this on our website. And there's also a paper that Krugman wrote and published in 1986 in which he defends himself and the research. So that's kind of an interesting read. There's like a lot of discussion about this and I didn't do it justice. So let me just say that. Wow. Yeah. Okay. Okay. Back to strictly hepatitis B. So by the 1960s, the hepatitis B virus had still not been identified despite the fact that tons of people were working on this problem. And when it was finally discovered, it wasn't by one of those researchers who had dedicated their lives to hepatitis. Oh no. But by a team who had not even been looking for hepatitis B or any other virus. What were they looking for it? I feel like this story is such a good example of how science like rarely proceeds in an orderly fashion. It's not A to B to C. It's especially because B happens to be the first hepatitis virus to skewer. Yeah. Okay. I saw that on a timeline and I was like, whoa, whoa, whoa, hold on, hold on. I was like, why is that called B then? Yeah. It doesn't make any sense. Uh, yep. Everything's just arbitrary. Okay. Cool. Cool, cool, cool. Yep. But yeah, it's like we often tell like I'm including myself in that. These stories of scientific discovery in a very linear way and a very like here's this nice little pretty narrative packaged. And that neat narrative does serve a purpose because it kind of is like, well, let's find the important things. Let's find the compelling things. Yeah. But that's not the way things happen. It's just simply not. And so this I think really illustrates that. Sometimes you're looking for one thing and you end up stumbling upon something that never even crossed your mind. So let's meet Dr. Baruch Bloomberg. Okay. Hi. Since early in his career, Bloomberg became interested in why some people get sick and others don't. How genetics interacts with human behavior and the environment to lead to disease, basically. And he became interested specifically in polymorphisms. So these are genetic traits for which there are multiple forms. So things like tongue twisting. Can you twist your tongue? Yes. Can you? You too. Cool. Blood types. What blood type are you? I'm opositive. I'm AB positive. I knew that about you. I knew that about you. So these are examples of polymorphisms, right? Like there are different forms of these and there are different distributions in human populations. And so he wanted to see whether there were any of these polymorphisms that were associated with susceptibility to certain diseases. So kind of like asking the question, do people with type A blood have a greater chance of developing heart disease? And if they do, why? But instead of blood types, which at this point had already been pretty well established, Bloomberg was interested in finding new blood plasma protein polymorphisms. That could be associated with variation in disease susceptibility. So that's what he was looking for. He wasn't even looking for virus. No, he was looking for blood plasma protein polymorphisms. Wow. I've already found some proteins, all right? He certainly did. But how did he find these proteins? Yeah. Well, he began his search by collecting blood samples from people all over the world and then testing them to see whether certain antigens appeared and in what frequency. Basically, you used the blood of someone who had received multiple transfusions to find antibodies against a protein antigen that was new to them. And then you tested those antibodies against other blood samples to see how frequently it reacts, meaning how often that protein antigen is present. Yeah. And this might seem like a very crude approach today in the days of super inexpensive genomic sequencing. But back then, these were the early, early years of genetics. I mean, we still do that to do regular blood typing. Yeah. So it's still very useful. So it is super useful, but the approach like the technology that he used, which was Agargel diffusion, it was basically like one of the only ones available at the time. Immunology was in its infancy. Uh-huh. And so with this approach, Bloomberg and his team identified a new protein that they called the Ag protein, AG for antigen. This protein, which they found to have an uneven global distribution, turned out to be a serum lipoprotein. So serum protein combined with fats that may play a role in serum cholesterol and triglyceride levels. Maybe not a strong marker for disease susceptibility, but it was an encouraging finding. It showed that their technique, even though it was, you know, maybe a little bit kind of rough-handed, could be used to find new serum proteins. So they kept looking. For the next hunt, Bloomberg teamed up with a blood researcher named Harvey Alter, whose name you should recognize, farmer hepatitis C episode, except when I looked through my notes for his name, I didn't mention that he was the person who identified the hepatitis C virus, and I am so embarrassed. Like, that's kind of a fundamental important person for the history of hepatitis C. I bet you talked about a lot of important things, Aaron. I'm just, I'm ashamed. You know. But I am, I'm mentioning him here, and I also want to shout out that in 2020, he was awarded the Nobel Prize for his role in hepatitis C research. Oh, cool. Wow. Yeah. So anyway, Alter, who was in the beginning of his career in the early 1960s, he was interested in why some people developed an immune response, like a fever, chills, a rash, etc. After receiving a transfusion. Ooh. Yeah, interesting stuff. And it took a little bit of time, a little trial and error, but Alter and Bloomberg found another polymorphism. And this they named Australia Antigen, because it was first found in the blood serum of a First Nations person from Australia. And we've talked about the problem with place names to describe a disease loads of times before. However, I want to point out that at the time this Australia antigen was just thought to be a human protein, not necessarily an actual pathogen, which surprised him spoilers. It turned out to be. But in any case, the name Australia Antigen didn't stick around for very long, because it was soon shown that the Australia Antigen was actually the hepatitis B virus. I love this story. I know. I know. I just think it's so amazing. It's like, I don't know. It's just such a fun story. So how did they make this connection? Well, first, after finding this new protein, they decided to look at its geographic patterns of prevalence, just like they had for their earlier ag protein, which, you know, was it more common in some areas or in some populations than others. And they did find variation in the global distribution. They found that the Australia antigen seemed to be somewhat rare in the US blood samples that they had, but it was a little bit more common in parts of Asia, in the Pacific, Africa, and Eastern and Southern Europe. They also showed that the antigen seemed to cluster in families, which at first glance suggested that it was an inherited tree. But as more data came in, that assumption kind of broke down. Yeah. Uh-huh. Bloomberg and his team began getting suspicious that it might not be a human protein, after all, but rather an infectious agent, one that was possibly bloodborne, as they had found it in several people who had, at first, tested negative for the antigen, but later tested positive shortly after receiving a blood transfusion. Oh, no. And then the connection to hepatitis B fell into place when they began to find the antigen at high rates in people who had hepatitis. Okay. Especially those with the history of transfusion. Mm-hmm. By 1965 or so, they had become convinced that they had finally found the long sought after hepatitis B virus, almost by accident. Wow. Truly by accident, really. Yeah. And they sent off a couple of papers to be published. One was outright rejected, with a reviewer commenting that there simply wasn't enough evidence in support of their hypothesis. And now we look back on this and go, that's absurd. How could this monumental finding be rejected? But if you consider this in the larger context of the time, it does seem like it was kind of like a boy who cried wolf scenario. People were always submitting articles saying, I found the hepatitis B virus. I found it. It's this. It's this. Kind of like how I feel like every few months nowadays, there's an article saying the zodiac killer has finally been identified. It's like, okay, let's, if we dig a little deeper, like, is it true or is it not so close? Not so close to the truth. But another reason for the rejection. And this one is much more unfair is that Bloomberg and his group were in no way part of the hepatitis B scene. They had no background in studying hepatitis. None of them had been trained as epidemiologists, let alone virologists. So what did they know about hepatitis? Yeah. But despite this initial rejection and the resentment from some prominent hepatitis researchers, they managed to get the paper published in 1967 that awakened the world to the possibility that the virus causing transfusion hepatitis, the hepatitis B virus had finally been found. 1967. Wow. Yeah. And this seems like an understatement, but this was huge news. Yeah. At the time, post transfusion hepatitis rates reached 30%. Oh my. Mm-hmm. The beginnings of the incredible prevalence of global hepatitis that we have today really does have its roots during this time, during this time when there was a lot of blood transfusion happening, a lot of blood products being used, a lot of needles being reused without knowing what the virus was, how to test for it, how to prevent it. So it's. Yeah. But there was still another step and that was confirmation from other researchers. Boom. Easily done. Check. Here's hepatitis B. The end. Almost the end, actually. The discovery of the hepatitis B virus. This, this allowed not only for the testing of hepatitis B virus and blood products, but also the identification of carriers of the virus and the eventual development of a vaccine. This isn't to say that it was all smooth sailing after the link between the Australia antigen and the hepatitis B virus was made. For instance, the virus was still not able to be maintained in conventional tissue cultures, which made fulfilling coaxed postulas difficult. And the test for determining whether or not the virus was present, you're pretty insensitive at the time. Mm-hmm. Like I've seen estimates of 15 to 20% of the time it would detect hepatitis B virus. Yeah. That's pretty bad. It's gotten a lot better. We should point out a lot. Yes. That's, like, very good. Like, excellent. Yep. And as I always talk about, there's typically this delay from when something new is discovered to when there is wide enough acceptance for that knowledge to be applied, especially in like a medical setting. So screening the blood supply for hepatitis B, even with this, you know, pretty poor test, didn't start for a few years after the virus was discovered. So in 1970, the hepatitis B virus test became official in the US, and in 1972, the American Association of Blood Banks had begun to require the testing of donors. And even though the test desperately needed to be improved, that was a good start. But being able to test for hepatitis B virus also meant that it could identify people who were carriers or infected with hepatitis B, which then led to widespread discrimination and ostracization for people who were positive for hepatitis B. People were fired from jobs. We were not allowed in classrooms. Children were taken off adoption lists. People were being denied health care from shared machines like dialysis machines. They were being denied admittance to medical school or kicked out of their jobs as doctors or dentists. I mean, the list goes on and on. It was just like, oh, great. We have this test. We can help prevent hepatitis. And also, we can put a, the scarlet letter of hepatitis on every single person that we test. I feel like that part of hepatitis B especially is so overlooked today. Mm-hmm. Like, yeah. Yeah. Yeah. And yeah, a lot of these many, or most of these restrictions or regulations have been overturned. But the stigma and isolation faced by many people with hepatitis B continues today and has a huge detrimental impact on their quality of life. Right after the hepatitis B virus was identified, many people began working on a hepatitis B vaccine, including Bloomberg and his colleague, Dr. Irving Millman, who came out with one in 1969. And over the next decade, people would work on refining the vaccine and incorporating it into routine vaccine schedules. And I think since then, it's kind of face like continuous like tweaking and we've gotten a pretty solid from my understanding hepatitis B vaccine. Yeah, since 1981 was when the hepatitis B vaccine was licensed like in the US widespread by the FDA and then 1986, it was updated to not have any like human parts in it essentially. Right. It's made in a yeast and it's a recombinant vaccine. And as far as I know, it's the same vaccine since 1986. You know, who helped work on the yeast aspect of it? Tell me who Aaron. Maurice Hilliman. Oh, it's here for Maurice. And I already mentioned one person in this story who was recipient of a Nobel Prize for their work on hepatitis viruses. And that was in 2020. But in 1976, Dr. Beruk Bloomberg was awarded the Nobel Prize in Physiology or Medicine for his work in identifying the hepatitis B virus. Love it. Also, that same year it was co-awarded to two different people just to, you know, that didn't have any work together. The other person awarded was Carlton Gaggesick. Do you remember him from Priyans, the bad guy? Yes, I do. Uh-huh. Ugh. Over the decades since the discovery of the hepatitis B virus, there's been a great deal of research on understanding transmission dynamics, genotype differences, the cancer causing potential of the hepatitis B virus, new hepatitis viruses, like hepatitis D, like hepatitis C, like hepatitis E, better blood tests, improved vaccines, harm reduction programs, and a growing recognition of the tremendous global burden that this virus has in a physical, economic, and emotional sense. And despite all of the advancements made in the field of hepatitis B research, the virus is still extraordinarily prevalent and transmission continues today. So, Aaron, that was kind of a quick wrap up to the future, but I want to hear where we stand with hepatitis B today. So, can you film me in? Oh, I can't wait to. Right after this break. I'm like our first three episodes. I have some, a lot of statistics for this section, Aaron. First three episodes of the season, I mean, but they're pretty sobering. Okay. Globally, it is estimated that close to 4% of the entire world's population is living with chronic hepatitis B infection. That is close to 300 million human beings. And believe it or not, that's an improvement because the very first paper I read was a bit older from 2004, and that started off by saying over 400 million people. So, we're down. So, those are people chronically infected. Right, living with chronic hepatitis B. And how many people are infected newly every year? Let's see, incidents. The World Health Organization estimates 1.5 million people are newly infected every year. Wow. That's... Yes. It's horrific. If we look at the entire spectrum or the whole alphabet of hepatitis B, or viral hepatitis B, viral hepatitis caused an estimated 1.34 million deaths in 2015 alone, which is more than HIV, it is substantially more than malaria, and it's nearly as much as tuberculosis. So, why does it feel like it's not talked about? Why, Erin? I don't know. Okay. And that's all of the viral hepatitis, hepatitis. Okay. Of all of those deaths, 96% are estimated to be from chronic hepatitis, and of that 96%, 66% of those are from hepatitis B. So, if we do some Erin math, just kidding. Just kidding. The World Health Organization did this. That is 820,000 humans that are dying from chronic hepatitis B infection every single year. Now, you asked why we're not talking about it. Yeah. Here's probably a large part of it. That burden is not born equally across the globe, of course not. The World Health Organization divides the globe into different regions. The Western Pacific region by far has the highest incidence and prevalence of hepatitis B followed by the World Health Organization African region. And in these areas, the prevalence can be as high as 6% or greater in some cases. Wow. Oh my gosh. Whereas in some parts of the world, like in Europe or in North America, the prevalence may be less than 1%. And so, I think that huge global discrepancy can lead for some countries to not think a lot or talk a lot about hepatitis B. Yeah. Oh well, it's not a problem here, so. Exactly, Erin. I think I wrote those exact words later on. Yeah. And it gets more sobering because it's also estimated that only 10%, 10.5% of people that are living with hepatitis B know their status. And it's also estimated that only 22% of those that are diagnosed that know their status are on treatment for chronic hepatitis B. That statistic I want you to take with a grain of salt because not everyone who is diagnosed with chronic hepatitis B necessarily needs treatment at least not right away. So that statistic at least might not be quite as bad as it sounds, but 10% of people knowing their status is pretty bad. Yeah. That's, I mean, that's, yeah. Yeah. It's also I have more numbers, this is a number heavy one. And these numbers are from a modeling study from 2016 data. But of this almost 4% of the global population that is infected with chronic hepatitis B. Between 1.6 to 2.2 million are children under the age of 5. Mm hmm. And the World Health Organization, most recent data does suggest that it's now finally just under 1% of all children worldwide under age 5 that are chronically infected. That's down from around 5% of all children in the pre-vaccine era. Oh my gosh. And still like just under 1% and essentially 1% of all kids under age 5 globally living with this chronic infection. That I can't emphasize enough is entirely preventable at this point. We have had a vaccine for hepatitis B that is 98 to 100% effective for 17 to 30 years. Like not a lot of waning immunity, incredibly effective vaccine for 40 years. So I have a question about that. Uh huh. So is it part of every single routine vaccine schedule? Over 180 countries have hepatitis B as part of their universal vaccine program. And it's estimated that 87% of infants worldwide received the three dose B vaccine series in their first year of life, which is great. But only 46% likely had a timely birth vaccination that critical 12 to 24 hour window. And even less the study estimated about 13% got both the hepatitis B vaccine. And if needed that IVIG to actually treat and provide more passive immunity. Right. But with IVIG and the vaccine within 12 to 24 hours of birth, it's still about 91% effective to prevent hepatitis B infection in those babies. But it's even more effective if you can treat the pregnant person to lower their viral load. Okay. And it's estimated that only about 1% of pregnant people are actually getting that testing and the treatment. And so that contributes a lot to the overall burden and why we still have such high infection rates. We have the tools just not the delivery. Yeah. So we have a lot of improvements to still be made. Yeah. Overall, this is a massive, massive disease. I honestly didn't even realize how massive it was before researching for this episode. And because it's such an enormous global problem, I'm glad that we were able to highlight so many different parts of this really important disease. But there are still several aspects that we didn't fully cover in this episode, especially the substantial stigma and discrimination faced by so many people living with hepatitis B around the world. Right. And because this is such an important part of the hepatitis B story, I am so excited to be able to take a deeper dive into it in a bonus episode coming out next week. Woo-woo, you heard that right bonus episode. So I enlisted the help of the amazing Dr. Sherry Cohen, who is Senior Vice President of the Hepatitis B Foundation, to discuss some of the drivers of stigma and discrimination in hepatitis B. And what's being done about it? I also got to pick Dr. Cohen's brain about what it's like to work in the public health nonprofit world, what the differences between a doctor of public health and a PhD is, and some fantastic advice for people who might be interested in pursuing a career in public health. And we know there's a lot of you out there. There's a lot of you out there. Yes. It was so much fun chatting with Dr. Cohen, and you should definitely mark your calendar so you don't miss the app. It comes out next Tuesday, February 1st. Okay. But should we maybe wrap up this episode for now? I think we should. Time for sources. It is. All right. So I have a lot of papers for this. And I'll post them all on our website, but I do want to shout out one book in particular. And that is of course hepatitis B, the hunt for a killer virus by Dr. Brueck Blumberg. I have a few papers, not as many for this as some episodes, but a few really nice review papers. Most of them are from the Lancet, and they've just been like updates on each other. The most recent one that I read was published in 2018 and called chronic hepatitis B virus infection has a lot more detail about the different phases of chronic infection. And we'll post the sources for this episode and every one of our episodes on our website, this podcast will kill you. We sure will. I big thank you again to Dr. Wong for taking the time to chat with us and being willing to share your experiences with hepatitis B. And also thanks for all the awesome work you do. Yeah, thank you so much. Thank you also to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to exactly right of whom we are a very proud member. And thank you of course to you listeners. We love making this podcast and we couldn't do it if you didn't listen to it. It's that's very true. And also an extra big thank you as always to our wonderful patrons. We love you. You're amazing. We love it. Okay, well, until next time, wash your hands. You filthy animals. You're a very good person. You're a very good person. You're a very good person. You're a very good person. You're a very good person.