This Podcast Will Kill You - From the Vault - Hepatitis B: Hepatiti, Take 2 (Ep 89)

Episode Date: December 23, 2025

This episode originally aired on January 25th, 2022. In light of the recent changes by RFK jr’s Advisory Committee on Immunization Practices (ACIP) to eliminate the universal birth dose of the hepatitis B vaccine in the US, a decision which will result in preventable infections and deaths in this country every year, it seems timely to remind everyone of the global consequences of this incredibly prevalent pathogen. This week, we’re dipping a toe back into the vast waters of hepatitis viruses, this time with a focus on hepatitis B. The hepatitis B virus, though second to be named, was first to be discovered, and effective vaccines and treatments have been available for decades. Yet the global prevalence of this virus remains staggering, with nearly 300 million people chronically infected and 1.5 million new infections annually. So what’s going on? In this episode, we weave our way through the complicated biology of this virus and its deadly potential, the strange history of its identification that shows that you don't have to be looking for something to find it, and the current status of this virus that underlines how safe, effective tools for disease prevention are only as good as our delivery infrastructure. We are also so excited to be joined by Dr. Su Wang, Medical Director for the Center for Asian Health & Viral Hepatitis Programs at the Cooperman Barnabas Medical Center and outgoing President of the World Hepatitis Alliance. Support this podcast by shopping our latest sponsor deals and promotions at this link: https://bit.ly/3WwtIAuSee omnystudio.com/listener for privacy information.

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Terms and Conditions Apply. Visit blueapron.com slash terms for more information. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies. 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious.

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Janice Torres here. And I'm Austin Hankwitz. We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio in partnership with Intuit QuickBooks. We're back for season four to talk to some incredible small business owners. The big thing about working at tech is that it's ever evolving, ever changing. everyone's a rookie. That's how fast the industry is changing. So what I'm really excited about is to be part of that change. So listen on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Virgin Voyages Presents with Love from Alaska.

The scenery out here is unreal. Mountains, glaciers, waterfalls, the ship? Designed for panoramic views, which is why I'm pretending to be a wildlife photographer. I am not. Yesterday we were hiking and kayaking. Today, I'm watching for humpback whales. Anyway, wish you were here. Award-winning Kid-Free Alaskan cruises from Virgin Voyages with immersive shore excursions and zero kid energy. Virgin Voyages.com. My name is Sue Wong. I am a physician.

I'm a MD-M-PH. I'm the Medical Director for the Center for Asian Health and Vital Hepatitis Programs at the Cooperman Barnabas Medical Center in New Jersey. and I'm also just coming off a two-year 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, right, 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-bed student, but honestly, I didn't know anything about Hep B. I called my sister confided in her about this new diagnosis. And she said, oh, didn't you know, mom also has Hep B? 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. I 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 Hep B vaccination and statuses. And I had indicated that I was a carrier and didn't hear anything about it. I didn't think anything of it. And it's not till now that I've heard numerous people who are in med school found out to have Hepby and actually they lose their acceptances to med school or they face 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 it 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 attentively. And when I got to residency 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 it. I hadn't 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, you know, 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. And 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 want 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 hepbee. 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 stay and age. And so as a physician, 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 Hep B than I ever knew that it's one of the most common infectious diseases around the world up to like one in 10 of our patients had Hep B was as common as 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 weren't necessarily easily accessible. So many of us at the Community Health Center learned to treat Hep B. 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 in 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 and 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 the science behind it. I did not wear the patient had 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, a case. I occasionally mentioned it to patients. So if I was counseling a patient who had been newly diagnosed with Hep B, and I could see they were really distraught or felt really overwhelmed, I would share with them that I also was living with Hep B. 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 mine, Dee Lee, who represented the Whippro region,

the Western Pacific region. He told me all these stories of people who really had had be drastically impacted 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? Cerosis, 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, 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 cirrhosis and liver cancer, you know, us in medicine, if we're, if our mission is to improve quality of life and decreased burden of disease on people's lives. We have to think outside just, you know, our biochemical tests. I think, you know, I've just learned that we can't afford to operate in our silos, right? The scientists cannot afford to operate and, 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 if we're really going to make progress for elimination and for really alleviating the suffering of hip beyond people's lives. Thank you so much, Dr. Wong, for sharing your story. Thank you. Hi, I'm Erin Welsh. And I'm Aaron Allman Updike. And this is, this podcast will kill you. Welcome to another episode. 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 be 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 that we can cover all in one. It's quite possible. Well, Erin, what time is it? It's quarantine time, Erin. 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 quarantini 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 would 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 a bookshop.org affiliate account and a good reads list. You can find all the sources 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 was 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 like little thoughts of endo that pop in. And I realized that there was like one more thing that I wanted to say. Also like 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's 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 as 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. All right. 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. Dinner shows up every night, whether you're

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That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these, quote-unquote, fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies.

100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious. These are foods that you would want to eat. Not that the babies would ever share. Just Food for Dogs is the number one bet recommended fresh dog food back by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full broadwomened. performance every single night. So I do care about the food I feed big and smalls. So go to

Just Food for Dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food. 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 hepatiti 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, A, B, C, D, 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 Hepadnaviridae, which essentially just means viruses that affect the liver. Like, no surprise. Straightforward. One thing that's, there's a lot of interesting things about the virology 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-sterectus. stranded DNA virus, which is weird. Mm-hmm. 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, Erin? I can see it on your face? I mean, yes, but I'm waiting.

Okay. I'm being patient. Okay. We'll 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. genotypes kind of have different tendencies or characteristics, and some said it's up for debate. So, 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 parankama of the liver.

It's the 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 blood-borne virus. So anything that involves the sharing of blood, whether that's contaminated needles, in the health care 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.

Whoa. So do we know the reasons for that increased infectivity? Oh, that's a very good question. I do not. Okay. Yeah. And I don't also have. have numbers on like 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 hardy virus. So that might be part of it. Yeah. Interesting. Okay. So going back real quick to partially double stranded, what's what's the implication of that in like a virology sense? So it's really interesting. Hepatitis B is one of the few viruses that's not an arreesome. 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 Hep 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 papers 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 hepatinaviruses that do. Right. Okay. So that's like the unifying feature of hepatinaviruses. 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, it's when 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 transplacental. 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.

So 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, and 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. Hmm. 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 transplicentally. 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, you know, 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. 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 bilirubin from our bodies. And so without that process, bilirubin, 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 buildup of not just bilirubin, 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 bilirubin 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. The likelihood of the likely of the

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%. Over 90%. So that means that almost all babies that become infected at birth or shortly thereafter go on to have a chronic lifelong 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 plateau.

What do you call it? No, it's a j-whoop, what a j-o-k, maybe? What do you call it? Sigmoid? A j? So let me just tell you numbers, because I'm clearly not doing a good job. Shwooping. 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 a adult. adults, if you don't get infected until you are an adult, the risk of chronic infection is only about 2 to 5 percent. So substantially lower. Hmm. I mean, okay, I have to ask why. I'm 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 is, 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? But much more people who get infected as adults with hep C go on to get chronic hep 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, while 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 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, Aaron? 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 called 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. Okay. Yeah.

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. Okay. But there is another phase, just to get more complicated. And that's a so-called inactive phase, wherein 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 immunology of hep B 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 establish 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 phases of disease. Right. Okay. Interesting.

But that is generally hepatitis B virus. So I have a question. Mm-hmm. 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 now have a lifetime immunity to hepatitis B virus. What about different genotypes?

Is 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 hep, hep 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 its.

itself. It relies on the surface proteins of hepatitis B virus in order to get into ourselves and in order to be released from ourselves. So hepatitis D is a virus that can only infect someone who has a chronic or acute hepatitis B infection. I am 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 B combined? Yes, for Hepitis B, there are. So there's a number of different treatments that we have actually. None of them can cure hepatitis B. They are all used to sort of manage it and to try and reduce the rate of inflammation and complications. But pegillated 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. used to treat HIV or were 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 help to 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 vary 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 make sense? Yeah, that's interesting. At least as of now, because the treatments that we do have are not without side 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, Erin, like what? 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. Anyone who works long hours knows the routine. wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking.

It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefe. Just visit O'Keefscompan.com slash this podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies.

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So go to Just Food for Dogs. for 50% off your first box, no code, no gimmicks, just real fresh food. Janice Torres here. And I'm Austin Hankwitz. We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio, in partnership with Intuit QuickBooks. And we are back for season four. We're talking to small business owners who are doing incredible things in their industries,

achieving their dreams, being their own bosses, putting in the work, and enjoying all the benefits that come with it. This is our most exciting season yet. We're talking to more entrepreneurs about how they launched their vision, and more importantly, how QuickBooks on the Intuit platform helps them do more in less time. Working in QuickBooks just makes it easier to run the business, right? There's so much that you need to do when it comes to running a business, building products, setting up marketing campaigns.

And to run a business, you have to make sure that your finances are in order. So it removes my anxiety from one side of it so that I can focus. focus on everything else. Whether you're a long-time listener or just getting started, tune in and join us. You'll be so glad you did. Listen on the IHeart Radio app,

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Yesterday we were hiking and kayaking. Today, I'm watching for humpback whales. Anyway, wish you were here. Award-winning Kid-Free Alaskan Cruises from Virgin Voyages with immersive shore excursions and zero kid energy. Virgin Voyages.com. 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 to be. 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 Locarnini at all and the other by a cocher at all. Like you said, Aaron, the hepatitis B virus belongs to the Hepadnevirae 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, and amphibians, other mammals, non-human primates, etc. Basically, this is a lot bigger and a lot older of a virus family than we thought. 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. 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, Erin. 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. 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. universities with all of these remains, skeletal remains. So, okay.

Anyway, so what this paper using all of these old skeletal 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 its spread happened before the Neolithic Revolution, which is when people began settling in larger groups and farming and so forth. on. And if you think about it, this completely makes sense. Because what are some of the transmission characteristics that hepatitis B has, right? 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.

Yeah. 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 7,000 to 8,000 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, Aaron. 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 routes 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 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 and 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. Yeah.

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. We'll toss in the Hippocratic texts from around 400 BCE because it's an episode of this podcast will kill you. We must do that. 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 C.E.

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. it's tricky because of the existence of other hepatitis viruses. Hepatidi. Hepatiti. 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. Right. 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, you know, war. Yeah. And especially in any that were like acute infections. Yes. Right. Like, mm-hmm, exactly. Yeah. 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. So 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 shipworkers 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.

Right. But the link between the administration of this vaccine and the resulting hepatitis outbreak, it wasn't recognized for decades, possibly obscured by this law. long-standing 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 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 hepatitises, 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 U.S. 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, people came down with hepatitis, although those were just the clinically recognized cases. 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. It's a lot. Yeah. And there was a British doctor named F. O. McCallum, 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 blood-borne 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 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. 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 have. Epiditi 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's, then it becomes much easier to add to the list. 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 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 blood-borne 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, 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. It was 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 virology 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, 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 right but I don't but I don't

know it I am like I know it but I can't know it. Mm-hmm. And we can also blame the virus itself because this isn't to say that virology 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. Yeah. And hepatitis B virus doesn't really lend itself very well to culturing in a lab setting.

And so it was just more difficult. And 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. We already said 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 Willabrook 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, Erin. I know. 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 in 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 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, a vaccine could be developed and tested. Parenthood 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's studies reduced 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 Willabrook Hepatitis studies is that the resulting outrage led to very strict regulations placed on, including children in clinical trials and medical studies, and a more revamping of what could be considered medical consent. There's a lot more, of course, like I said, to these studies and they're placed 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 in 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. 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. Yeah. It's especially because B happens to be the first hepatitis virus discovered. Yeah. Okay.

I saw that on a timeline and I was like, whoa, whoa, whoa, hold on. I was like, why is it called B then? Yeah. It doesn't make any sense. 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, in 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? Me too. Cool. Blood types.

What blood type are you? I'm O positive. I'm A, B. 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 bet he found some proteins all right. He certainly did.

But how did he find these proteins? Yeah, I don't know. 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 use the blood of someone who had received multiple transfusions to find antibodies against a protein, antigen, that was new to them. And then you test 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 like super inexpensive

genomic sequencing. But back then, these were the early, early years of genetics. I mean, we still do that to do like regular blood typing. Yeah. So it's like still very useful. So it is, it is super useful. but the approach, like the technology that he used, which was agger gel diffusion, it was basically like one of the only ones available at the time.

Immunology was in its infancy. 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 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 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, pretty 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, rash, etc., after receiving a transfusion. 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 surprise, spoilers, it turned out to be. But in any case, the name Australia antigen, it 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 U.S. 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 trait, but as more data came in, that assumption kind of broke down. Oh, yeah. 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 blood-borne, 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.

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. By 1965 or so, they had become convinced that they had finally found the long sought-after hepatitis B virus, almost by accident. Wow. I mean, truly by accident, really.

Yeah. And they sent off a couple of papers to be published. One was outright rejected with a reviewer comment. 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've found the hepatitis B virus. I found it. It's this. It's this. Kind of like how I feel like every few months now, there's an article saying, the Zodiac Killer has finally been identified. It's like, okay. If we dig a little deeper, like, is it true or is it 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 a 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. And, 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 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 Cook's postulates. difficult. And the test for determining whether or not the virus was present, you're pretty insensitive at the time. Like, I've seen estimates of 15 to 20 percent 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, a lot better. Like, very good. Like, excellent. 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, it didn't start for a few years after the virus was discovered. So in 1970, the hepatitis B virus test became official in the U.S., 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. They 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 the scoffice. 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. 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 faced 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 U.S.

widespread by the FDA. And then 1986, it was updated to not have any like human parts in it, essentially. 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. Do you know who helped work on the yeast aspect? of it? Tell me who, Aaron. Maurice Hilliman, our friend. Oh, let's hear it for Maurice. Let's hear it for Maurice. And I already mentioned one person in this story who was the recipient of a Nobel Prize for their work on hepatitis viruses. And that was in 2020. But in 1976, Dr. Baruch-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 Gajusik. Do you remember him from Priyons, the bad guy? Oh, yes, I do. Uh-huh. 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, hepatitis B research, the virus is still extraordinarily prevalent and transmission continues today. So, Erin, 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 fill me in? Oh, I can't wait too right after this break. Unlike 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? What's the incidence? 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 hepatiti or viral hepatitis is, 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 air in math, just kidding, just kidding, the World Health Organization did this math. That is 820,000 humans that are dying from chronic hepatitis B infection every single year. Now, you asked why we're not. 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. It's, 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,

was 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 20, 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. 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. I know. And still, like, just under 1%, 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 90%. 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. 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 80, 7% of infants worldwide received the three-dose Hep 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 IVI

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 Hep 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 then treatment.

1%? Yeah, 1% or less. 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, like 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 episode, 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. 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 difference is 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 at one book in particular, and that is, of course, Hepatitis B, The Hunt for a Killer Virus by Dr. Brooke Bloomberg. 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. So 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.com.

We sure will. A 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. 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.

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