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

Episode Transcript
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Speaker 1 (00:02):
My name is su Wang. I am a physician. I'm
an MD MPH. I'm the medical director for the Center
for Asian Health and Viral 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,

(00:24):
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,

(00:46):
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 med student, but honestly I didn't know anything about
hep BEE. I called my sister, confided in her about

(01:09):
this new diagnosis, and she said, oh, didn't you know
Mom also has hep BE. 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 back burner. Didn't want

(01:31):
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 heppy vaccination and statuses. And
I had indicated that I was a carrier and didn't

(01:53):
hear anything about it. I didn't think anything of it.

Speaker 2 (01:55):
And it's not untill now.

Speaker 1 (01:56):
That I've heard numerous people who are in med school
found out to have happy and actually they lose their
acceptances to med school or they faced quite a bit
of what I would consider discrimination over their status.

Speaker 3 (02:09):
Uh.

Speaker 1 (02:09):
And it's happened to residents, it's happened to nurses, it's
happened to deal 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 is kind of listening a little bit more attentively.
And when I got to residency after med school, I

(02:29):
became really good friends with somebody. A friend of mine
went into infectious disease, and I had confided in her
that I had happatitis 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.

(02:50):
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 to 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

(03:11):
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

(03:32):
unable to pursue the career they went to.

Speaker 3 (03:35):
So I didn't have.

Speaker 1 (03:36):
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 chants

(03:59):
of the developing hep BE. 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 heap BE free
and that they don't have to live with this chronic
disease and worry about risk of lover cancer and other
things that other kids have to go through even now
in this day and age. And so as a physician,

(04:19):
I didn't particularly have an 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 HEPBE

(04:40):
than I ever knew. That it's, you know, one of
the most common infectious diseases around the world. Up to
like one in ten of our patients had heppy 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 they weren't necessarily
easily accessible. So many of us at the community health

(05:01):
center learned to treat hep BEE 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 be
to increase screening in the communities, linkage to care, all

(05:21):
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 the science behind it.

(05:42):
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 did
an 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

(06:03):
if I was counseling a patient who had been newly
diagnosed with HEPPY and I could see they were really
distraught or felt really overwhelmed, I would share with them
that I also was living with hep BEE. 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,

(06:23):
but I'd 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

(06:44):
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 Whippo region, the Western Pacific region. He
told me all these stories of people who really had
happy drastically empire their life in ways that us in
medicine don't measure.

Speaker 3 (07:04):
Right.

Speaker 1 (07:04):
We measure the outcomes. We look at our morbidity, mortality,
life expectancy right soorrhosis, lever 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

(07:25):
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

(07:48):
of what it means for them to live with a disease.
And so you know, it's beyond just like keeping them
from getting sorosis and liver cancer. You know, us in medicine,
if we're if our mission is to prove quality of
life and decrease burden of disease on people's lives, we
have to think outside just you know, our our biochemical tests.

(08:09):
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 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

(08:30):
concert with the medical community if we're really going to
make progress for elimination and for uh you know, really
alleviating the suffering of be on people's lives.

Speaker 2 (09:23):
Thank you so much, doctor Wong for sharing your story.
Thank you. Hi. I'm Aaron Welsh and.

Speaker 3 (09:30):
I'm Aaron Alman Updyke.

Speaker 2 (09:32):
And this is this podcast will Kill You.

Speaker 3 (09:36):
Welcome to another episode.

Speaker 2 (09:38):
Yes, welcome, Welcome. As you have probably gathered, we are
going to be talking about another hepatitis virus, our second
podcast history. Yes, this one hepatitis B. Yeah, we started
with C. Now we're going to be what's next? Uh, well,
I am going to mention D. I figured.

Speaker 3 (10:03):
I think next will be A.

Speaker 2 (10:05):
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.

Speaker 3 (10:11):
More and we can cover all in one quite possible.

Speaker 2 (10:15):
Well, Aaron, what time is it?

Speaker 3 (10:19):
It's quarantiny time, Aaron.

Speaker 2 (10:21):
It is. And what are we drinking this week?

Speaker 3 (10:24):
We're drinking the beasting.

Speaker 2 (10:27):
We are appatitis B, hepatitis B. And what is in
the beasting?

Speaker 3 (10:33):
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.

Speaker 2 (10:44):
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 Placey Brita on our
website This podcast Willkill You dot com, as well as

(11:05):
on all of our social media channels.

Speaker 3 (11:07):
On our website This Podcast will Kill You dot 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 dot org affiliate account, and

(11:32):
a good Reads list. You can find all You're doing
great things for all of our episodes.

Speaker 2 (11:36):
Thanks.

Speaker 3 (11:37):
I need the encouragement, and you can find our Patreon.

Speaker 2 (11:41):
Wow, that was impressive. Thank you.

Speaker 3 (11:45):
Thanks.

Speaker 2 (11:46):
I'm always relieved when I don't have to do it.

Speaker 3 (11:49):
I always get really nervous and then I just power through.

Speaker 2 (11:52):
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 happatitis B,
I still have these like little thoughts of endo that

(12:15):
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

(12:35):
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,

(12:57):
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

(13:19):
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 more important than what they want than
their wishes.

Speaker 3 (13:35):
Yeah.

Speaker 2 (13:36):
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.

Speaker 3 (13:45):
Yeah, that's an incredibly important point.

Speaker 2 (13:49):
Okay, should we move on to the actual topic of
today's episode.

Speaker 3 (13:54):
Today's topic hepatitis B. Let's take a quick break and
then get into the biology. So, like you mentioned erin,

(14:35):
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

(14:57):
all predominantly affect the liver. 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

(15:19):
between hepatitis D and B. All right, hepatitis B. It's
in the family Hepadnavii day, 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

(15:40):
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.

(16:00):
Do you have a question already?

Speaker 2 (16:01):
Erin I can see, I mean yes, but I'm waiting,
being patient.

Speaker 3 (16:06):
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.

Speaker 2 (16:27):
Virus, like incredibly incredibly prevalent.

Speaker 3 (16:33):
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.

(16:53):
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 hepatocites,
our actual liver cells, not the blood vessels in our liver,
not any of the other things around there, but generally

(17:15):
our liver cells.

Speaker 2 (17:17):
The things that make up the meat.

Speaker 3 (17:19):
Of the liver exactly, also called the paranama of the liver,
the fancy word for.

Speaker 2 (17:26):
The meat.

Speaker 3 (17:29):
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 born virus, So anything that involves the
sharing of blood, whether that's contaminated needles in the healthcare

(17:51):
setting or in intravenous drug use settings, it can be
transmitted via blood transfusions, and of course is something that
we see screen for to try and reduce the.

Speaker 2 (18:01):
Risk of that.

Speaker 3 (18:03):
But hepatitis B is also much more easily transmitted sexually
compared to hepatitis C. It's present in so many bodily fluids.

Speaker 2 (18:13):
Why is that?

Speaker 3 (18:15):
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 fifty to one hundred times more
infectious than HIV WHOA.

Speaker 2 (18:33):
So I know, do we know the reasons for that
increased infectivity.

Speaker 3 (18:39):
Oh, that's a very good question. I do not, Okay, yeah,
And I don't also 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.

Speaker 2 (18:59):
Yeah, Okay, So going back real quick, partially double stranded,
what's the implication of that in like a virology sense?

Speaker 3 (19:09):
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

(19:29):
then replicate, and B also does even though it's a
DNA virus.

Speaker 2 (19:36):
That is so bizarre, and so I definitely came across
some of that in the evolution behabers because it kind
of throws a wrench in things as to like the
mutation rates, the scale of the molecular clock, blah blah blahh.

Speaker 3 (19:48):
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.

Speaker 2 (20:03):
Aha, spoilers do other viruses have this partially double stranded
DNA thing as well.

Speaker 3 (20:14):
I don't know of any other human viruses, but I
know that there are other animal hepatnaviruses that do.

Speaker 2 (20:19):
Right, Okay, those so that's like the unifying future of hepatnaviruses.

Speaker 3 (20:24):
Okay, yeah, yeah, wow cool? Okay, So hepatitis B is
also transmitted back to that part of it vertically at
much higher rates.

Speaker 2 (20:36):
This.

Speaker 3 (20:37):
Let me tell you some numbers. The estimates that I
read ranged from forty to ninety percent of babies born
to people living with hepatitis B with chronic hepatitis B
will become infected with hepatitis if they are not treated.

Speaker 2 (20:53):
Wow.

Speaker 3 (20:54):
And this is in comparison to only six percent of
people with hepatitis C will then transmit hepatitis C to
their offspring.

Speaker 2 (21:03):
What is the reason for that difference?

Speaker 3 (21:06):
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 transmissions,
so from parent to offspring, it's wind viruses or bacteria

(21:27):
can cross the placenta and infective 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.

(21:50):
It's happening specifically during the period of childbirth, whether that
birth happens vaginally or VC 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

(22:13):
sense because neither one is really less bloody than the other,
and so many bodily fluids are being exchanged no matter
what exit root a baby takes.

Speaker 2 (22:22):
It's so it's just like the blood and bodily fluids.

Speaker 3 (22:25):
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. 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 transpolacentally.

(22:47):
Yet it's not, and that is really important when we
talk about how to treat and prevent hepatitis B infection.

Speaker 2 (22:55):
So let me.

Speaker 3 (22:56):
Keep going, shall I? You shall The incubation period of infection,
the time from when someone gets infected to when they
show symptoms, can really range anywhere from thirty days to
up to six months. And I think that this incubation period,
even noting it incubation period, is interesting because hepatitis B

(23:21):
is a virus that can be entirely asymptomatic, and chronic
infection is generally defined as the persistence of a specific
anigen being able to detect hepatitis b's surface antigen for
a period of at least six months. So it's interesting
that you can also say the incubation period itself might

(23:42):
be six months before you show symptoms, but you also
might never show symptoms.

Speaker 2 (23:47):
Yeah. Yeah, that makes it really difficult to calculate an
incubation exactly. It sure does.

Speaker 3 (23:56):
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

(24:18):
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

(24:39):
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 that become yellowish.

(25:02):
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,

(25:25):
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

(25:47):
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,

(26:08):
but much more commonly, liver failure happens as a progressive
process of long term inflammation, leading to cirrhosis and fibrosis
and potentially hepatocellular carcinoma or cancer. So I want to
focus on this, this chronic infection of hepatitis B, because

(26:33):
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

(26:53):
become exposed and infected. So for infants, for neonates who
get infected vertically during birth, the likelihood of a chronic
infection is over ninety percent over ninety percent, So that
means that almost all babies that become infected at birth

(27:16):
or shortly thereafter go on to have a chronic lifelong
infection with a very significant risk of progression to fibrosis
and or liver cancer.

Speaker 2 (27:28):
So this inverse relationship, is it like a straight line
or does it kind of have any sort of peaks
and valleys.

Speaker 3 (27:35):
It's not a straight line, it's a it's a well,
what do you call it? No, it's a what a zoop? Maybe?

Speaker 2 (27:44):
What do you call it? Sigmore a jay?

Speaker 3 (27:46):
So let me just tell you numbers, because I'm clearly
not doing a good job swooping. So infant neonate ninety
percent chance a child if they get in afected when
they're young, like between ages one to five, the risk
of chronic infection is like thirty percent. So it's a
pretty big drop, and then it's a little lower for

(28:09):
older children and for adults. If you don't get infected
until you are an adult, the risk of chronic infection
is only about two to five percent, so substantially lower.

Speaker 2 (28:21):
Hmm. I mean, okay, I have to ask why.

Speaker 3 (28:25):
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 itself and the like prognosis
of a chronic infection with hepatitis B in general is

(28:47):
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

(29:07):
rate of for example, liver cancer is very low, like
two point five percent for people who have chronic hepatitis C. Right,
But much more people who get infected as adults with
HEPSI go on to get chronic HEPSI.

Speaker 2 (29:22):
That makes sense, yeah, Like, okay, in the numbers, perspective, right, But.

Speaker 3 (29:28):
For hepatitis B, fifteen to forty percent of people who
have chronic infection go on to have liver cancer, hepatocellular carcinoma.
It's a huge percentage.

Speaker 2 (29:43):
Yeah.

Speaker 3 (29:43):
And again, ninety percent of infants who become infected go
on to have chronic infection. So that's major.

Speaker 2 (29:53):
That's a really disturbingly large number, right.

Speaker 3 (29:57):
Okay, So you asked why, Yeah, I did. In short,
we don't fully know. It's always my answer.

Speaker 2 (30:09):
I'm going to cross stitch that onto a pillow for you.

Speaker 3 (30:12):
I would love that pillow.

Speaker 4 (30:14):
Oh my gosh.

Speaker 3 (30:16):
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

(30:38):
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

(30:59):
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 er

(31:20):
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

(31:43):
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, This
is the phase where people are more likely to be symptomatic,
like maybe have jaundice. But this is the phase where

(32:07):
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

(32:28):
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

(32:49):
could still revert back to a more immune active infection,
like say if they became immuno compromised for some reason
and therefore the virus is still there and still posing
risk of cancer development.

Speaker 2 (33:02):
Gotcha that makes sense.

Speaker 3 (33:04):
Yeah, So I know that that was a lot and
it was really just a drive by. The immunology of
HEPBIE 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

(33:27):
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

(33:51):
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 entire the way most
adults who are exposed can, they instead establish this relationship
of tolerance that lends itself more easily to a chronic infection.

Speaker 2 (34:10):
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.

Speaker 3 (34:20):
But then eventually progress to the other phases of disease.

Speaker 2 (34:24):
Right, okay.

Speaker 3 (34:25):
Interesting, but that is generally hepatitis B virus.

Speaker 2 (34:30):
So I have a question, h 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 are is there any

(34:53):
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?

Speaker 3 (35:03):
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

(35:28):
of hepatitis B, and that is what we make antibodies too.

Speaker 4 (35:32):
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?

Speaker 3 (35:46):
Not as far as I know, But do you know what?
They can become infected.

Speaker 2 (35:50):
With hepatitis D.

Speaker 3 (35:52):
Hepatitis D. Thanks for the little intro there.

Speaker 2 (35:57):
You're welcome. You're welcome.

Speaker 3 (35:59):
I want to just very we 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 HEPD, it's a
fascinating virus. This virus belongs to its entire own viral

(36:19):
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 subviral agent.

Speaker 2 (36:32):
Whoa what it's like a virus of a virus.

Speaker 3 (36:36):
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

(36:56):
by itself. It relies on the surface pines 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.

Speaker 2 (37:20):
I'm really regretting right now not reading more about the
evolutionary origins of hepatitis D because.

Speaker 3 (37:27):
On Earth, maybe it does deserve its whole own episode. Yeah,
that's that's literally all I have to say about it.
But it is very very interesting.

Speaker 2 (37:38):
Okay, So what about besides the vaccine? What about treatments?
Are there anti viral treatments for hepatitis B virus or
maybe B and hept combined.

Speaker 3 (37:48):
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 are all used to sort
of man and to try and reduce the rate of
inflammation and complications. But pigilated interferon, which I think we
talked about in our hepsy episode, possibly, but that's basically

(38:12):
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 anti
virals that in many cases are used to treat HIV
or we're used to treat HIV and are now used
to treat he B. So yes, there are Again, none

(38:34):
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 very person to person and how

(38:54):
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?

Speaker 2 (39:10):
Okay? Yeah, that's interesting.

Speaker 3 (39:12):
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 that I know,
so speaking of so much about this virus arin like

(39:35):
what where did it come from? What the heck?

Speaker 2 (39:39):
I will do my best to answer those questions, But
let's take a quick break first, all right, the story

(40:19):
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

(40:42):
of its identification, and then finally getting us to where
we are today.

Speaker 3 (40:48):
The usual, the usually, I love it, but usual.

Speaker 2 (40:51):
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

(41:13):
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

(41:35):
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

(41:57):
in twenty twenty one about the origins evolution of the
hepatitis B virus, one by Lochernini at all and the
other Bycolture at All. Like you said, Erin, the hepatitis
B virus belongs to the Hepadinaviidae family, and in the
years after the hepatitis B virus was first identified, researchers

(42:18):
found viruses belonging to that family that infected birds, fish, reptiles,
and amphibians, other mammals, non human primates, et cetera. 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 eighty two million

(42:39):
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, eighty two million years let's stick with that. Yeah,
So from eighty two million years years ago, how did

(43:01):
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

(43:21):
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 twenty twenty one used hepatitis
B virus detected in skeletal remains of one hundred and

(43:43):
thirty seven individuals found in Eurasia and the Americas and
dating between ten thousand, five hundred years ago and four
hundred years ago. What that's some old viral DNA.

Speaker 3 (43:58):
I just love it when you find things like this, Aaron,
I know.

Speaker 2 (44:02):
It's this paper was really interesting. It also had the
most authors of any paper I've ever seen. I think
it was one hundred and seventy something.

Speaker 3 (44:10):
Oh my goodness, that's more than like the whole human
genome paper.

Speaker 2 (44:18):
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 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.

(44:43):
And what they propose is that the most recent common
ancestor of the hepatitis B virus dates back to around
twelve thousand to sixteen thousand years ago, which is more
recent actually than was previously thought. And it places that
most recent common ancestor in your Asia, where over the
next hundreds and thousands of years it spread across Eurasia,

(45:06):
into Africa, through Europe and to the Americas. It seems
like the emergence of the hepatitis B virus and some
of it spread happened to 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

(45:28):
characteristics that hepatitis BEE 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

(45:49):
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 pupeat.
So in that way, it's a lot like a couple
of the other viruses that we've talked about before, like
the herpee simplex virus or chicken pox virus. But once

(46:11):
people began settling in larger groups around seven thousand to
eight thousand 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

(46:34):
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 four thousand years, but then
it disappeared around thirty three hundred years ago. It just

(46:55):
went almost extinct. No idea why, Maybe sampling bias, maybe
a reduction in human population that kind of like bottlenecked
or eliminated it, or maybe it was like inter genotype dynamics.
Who knows? So interesting eron, I find this so fascinating,
and this pattern of genotypes going extinct and shifts in

(47:18):
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

(47:40):
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

(48:02):
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

(48:24):
kind of like persisted in human populations for all of
that time. But were the people who were around back
then aware of this? Did they have any idea?

Speaker 3 (48:37):
Were they did?

Speaker 2 (48:38):
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 an ancient medical text.
I'll toss in the Hippocratic texts from around four hundred
BCE because it's an episode of this podcast will Kill

(48:59):
You and 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 eighth century CE, and it was sometimes called campaign
jaundice because it seemed prevalent during times of war. Surprise, surprise,

(49:22):
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 hepatiti hepatid.
We can test human remains for hepatitis B virus, specifically

(49:43):
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 f may have been the culprit more often than not,

(50:03):
especially in crowded or unsanitary conditions like you know, war.

Speaker 3 (50:08):
Yeah, and especially in any that were like acute infections.

Speaker 2 (50:14):
Yes, like mm hm, exactly, yeah. But it's certainly possible
that hepatitis BE 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 nineteenth century. So let's fast forward to then the

(50:38):
last decades of the eighteen hundreds. So this is like
after the development of germ theory and after the introduction
of some injectable vaccines. In eighteen eighty five, an epidemic
of jaundice followed a smallpox vaccination campaign among shipworkers in Bremen, Germany,
which led to what seems like an early indication that

(51:01):
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

(51:26):
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 to

(51:46):
the same watering hole where they all got hepatitis.

Speaker 3 (51:50):
Yeah.

Speaker 2 (51:51):
Yeah. But as blood transfusions increased and the practice of
reusing needles persisted, there was this growing suspicion that an
in 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

(52:12):
system and so on. 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 nineteen forties. During World War Two, hundreds
of thousands of US Army personnel received the yellow fever vaccine, which,

(52:37):
like the eighteen eighty five 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,
fifty thousand people came down with hepatitis, although those were

(52:57):
just the clinically recognized cases. Later estimates put the total
figure of hepatitis infections resulting from this vaccination campaign at
around three hundred and thirty thousand.

Speaker 3 (53:10):
Oh dear, okay, oh gosh, Oh dear, okay.

Speaker 2 (53:14):
It's a lot, it's a lot. Yeah. And there was
a British doctor named f. O. Mcallum 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 born infection, separate from

(53:37):
the previously recognized food and waterborn hepatitis. He proposed that
they be called hepatitis A and B, and that they
may represent different viruses.

Speaker 3 (53:50):
So this is how it begins.

Speaker 2 (53:52):
This is how it begins because at the time it
was like not known whether it was the 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

(54:14):
water or whatever, other researchers began to describe differences in
the way that these two hepatida looked clinically, and to
kind of keep an eye out more on the different
roots of transmission.

Speaker 3 (54:29):
Once you have it more like hey, there are two
different things here, then you start to notice more of
the differences.

Speaker 2 (54:35):
Right. Once you create those like columns, then it's then
it becomes much easier to add to the listen in.
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. Liked I talked

(54:56):
about in our hepatitis see 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 it was like, well, we don't

(55:18):
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 was no option. That's
not to say that people weren't working on finding a

(55:39):
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
bee agent was so that they could detect it in
blood products. But despite a ton of people work looking

(56:00):
on this, progress kind of stalled in the nineteen fifties
and early nineteen sixties. 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.

Speaker 3 (56:20):
I'm sorry, I just I had I don't know how
I didn't know that it was so recent. I know,
like nineteen fifties, nineteen sixties, that's not a long time ago.

Speaker 2 (56:36):
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

(56:57):
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.

Speaker 3 (57:03):
Right, But I don't but I don't know it. I
am like, I know it, but I.

Speaker 2 (57:08):
Can't know it. Mm hm. 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 nineteen fifties or sixties, 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

(57:29):
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?

Speaker 3 (57:40):
Yeah, and it's a weird virus. We already said that, Yeah,
it's a weird, very weird.

Speaker 2 (57:45):
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 nineteen sixties that would change,
and the team that led to the breakthrough identification of

(58:09):
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.

Speaker 3 (58:18):
Why who was it?

Speaker 2 (58:21):
Okay, I'll get there, But before we get into the
unlikely story of the discovery of the HEPB 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

(58:42):
be brief because these studies are mostly about hepatitis A,
and so when we do a HEPA 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 nineteen

(59:05):
forty seven on Staten Island, New York, for children who
were intellectually or developmentally disabled.

Speaker 3 (59:12):
I hate this already, erin.

Speaker 2 (59:13):
I know, I know, I know. In nineteen fifty eight,
infectious disease physician doctor Saul Krugman from New York University
in 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 thirty to
fifty percent admitted there would end up getting hepatitis, and

(59:35):
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

(59:57):
persons protected by gamma globulin, and to describe the excretion
of virus during the incubation period of the disease. Dear,
your face tells me you've picked up on some of
the yeah problems with these studies intentionally infecting children. So
Krugman justified the research by saying that the children would

(01:00:20):
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. 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's studies reduced the

(01:00:42):
incidence of hepatitis by eighty five percent. 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 HEPB vaccine which did
seem to be somewhat effective. The legacy of the Wiliberg

(01:01:05):
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 their place in the
history of medical ethics. And so if you're interested in

(01:01:28):
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 nineteen eighty six 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

(01:01:50):
didn't do it justice, so let me just say that, Wow, yeah, okay, okay,
back to strictly hepatitis B. So, by the nineteen sixties,
the hepatitis B virus had still not been identified, despite
the fact that tons of people were working on this problem.

(01:02:12):
And when it was finally discovered, it wasn't by one
of those researchers who had dedicated their lives to hepatitis,
but by a team who had not even been looking
for hepatitis B or any other virus.

Speaker 3 (01:02:27):
What were they looking for?

Speaker 2 (01:02:31):
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 two C it's especially because
B happens to be the first hepatitis virus discovered.

Speaker 3 (01:02:47):
Yeah, Okay, I saw that on a timeline and I
was like, well, well we'll hold on, hold on, hold on.

Speaker 2 (01:02:51):
I don't know. It was like, why is it called B?

Speaker 3 (01:02:53):
Then yeah, it doesn't make any sense.

Speaker 2 (01:02:57):
Yep, everything's just arbitrary. 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

(01:03:19):
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 doctor Baruch Bloomberg.

Speaker 3 (01:03:44):
Okay, Hi.

Speaker 2 (01:03:47):
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.
Basic and he became interested specifically in polymorphisms. So these
are genetic traits for which there are multiple forms. So

(01:04:10):
things like tongue twisting, Can you twist your tongue?

Speaker 3 (01:04:13):
Yes?

Speaker 2 (01:04:14):
Can you too?

Speaker 1 (01:04:15):
Cool?

Speaker 2 (01:04:16):
Blood types, what blood type are you?

Speaker 3 (01:04:18):
I'm oh positive, I'm ab positive. I knew that about you.

Speaker 2 (01:04:22):
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

(01:04:43):
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 pro teen polymorphisms that could be associated

(01:05:03):
with variation in disease susceptibility. So that's what he was
looking for.

Speaker 3 (01:05:07):
He wasn't even looking for virus.

Speaker 2 (01:05:09):
No, he was looking for blood plasma protein polymorphisms.

Speaker 3 (01:05:13):
Wow, I bet he found some proteins, all right.

Speaker 2 (01:05:17):
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
use the blood of someone who had received multiple transfusions

(01:05:40):
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 protein today in the days

(01:06:01):
of like you know, super inexpensive genomic sequencing, but back then,
these were the early early years of genetics.

Speaker 3 (01:06:09):
I mean, we still do that to do like regular
blood typing. Yeah, so it was like still very useful.

Speaker 2 (01:06:16):
It so it is, it is super useful. But the approach,
like the technology that he used, which was Agargell 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.

(01:06:40):
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

(01:07:02):
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 former hepatitis
C episode. Except when I looked through my notes for

(01:07:23):
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.

Speaker 3 (01:07:39):
I bet you talked about a lot of important things, aren.

Speaker 2 (01:07:42):
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 twenty twenty he was awarded the Nobel Prize
for his role in hepatitis C research. Ohtty cool?

Speaker 3 (01:07:56):
Whoa Yeah?

Speaker 2 (01:07:59):
So anyway, Alter, who was in the beginning of his
career in the early nineteen sixties, he was interested in
why some people developed an immune response like a fever, chills, rash, etc.
After receiving a transfusion. Yeah, interesting, sef And it took
a little bit of time, little trial and error, but

(01:08:20):
alter In 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

(01:08:40):
out that at the time, this Australia antigen was just
thought to be a human protein, not necessarily an actual pathogen,
which surprised 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.

Speaker 3 (01:09:04):
I love this story.

Speaker 2 (01:09:05):
I know it's 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
agg protein, which you know, was it more common in

(01:09:27):
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

(01:09:49):
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

(01:10:12):
rather an infectious agent, one that was possibly bloodborn, 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

(01:10:33):
began to find the antigen at high rates and people
who had hepatitis okay, especially those with a history of transfusion.
By nineteen sixty five or so, they had become convinced
that they had finally found the long sought after hepatitis
B virus almost by accident, I mean truly by accident, really,

(01:10:56):
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

(01:11:17):
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 have 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

(01:11:41):
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 be seen. They had
no background and studying hepatitis. None of them had been

(01:12:02):
trained as epidemiologists, let alone virologists, so what do they
know about hepatitis? But despite this initial rejection and the
resentment from some prominent hepatitis researchers, they managed to get
a paper published in nineteen sixty seven that awakened the
world to the possibility that the virus causing transfusion hepatitis,

(01:12:26):
the hepatitis B virus, had finally been found.

Speaker 3 (01:12:29):
Nineteen sixty seven.

Speaker 2 (01:12:32):
Hm. Wow, yeah, and this seems like an understatement, but
this was huge news at the time. Post transfusion hepatitis
rates reached thirty percent.

Speaker 3 (01:12:45):
Oh my.

Speaker 2 (01:12:47):
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

(01:13:09):
it's yeah, but there was still another step, and that
was confirmation from other researchers boom, easily done. Check, here's
hepatitis be the end, almost the end actually, the discovery
of the hepatitis B virus. This allowed not only for

(01:13:32):
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

(01:13:55):
conventional tissue cultures, which made fulfilling Cook's postulis difficult, and
the test for determining whether or not the virus was
present pretty insensitive at the time. Like I've seen estimates
of fifteen to twenty percent of the time it would
detect hepatitis B virus. Yeah, that's pretty bad. It's gotten

(01:14:15):
a lot better. We should point out a lot 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

(01:14:37):
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 nineteen seventy
the hepatitis B virus tests became official in the US,
and in nineteen seventy two the American Association of Blood
Banks had begun to require the testing of donors, though

(01:15:00):
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

(01:15:21):
appatitis B. People were fired from jobs, they were not
allowed in classrooms, children were taken off adoption lists. People
were being denied healthcare 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,

(01:15:42):
we have this test, we can help prevent hepatitis and
also we can put the scarlet letter of hepatitis on
every single person that we test.

Speaker 3 (01:15:52):
I feel like that part of hepatitis B especially is
so overlooked today, hmm, Like yeah, yeah.

Speaker 2 (01:16:03):
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,

(01:16:25):
many people began working on a hepatitis B vaccine, including
Bloomberg and his colleague doctor Irving Millman, who came out
with one in nineteen sixty nine, 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

(01:16:45):
gotten a pretty solid, from my understanding, hepatitis B vaccine.

Speaker 1 (01:16:50):
Yeah.

Speaker 3 (01:16:50):
Since nineteen eighty one was when the hepatitis BA vaccine
was licensed like in the US widespread by the FDA,
and then nineteen eighty six it was updated to not
have any like human parts in it. Essentially it's made
in a yeast and it's a real combinant vaccine, and

(01:17:11):
as far as I know, it's the same vaccine since
nineteen eighty six.

Speaker 2 (01:17:15):
Do you know who helped work on the yeast aspect
of it?

Speaker 3 (01:17:19):
Tell me who erin?

Speaker 2 (01:17:21):
Maurice Hillman are Oh, let's hear it for Maurice. He's
here 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
twenty twenty. But in nineteen seventy six, doctor Brooke Bloomberg
was awarded the Nobel Prize in Physiology or Medicine for

(01:17:44):
his work and identifying the hepatitis B virus.

Speaker 3 (01:17:47):
Love it.

Speaker 2 (01:17:48):
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 Gadgasek. You
remember him from Preon's The Bad Guy. Yes, yes, I do.

Speaker 3 (01:18:05):
Uh huh.

Speaker 2 (01:18:08):
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,

(01:18:34):
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

(01:18:59):
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?

Speaker 3 (01:19:09):
Oh, I can't wait to right after this break. Unlike

(01:19:45):
our first three episodes, I have some a lot of
statistics for this section, Aaron, first three episodes of this season,
I mean, but they're pretty sobering. Okay. Globally, it is
estimated that close to four percent of the entire world's

(01:20:09):
population is living with chronic hepatitis B infection. That is
close to three hundred million human beings. And believe it
or not, that's an improvement because the very first paper
I read was a bit older, from two thousand and four,

(01:20:29):
and that started off by saying over four hundred million people,
So we're down.

Speaker 2 (01:20:36):
So those are people chronically infected.

Speaker 3 (01:20:38):
Right, living with chronic hepatitis being and how.

Speaker 2 (01:20:41):
Many people are infected newly every year?

Speaker 3 (01:20:44):
What's the The World Health Organization estimates one point five
million people are newly infected every year.

Speaker 2 (01:20:52):
Wow.

Speaker 3 (01:20:54):
Yes, it's horrific. If we look at the entire spectrum
or the whole alphabet of hepatida or viral hepatitis is
viral hepatitis caused an estimated one point three four million
deaths in twenty fifteen alone, which is more than HIV.

(01:21:20):
It is substantially more than malaria, and it's nearly as
much as tuberculosis.

Speaker 2 (01:21:26):
So why does it feel like it's not talked about?

Speaker 1 (01:21:30):
Why?

Speaker 3 (01:21:30):
Erin, I don't know, Okay, And that's all of the
viral hepatitis hepatidi Okay. Of all of those deaths, ninety
six percent are estimated to be from chronic hepatitis. And
of that ninety six percent, sixty six percent of those
are from hepatitis B. So if we do some aerin math,

(01:21:54):
just kidding, just kidding, the World Health Organization did this
that that is eight hundred and twenty thousand humans that
are dying from chronic hepatitis B infection every single year.

Speaker 2 (01:22:12):
Ah.

Speaker 3 (01:22:14):
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, you know, divides the globe into different regions.
The Western Pacific region by far has the highest incidents

(01:22:35):
and prevalence of hepatitis BE, followed by the World Health
Organization African region. And in these areas the prevalence can
be as high as six percent or greater in some cases, wow, oh,
whereas in some parts of the world, like in Europe
or in North America, the prevalence may be less than
one percent. And so I think that huge global discrepancy

(01:22:59):
can lead for some countries to not think a lot
or talk a lot about hepatitis B.

Speaker 2 (01:23:05):
Yeah, it's oh, well, it's not a problem here, so.

Speaker 3 (01:23:10):
Exactly, Aaron, I think I wrote those exact words later on. Yeah,
And it gets more sobering because it's also estimated that
only ten percent ten and a half percent of people
that are living with hepatitis B know their status. And

(01:23:32):
it's also estimated that only twenty two percent of those
that are diagnosed that know their status are on treatment
for chronic hepatitis. Be 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

(01:23:53):
not be quite as bad as it sounds. But ten
percent of people knowing their status is pretty bad.

Speaker 2 (01:24:00):
Yeah, that's I mean, that's yeah.

Speaker 3 (01:24:04):
Yeah, it's also I have more numbers as a number
heavy one, and these numbers are from a modeling study
from twenty sixteen data. But of this almost four percent
of the global population that is infected with chronic hepatitis B,

(01:24:26):
between one point six to two point two million are
children under the age of five, and the World Health
Organization most recent data does suggest that it's now finally
just under one percent of all children worldwide under age
five that are chronically infected. That's down from around five

(01:24:46):
percent of all children in the pre vaccine era. Oh
my gosh, I know, and still like just under one percent,
essentially one percent of all kids under age five globally
living with this chronic infection. That I can't emphasize enough

(01:25:06):
is entirely preventable. At this point, we have had a
vaccine for hepatitis B that is ninety eight to one
hundred percent effective for seventeen to thirty years, like not
a lot of waning immunity, incredibly effective vaccine for forty years.

Speaker 2 (01:25:29):
So I have a question about that. So is it
part of every single routine vaccine schedule.

Speaker 3 (01:25:37):
Over one hundred and eighty countries have hepatitis B as
part of their universal vaccine program, and it's estimated that
eighty seven percent of infants worldwide received the three dose
B vaccine series in their first year of life, which
is great, but only forty six percent likely had a

(01:25:59):
timely birth vaccination that critical twelve to twenty four hour window,
and even less, this study estimated about thirteen percent got
both the hepatitis B vaccine and if needed, that IVIG
to actually treat and provide more passive immunity. But with

(01:26:22):
IVIG and the vaccine within twelve to twenty four hours
of birth, it's still about ninety one percent effective to
prevent 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

(01:26:43):
one percent of pregnant people are actually getting that testing
and then treatment one percent. Yeah, one percent or less,
And so that contributes a lot to the overall burden
and why we still have such high infection rates.

Speaker 2 (01:27:02):
We have the tools, just not the delivery.

Speaker 3 (01:27:04):
Yeah, so we have a lot of improvements to still
be made.

Speaker 2 (01:27:09):
Yeah.

Speaker 3 (01:27:10):
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

(01:27:32):
aspects that we didn't fully cover in this episode, especially
the substantial stigma and discrimination faced by so many people
living with hepatitis BE around the world.

Speaker 2 (01:27:42):
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.

Speaker 3 (01:27:54):
Woo oooh, you heard that right, bonus episode.

Speaker 2 (01:27:58):
So I enlisted the help of the amazing doctor 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 doctor Cohen's brain about what it's
like to work in the public health nonprofit world, what

(01:28:18):
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.

Speaker 3 (01:28:29):
And we know there's a lot of you out there.

Speaker 2 (01:28:31):
There's a lot of you out there. Yes, it was
so much fun chatting with doctor Cohen, and you should
definitely mark your calendars so you don't miss the app.
It comes out next Tuesday, February first. Okay, but should
we maybe wrap up this episode for now?

Speaker 3 (01:28:47):
I think we should time for sources.

Speaker 2 (01:28:50):
It is a 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 that one book in particular,
and that is, of course, Hepatitis B The Hunt for
a Killer Virus by doctor Bruke Blumberg.

Speaker 3 (01:29:07):
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 twenty eighteen and
called Chronic Hepatitis B Virus Infection has a lot more
detail about the different phases of chronic infection, and we'll

(01:29:29):
post the sources for this episode and every one of
our episodes on our website. This podcast will kill you
dot com.

Speaker 2 (01:29:35):
We sure will. A big thank you again to doctor
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.

Speaker 3 (01:29:49):
Yeah, thank you so much. Thank you also to Bloodmobile
for providing the music for this episode and all of
our episodes.

Speaker 2 (01:29:56):
And thank you too, exactly right of whom we are
a very proud member.

Speaker 3 (01:30:01):
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.

Speaker 2 (01:30:09):
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

Speaker 3 (01:30:22):
You filthy animals.

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

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Erin Welsh

Erin Allmann Updyke

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.css-14f5ked{margin:0;word-break:break-word;display:-webkit-box;-webkit-box-orient:vertical;box-orient:vertical;-webkit-line-clamp:2;overflow:hidden;}From the Vault - Hepatitis B: Hepatiti, Take 2 (Ep 89)