In two thousand and five, my life changed forever. My mom had just been diagnosed with hepatitis C and advised me to get tested. When my doctor told me I also had it, the room went dark. All my thoughts stopped, and I didn't hear anything else being said. I worried that I'd given my kids a deadly disease. The next day, I scheduled my family to be tested. Everyone's results were negative, but this didn't end my personal nightmare with the disease.
I was witnessing hepatitis C ravaged through my mom's body. A liver transplant would only buy her time. She ultimately chose not to undergo a dual organ transplant and passed away on May sixth, two thousand and six. My liver began to deteriorate quickly. I went from stage one to stage four in less than five years, which terrified me.
I saw no hope. After years of unsuccessful treatments and being unqualified for clinical trials, I was finally accepted for a clinical trial in early twenty thirteen and began the treatment later that year. My viral load started at seventeen million. I went back for a blood draw in three days and it had dropped to seven hundred and twenty five. At day five, I was at one twenty four and in seven days my viral load was undetected. This trial drug had destroyed the very thing that killed my mother
seven years earlier. Today, I've managed a sustained viri logic response for four and a half years, but it's been along road. One thing I always tell people who contact me is that nobody's hepatitis SEA journey is the same. We may have the same symptoms, but how our bodies respond to treatments is unique. Don't hide in shame about having hepatitis SEA. It doesn't matter how you contracted it.
What matters is that we get tested and treated. That was from Kimberly Morgan Bossley and her story with hepatitis C that we found on Healthline. Hi, I'm erin Welsh and I'm erin omen uptake.
And this is this podcast will kill you today.
We're talking about hepatitis C.
As you may have guessed, it's.
Kind of like in the first hand a bunch of times.
Yep, yep. So what are we drinking this week?
We're drinking Live and Let Liver.
And what is in live and let liver.
Well, of course there's alcohol, which is you know, take it easy on the alcohol on this one, guys.
Or just make yourself the plasy Burta that too.
But in the quarantini we have gin, grapefruit juice, lime juice, and grenadine.
Yeah, it's delicious, and we will post the recipe to our alcoholic quarantini as well as our non alcoholic placy Burta on our website This podcast will kill You dot Com and our social media pages so Twitter, tpwkhy, Instagram, this podcast will kill you and Facebook. Yep.
Cool.
Cool. I'm excited for this episode.
I know you are. I know you are, But what am I also excited?
You're such a nerd.
I know. I can't believe that's the first time I've ever said that joke. Actually, that was a good joke.
I was a good joke.
Thank you. Let's take a really short break and then dive in to hepatitis. So hepatitis literally just means inflammation of your liver. Okay, makes sense. So we probably most often at least many of us, think of viral hepatitis when we hear the word hepatitis, But do keep in mind that that's not by any means. The only thing that can cause inflammation of your liver.
What else can cause inflammation of your Oh my gosh, bacteria can cause it. You know that parasites asking me to ask that question.
I know parasites can cause hepatitis. You can have autoimmune hepatitis, you can get like hepatic involvement if you have things like lupus, blah blah blah. It's so many things can cause inflammation of your liver. But often acute hepatitis is very commonly caused by viruses. I would argue that, in fact, we are just very uncreative in naming viruses because the viral hepatitises are named hepatitis A, B, C, D, and E.
I mean to be honest, like, it's not a bad.
Wait, it's not a bad It's not bad, you know. But one thing that makes it very confusing is that all of these different hepatitis viruses have nothing to do with each Did you just say hepatiti Yeah, it's terrible. All of these m M, all of these viral hepatite.
Mmm, hepatit, I think is the word that you're looking for?
No, not hepatiti erin?
Is that not the plural.
It's not the plural.
We'll see, okay, see by the end of the episode, it will be all right.
All of these viral hepatitis viruses, they have nothing to do with each other. Erin hepatitis B is not closely related to hepatitis C, et cetera. Okay. They just all are viruses that happen to affect the liver.
What that's wild?
It is it is wild.
So these are not even the same type of viruses.
Oh heck, no erin.
Okay, So that part is where I disagree with the naming.
Then thank you. Okay, I'm glad that you're finally on my page. So we're only discussing today one of these hepatitis viruses, and that is hepatitis C. Okay. And it turns out actually that TPWKY listeners are very familiar with this family of viruses that hepatitis C belongs to. Hepatitis C is a flavavirus.
I was bowled over when I saw that.
I know, it's very cool. Yeah, So if you like, if these words like flavavirus are confusing to you, don't worry. You're not alone. Flavaviruses include dengay, the one we just talked about a few weeks ago. Also yellow fever, et cetera. Okay, if you remember, yellow fever is called yellow fever because it is a favor that turns you yellow because of its effect on your liver. Right, Okay, So, like the
other flaviviruses, hepatitis C is an RNA virus. Hepatitis C, like many RNA viruses, has a huge amount of what we call antigenic variation, so it has a lot of different antigens on its surface like the flu does, okay, influenza, So that means it's really hard to target from a vaccine perspective because it has a lot of variation. There's a whole bunch of different targets. It's hard to get them all. They're constantly changing. RNA viruses also have really
high mutation rates, so they evolve very quickly. Hepatitis C is one of those so spoilers. We don't have a vaccine, But unlike many of the other flavaviruses, you don't get hepatitis C from mosquitoes.
Which I find very interesting. Also, but there are also there are tickborn and non vector born flavvivirus.
Viruses yeah, there are absolutely, and you do get hepatitis C from blood, which ultimately is where mosquitoes get flaviviviruses from anyways, So yeah, you're just missing the vector. So hepatitis C it invades your liver cells, your hepatocytes, that's where it tends to replicate, and then it bursts out into your blood stream and circulates in your blood. So it's transmitted person to person when you come into contact
with that blood. So in the past, when blood products weren't screened properly, and I know aarin you're going to talk a lot more about that, right, Oh, yeah, yeah, blood products were a very big source of infection prior to screening. In some areas of the world. Blood products are still a source of infection if it's very difficult to screen or if there's not access to good screening tools. But hugely important are actually medical tools used in things
like surgeries, injections. That's actually one of the most common sources of infection today is medical injections using not properly sterilized needles or glass syringes. And then the other big source of infection today is injection drug use. It is possible to get infected via sexual transmission. But it's honestly very rare. It's not like hepatitis B, which is much
more likely to be transmitted sexually. So okay, okay, So Aaron, I think I told you last week, like, oh yeah, hepatitis C is going to be so easy for me to research. It's like really straightforward, we know a lot.
Yeah, you were like, oh, it'll take me no time.
Yeah.
Then you texted me today and you were like, oh god, uh, it took.
Me forever, and Aaron I, I'm not going to have answers to any of your questions. Ah, Aaron, Okay, So let's talk about how you get sick from hepatitis C.
Okay.
While it can and often does cause an acute hepatitis, which we'll talk about the symptoms of in just a second, the biggest issue and most dangerous part of hepatitis C is that, in between fifty to eighty five percent of cases, it results in a chronic infection that can eventually result in liver failure and or liver cancer and death.
First question, Oh god, okay, sorry, fifty to eighty five is quite a big range. What determines whether someone is going to become chronically infected or not.
Excellent question. There's a number of different things comorbidities. So things like having diabetes can increase your risk of chronic infection. Heavy alcohol use, especially more than fifty grams of alcohol a day, which is like four alcoholic beverages a day, can increase your risk of chronic infection. Being immuno compromised, for example, coinfection with HIV definitely increases your risk for
chronic infection. So yeah, things like that. The amount of virus that you're infected with is not actually associated with whether or not you develop a chronic infection, which is different than a lot of other viral diseases that we see.
Okay, if you get infected with hepatitis C and then you do not develop chronic infection, can you get reinfected and then develop chronic infection? Okay, so you're not like immune, which I guess is then the struggle with creating a vaccine.
Yep, Okay, good question. Okay, So chronic infection means in this case that even though a person might not have any symptoms, the virus stays in their body, continues to replicate and many many years where talking like ten twenty thirty or more years down the line can result in serious disease. So then the question that we that I always like to try and answer on this podcast is how does this virus actually cause disease? Yeah, Aaron, we don't know.
What do you mean? I mean, we don't know.
So here are the things we do know.
Okay, when hepatitis.
C invades your liver, it does stimulate an immune response. So your innate immune system which I think we talked about the innate versus adaptive immune system in the first vaccines episode if you want like a really nice intro to your immune system. But basically, the very nonspecific first immune response is triggered when you get infected with hepatitis C. However, for some reason that is unclear, the downstream effects of that don't really happen in a lot of people infected
with HEPSI. So what that means is, you know, you have your first line defenders like macrophages and stuff that come in release a bunch of chemical signals to trigger things like natural killer cells, which we talked about in the Vacciness episode, that are supposed to come in and kill any viral infected cells. So that that virus doesn't continue to replicate. Something doesn't work right in that response
when you get infected with HEPSI. So we know that people who develop chronic infections with hepatitis C, which again is the majority of people who get infected, they don't have a good T cell response, so their T cells aren't responding well to fight down this infection. But that's all we know. We don't know why. We don't know how to predict who is going to do a good
job of fighting off the infection versus who isn't. And we don't know what the virus is doing specifically to cause these changes in people's immune response that it gets worse, it gets therein.
Okay, Okay, I'm just shocked that we can treat this, dude.
This is why I thought we knew the answers to these questions, because the amount of advances that we have made in treatment for hepatitis C over the last like five years is bananas. Yeah, So I was like, of course, we know, Yeah, we got tons of treatment, we can cure it now, no big deal. So I mean, not no big deal, But you know, I thought we knew, Aaron, we don't know, and the other thing is like the whole cancer thing, which we're going to talk in more
detail about. Actually we're not because we don't know. We don't know how hepatitis C causes cancer. We don't no, it's the title of this episode, hepatitis C. I don't know. We don't know.
Wow.
Okay. There are six different genotypes of hepatitis C. Overall, they're not associated with different risks of ultimately liver failure. But genotype one B is one of the most common genotypes, and that one is associated with an increased risk of liver cancer. Okay, but it's not because we don't know why. It's not clear why, of course.
Yeah, oh my.
Gosh, who knew? I didn't. Well, let's talk about what we do know, and that is the signs and symptoms. So, in an acute infection, the incubation period, so the time from when you first get infected to when you first show symptoms, is actually quite long. It's usually like around
seven weeks, okay, which is pretty long. Only about thirty percent of people infected with HEPC will actually have acute symptomatic infection, and generally this presents with malaise, so feeling fatigued and feeling crappy, you often get nausea, which isn't surprising since your your liver is very involved with your
GI tract, you know, and right upper quadrant pain. Your liver is in the right upper quadrant of your abdomen, so your liver hurts, okay, and then what you also get is dark colored urine, And that's because you get an increase in bilirubin, which is basically a breakdown product of your red blood cells that your liver is supposed to get rid of. But your liver's not working right, So then bilirubin builds up and you have to pee it out.
Huh.
So instead of your poop being poop colored, your urine is kind of poop colored. And then as that bilirubin continues to build up, that's when you see things like jaundice. So that's literally your skin turning yellow from how much
bilirubin is circulating in your system. Right. Another huge thing that you see in acute hepatitis infections are if you test your blood to look at specific enzymes that your liver produces, they will be off the charts high, like thousands of times or at least tens of times elevated on what they normally are, and that's a really big sign that you have an acute That means first time,
shortly after you get infected hepatitis infection. Okay, But for the most part, acute infection, even when it's symptomatic, is self limited. So with hepatitis C, you are very unlikely to die from what we call fulminent, which is like very rapidly progressive acute liver failure.
Okay. The real risk comes in the chronic.
Exactly exactly, And in general disease symptoms are pretty long lasting. You can be sick anywhere from like two to twelve weeks, but for the most part, people do recover, okay. In the case of hepatitis C, however, up to eighty five percent of infections become chronic, and for the most part, during this chronic infection, a person won't necessarily have that
many signs or symptoms. If you were to test their blood, they might still have slightly elevated liver enzymes, but you can see these elevations in liver enzymes from a number of different things, so it's not like that specific to chronic hepatitis infection, okay, But progressively as this infection kind of goes along its course. The biggest symptom that people tend to experience is fatigue, like really bad fatigue, never never really feeling fully energetic. It's kind of one of
the biggest symptoms. But as we'll talk about, there are some other symptoms that you start to see, especially as the disease progresses, because basically what's happening inside your liver is fibrosis. So fibrosis is the result of chronic inflammation in the liver that leads to scarring. Very mild. Fibrosis can be reversible. But what happens with fibrosis, especially when it's a chronic infection, is that it progresses to what we call cirrhosis, which is kind of the end stage of fibrosis.
Huh okay, I realize that.
Yeah, I didn't either. I had to double google it to make sure I was saying it correctly. I should know these things, Arin, I'm going to be a doctor.
That's what Google exists for.
Yeah, I checked doctor Google too.
So oh oh good.
So cirrhosis, which is kind of the end stage fibrosis. It's like your liver is so fibrotic, it's all It's like your liver is supposed to be nice and red and beefy looking, but when it starts to get progressed from fibrosis to cirrhosis, it gets hard, it doesn't move as much, it can't. The blood flow is really bad. And this happens in about twenty to thirty percent of people with chronic hepatitis C infection.
Wow, that's a lot.
It's a lot. Yeah, And cirrhosis itself can lead to liver failure and eventual death, but in the case of hepatitis C, it's also associated with an increased risk of hippatocellular carcinoma aka liver cancer. Okay, so what are some of the symptoms that we see when you progress all the way to cirrhosis.
I don't know what are they? Let me tell you.
So the symptoms are. They can be severe depending on how bad you know, how bad the fibrosis has gotten if it's truly cirrhosis at this point. Fatigue is still a big one. Muscle weakness is another because basically, just like your liver is in charge of doing a lot of things to make products that the rest of your body uses, and if your liver can't do that, then your muscles and things can't work the way that they're supposed to.
Gotcha.
When you eat food and you absorb nutrients, all of those nutrients get absorbed into your blood stream. All of the blood from your whole GI tract, for the most part, travels to your liver through one big vein called the portal vein. Okay, so all of the blood from your GI tract for the most part, is going to your liver, and then your liver is going to process all of that.
Okay.
As your liver starts to become serotic and hardens, that closes off that blood vessel and so it basically puts increased pressure on that portal vein and it backflows it. If that makes sense.
Ooh, that sounds terrible.
It is terrible. It's like squeezing the end of a garden hose, right, yeah, And that garden hose that goes to your liver when it backflows, it backflows into your GI tract, and so this can cause all of the veins associated with that to then start to dilate. So this can cause what we call verices or varicose veins. You've heard of those in like your legs. Yeah, well you can get those associated with your gi tract, so around your belly button you can get huge amounts of
varicose veins. You can get them in your esophagus because even your blood flow from your esophagus goes to that portal vein, and those, if they're under too much pressure, can burst. Oh my god, and then you can bleed out and die because what's mm hmmm, m yep, that can happen. Another thing that can happen if you think of closing off the end of a garden hose, how much pressure you can build up in that garden hose.
Eventually that hose is going to start to leak from the sides, right uh huh, It's going to like spew liquid out water out from the sides. The same thing can happen in what we call your portal tract in that portal vein, which can cause the fluid that's supposed to be in that vein to start leaking into your abdomen. So you can get a huge amount of fluid in your abdomen. That's what we call ascides.
Oh my gosh.
I have seen people in liver failure not necessarily from hepatitis C, but from cirrhosis that we've drained eight liters of fluid from their belly.
Where is that liquid coming from from?
It's from your bloodstream, like you retain it, I know, but eight leaders, eight leaders. It's it's not good. That's like really bad. So yeah, you can imagine that that can cause a lot of complications, right, A whole bunch of fluid just in your abdomen that can be anidis for infection, so you can get abdominal infections because of it. It also is just putting a lot of pressure on
all of your organs. All this pressure in the veins can lead them to burst, like I said already, So in general, liver failure is not good news.
Well yeah, and then some of.
The other signs and symptoms that we see are similar to what we see in acute liver disease, So things like jaundice, weakness. Itching is a really big one because as bilirubin builds up and actually causes a really intense itching why I don't really know, I'm not really sure, but it does just makes you itchy.
Interesting.
And then hepatitis C can actually also have extra hepatic so outside of the liver manifestations, especially by increasing abnormal proteins in your blood, which can have issues like making your blood too thick. Blah blah blah. Hepatitis C is not a good disease.
Well, it's horrible.
It's horrible. And the big sea in hepze cancer I mentioned already it's generally only associated with cirrhosis, So cirrhosis becoming cancer in people with hepatitis C. That's not true for liver cancer. That's not associated with hepatitis C. Like you don't have to have cirrhosis to get liver cancer, but in people with hepatitis C, they generally have cirrhosis first and then liver cancer.
And so are there differences in the types of liver cancer that you get, Like is the hepatitis C associated liver cancer different than alcohol associated liver cancer or just good question.
There are different types of liver cancers. What's associated with hepatitis C is called hippatocellular carcinoma. That's the same type of liver cancer that you would get in associated with very heavy drinking or with hepatitis B, which is another major cause of HCC. Hippatocellular carcinoma. But in general, HCC is actually a pretty rare complication of hepatitis C infection. It's about one point five percent one to three percent I've seen overall of people with chronic infection will go
on to develop HCC. How exactly this chronic infection results in cancer, I really thought we knew erin I mean, cancer is associated with high levels of inflammation, and we know that this causes chronic inflammation. So maybe it's as simple as that. But the true mechanism, the way that we know it for like HPV, we don't. I don't know in this case. Okay, So yeah, the good news is that there is treatment.
That's great news.
It is great news, and it's fascinating and amazing to me because we've made massive advances in treatment in the last few years. So it wasn't until I believe twenty thirteen that the first what we call daa direct acting antiviral, so that's an antiviral that directly attacks and blocks the replication of hepatitis C virus was put on the market
in the US, at least was in twenty thirteen. Prior to this, there was still treatment, but it was a combination of something called interferon, which is actually one of those mediators of immune response that our body uses naturally,
and another antiviral called ribevierin. This was used before we had these DAAs and it did result in like forty to sixty percent of cases being cured, but treatment took forever, like almost a year, if not more, and there was a ton of side effects and it was really difficult
to tolerate. So the introduction of all these new I think there's at least eight now direct acting antivirals DAAs has been massive because now treatment usually only takes eight to twelve weeks, It could be up to twenty four depending on how severe diseases to begin with. But cur rates are above ninety percent.
That's really cool. If you're going to afford the medication.
Yep, that's the asterisk. The cost of these medications, it varies hugely. It's dependent both on whether there's a generic formulation, and since a lot of these drugs are super new, there might not be generics yet, and also what country you're looking at, So these can vary anywhere from fifteen dollars to twenty five hundred dollars for a one month supply of some of these drugs.
Can I guess which country is the twenty five hundred dollars.
And actually none of these were in the US.
Actually what Yeah, okay, so the US is twenty five thousand dollars a month.
Maybe I didn't see numbers for the US, but yeah, but yeah, but it is. That's one of the biggest challenges now that we have a way to cure it is both identifying disease because there are so many people living with hepatitis C that don't know that they're infected, and actually getting this drug or these drugs to people who are infected. So there's a lot of people who are infected and know they're infected but haven't yet had access to these curative treatments.
Right.
So yeah, that's the biology of hepatitis C.
Huh, so much?
We don't know so much? Do we know anything? Oh? I don't know, So tell me erin. What's up with this? How did it get here? Why are we so bad at screening blood?
Or are we great questions Let's take a quick break. As you mentioned, the hepatitis C virus is a pretty recent discovery and so the history of it is pretty short, like pretty short. The virus itself was only discovered or named in nineteen eighty nine, but researchers knew of a non A, non B hepatitis virus for a little over a decade before that. Around nineteen seventy five was when
it was kind of first recognized to exist. But before we get in to too much of the medical history side of things, I want to talk about the evolutionary history of hepatitis C.
Please.
For a long time, researchers assumed that hepatitis C virus had its roots in a non human primate hepassavirus. Okay, but then they discovered hepatitis like a hepatitis CE like virus in horses and dogs, which suggests that these viruses might be more widespread throughout mammals than previously thought. Okay,
so where did they come from? Okay? Looking at the genetic diversity of hepatitis C virus, there seems to be the most diversity in sub Saharan Africa and in Southeast Asia, and so that's probably where it had been circulating for a really long time in humans for who knows how long. But by the way, how it circulated in these populations
is not clear. Because, as you mentioned, it's bloodborne. So there are a bunch of hypotheses ranging from mosquitoes it actually being vector borne fascinating, to sexual transmission, having it play more of a role or like circumcision practices or other things like that.
Interesting.
Yeah, so it's kind of unclear. It's the theme of this episode. But how long did it circulate? And that is also a really hard question to answer. Shockingly, listeners,
We're sorry. There are models based on the genetic diversity of the virus that put the origin of hepatitis no more than a thousand years ago, Okay, which doesn't really seem possible given the hugely widespread nature of the virus, which we know is a more recent thing, but the fact that it exists in different genotypes in isolated populations, like geographically isolated populations. Yeah, and so maybe we're missing something about the replication of the virus itself, about how
mutations accumulate this sort of thing. I mean, the short answer is we don't know. So that's the idyl. Let's get into the stuff that we do know, and that is how it became global over the past one hundred years. And by global, I mean like really global I know this is maybe preempting you a little bit, but how many people are estimated to be infected with hepatitis C worldwide?
Do you mean estimates from today or like four years ago, because I've seen very different estimates.
I've seen very different estimates too, and I can't tell whether it's like super optimistic.
At least seventy one million, let's say.
That, right, and then the higher estimates are around one hundred.
Seventy seventy million, Yeah.
Exactly, so up to two and a half percent of the world population.
Yep EPI section over. What the heck?
What the heck? I mean, that's an enormous number of people.
Yeah, it really is.
And the reason that I wanted to mention those numbers now is because a big part of the story of hepatitis C is not just in the history of its discovery and medical advancements and treatments and so on. I mean, those are really important, but I think it's really important also that we understand how we got here. How on Earth did seventy two, one hundred and seventy million people become infected with this virus?
Yeah?
How, I mean, it's a complicated question to answer, but because there are many different parts of it. But a big part of that answer is, as you mentioned, through blood transfusions and other blood products. And so even though the history of hepatitis C is a short one, the history of blood and blood technology is not, and those histories are intertwined. So I decided for this episode to focus on the blood transfusion side of the story.
Awesome and holy count.
It is so much more interesting than I thought it was gonna be. I had a really fun time researching this. Okay, blood is a precious resource. The cost of a barrel of crude oil as of January twenty twenty is about fifty eight dollars. Okay, the cost of a barrel of blood would be about sixty three thousand dollars, and I estimated that based on the cost of like a gallon of blood.
I'm sorry, yeah what yeah, wow, uh huh.
But even more than the monetary value of blood is of course, it's life saving qualities from blood whole blood. You can get white blood cells, plasma clotting factors, antibodies, and then there's of course blood itself for transfusions. It is vital. It is a life giving liquid and as you might expect. This quality of blood has led to
it being revered for millennia. It's impossible to give a history of blood itself and how it's been viewed throughout history because the scope would be enormous, Like which cultural lens are you going to look through? Which myths are you going to write about? So let's pick this story up from where this life given quality of blood first started to be tested. Blood had long been recognized as one of the four humors of the body. This was
like the presiding medical theory. So it was along with phlem, collar and bile. I like that Flem makes the cut, I know, bring back Flem. Then this whole like humor theory of the body dates all the way back to ancient Greece, because I have to mention that in an episode. Oh contractually, But how blood traveled throughout the body its circulation wasn't discovered until sixteen twenty eight.
Whoa yeah.
The first attempts at transfusions followed shortly after, mostly using animals, and they were unsuccessful, as you might.
Expect, like animals into humans.
Animals into animals.
Oh okay, okay, yeah, okay.
We'll get there. We'll get there. So in sixteen sixty six, the first known successful blood transfusion was performed. WHOA an English doctor named Richard Lower took two dogs and from one he drained as much blood as possible without killing it.
I do remember this, actually, I knew this story.
I'm going to keep telling it anyway, do it please. With the other dog, he sewed a reed to one of its neck arteries and attached the other end to the jugular of the barely alive dog, and he allowed the blood to flow from one dog to the other until the one that was giving the blood died and the other one that was receiving the blood revived, stitched him back up, and then the dog essentially came back to life. He like within a few minutes. He was
back on his feet. It was running around and seemed perfectly happy, even with his dead comrade next to him.
I's going to say the other one was dead. Cool.
Yeah, But this, even though it was a very gruesome experiment, it cracked open the world of possibilities to both physicians and philosophers. How could this be used to save lives by transferring blood from one animal or one person to another. Would the recipient take on the qualities of the donor. Can you make a tame dog vicious by the transfer of blood? Could you change your personality by getting someone
else's blood? And so while the philosophers were busy debating the ramifications of blood transfusion, the scientists were busy refining the technique. Soon it was possible to conduct small transfusions enough to keep both the donor and the recipient dogs alive. But it wasn't all good news, not just because probably many many dogs died along the way, because people almost immediately started experimenting on humans transfer blood from a cow to a human for example.
Oh, no, bad idea.
Yeah, uh, he survived.
Wow.
It was also done on like he was. He was forcefully volunteered, of course, you know.
Nobody volunteers for those quote experiments.
No, they did this to him because they were like, oh, he's a he's a drunk, he's mean to his wife. Let's see if we can make him more docile with the blood of this gentle cow. And so he did seem to be, you know, a little bit calmer after that, probably because he was like exhausted and had been close to death. Yeah, And then a couple like a year later or a few months later, he shows back up. His wife is dragging him there and uh and she's like, you got to do it again. He's he's back to
his you know, normal state. And so they did it and then he dies.
Yeah.
Turns out in the tree she had been poisoning him all along, and so he actually died of arsenic poisoning. No way, isn't that great? I love that?
Oh my god, that's really funny.
Okay. But even though you know, not all of these transfusions were successful by any means, people started to see the possibilities in this. People were still dying by the bucket load from infectious diseases like smallpox, plague, cholera, you know the ones. What if these physicians wondered, people could be cured of such illnesses by transfusing healthy blood, like from lambs into sick people, specifically lambs specifically. Yeah, so
they tried it, didn't Karen. I mean, you know, to read some of to read the reports of some of these experiments, you'd think that they discovered a miraculous cure.
Ale.
Wow. They started making claims that not only could fresh lamb's blood be used to cure leprosy and scurvy and so on, but also unfavorable personalities or the other thing that they tried, and this was human to human, was to resolve marital conflicts by swapping the blood of wives and husbands. Just blood with my heads.
Wow, Well, I should ask him if he'd be into that.
You should try it, transfusing spouses.
I love it. Wow.
And by no means were these new transfusions widely accepted. Some people believe them to be the work of Satan, or at the very least, completely useless in curing any of the diseases that they were supposed to do. Okay in this bad press, in addition to a couple of deaths following transfusions and a wrongful death trial, led to
the premature end of blood transfusions. In less than five or six years after the first successful transfusion, blood transfusions in humans were banned in France and England, and the Pope banned the practice in the rest of Europe.
Wow. Yeah, five years.
It was like a real one to eighty slash in the pan m hm. And it would be more than one hundred and fifty years before doctors experimented again with blood transfusions in humans. Huh huh. So in eighteen eighteen, an obstetrician in London decided that he had to try something to reduce the enormously high mortality rate of people bleeding out after giving birth.
Ah.
So he tried a few transfusions, with varying degrees of success. It's like fifty percent, okay, But even with this low success rate, what this did was get scientists interested in transfusions again, and they gave themselves license to experiment as they wished, and experiment they did. While there were some milk transfusions, for instance, most doctors restricted their material to
human bloody. Sorry, time out, how what yeah, something about the uh, the proteins and fattiness and milk would but.
Where do they put the milk in the blood?
No? No, it didn't. That one didn't last long. It wasn't super popular. I don't know if that experiment was repeated.
Okay, okay.
Most people fortunately just used human bloody. But even then, there were many ways a blood recipient could die. Physicians didn't know anything about blood groups, clotting factors, sterile technique, et cetera, et cetera. So about fifty six of one hundred blood transfusions during the eighteen hundreds ended in death.
That is more than not.
It is more than not. And it's probably likely that at least some of these people were going to die anyway. Okay, But you know, despite these not so great numbers, people didn't abandon the procedure altogether. And that's probably fortunate because the discovery of blood groups was just around the corner.
The guy who discovered blood groups like a b abo, etc. Okay, whose name was Carl Landsteiner, made some seriously impressive predictions about how different blood types could behave when introduced to one another, and suggested that this knowledge would be really useful in increasing the success of transfusions, and that would win him the Nobel Prize. But even still, nobody really paid much attention for a while to this. Yeah, kind
of strange. Eventually they did so throughout the early nineteen hundreds, they refined the technique a little bit, but doctors would just sit by their patient side and kind of guess by intuition alone when their patient had received enough blood.
You're looking, pinker, he'll do Yeah, seriously, that was basically it. Okay, they didn't always guess correctly, and then there was a huge issue of blood doing what it does, which is clotting, so it would come up the works like very rapidly until sodium citrate was discovered as a non toxic anticoagulant. And then the world of transfusions was open to basically everyone, like it was, as long as there was a willing donor, you could get the job done. Doctors weren't yet storing
blood for later transfusions. They typically needed someone then and there like a donor on the hoof, I think is what they called it.
So you would just like go into the surgery or go into the whatever, Yeah, and be the donor at that time.
Yep, exactly, And this could be a lot to ask of someone, and so arose the practice of selling or buying blood and the field of professional donors. And remember this is the early nineteen hundreds when microbiology as a field was just a few decades old and the causative
agents of many diseases were unknown. And the decades that followed saw the creation of the earliest blood banks and improvement in storage techniques, but arguably the biggest progress came, as you might expect, during World War II, it's no coincidence that this is also when hepatitis C began its global spread.
World War two.
World War two, so millions upon millions of people were dying or getting seriously injured, both military and civilian, and also traveling all around the world and then returning home hopefully at the end of the war. So with all of these injuries, there was not only a huge need for blood, but also a need for improvement in blood technology. And we've talked before about how much antibiotics revolutionized medicine
during the war. People weren't as likely to die from infection from minor wound major wound after the discovery of penicillin. But before during this episode, I didn't realize just how much of an impact freeze dried plasma made on survival as well.
Yeah, that makes sense. I didn't I wouldn't have thought of that either.
But like, yeah, oh it was remarkable. Yeah it Like so, freeze dried plasma was just add water, I guess, was a field ready way to reduce shock and restore blood volume, and this alone probably saved thousands of lives.
Wow.
Blood whole blood was less of a focus because it was much more difficult logistically to store and handle and so on. Yeah, and so military doctors looked on the plasma as a miracle. Soldiers would be going into shock with severe wounds and then they would bounce back from death with the injection of some plasma.
Wow.
But these doctors also recognized plasma's limitations, so the positive effects were often short lived, and the wounded appeared to be starved for oxen, unable to get warm, and then would sometimes slip back into shock.
Since there was no red blood cells exactly to carry oxygen.
And so although plasma was pretty awesome, it was no replacement for whole blood, and the problem was where to get it. During the war, there was a shift from paid donors to volunteer donors because there just wasn't enough blood coming in and so they were like, oh, you know, support the troops campaign, like for community, that sort of thing. But at least in the US, this blood wasn't being shipped overseas because the logistics of keeping blood cold during
transport was difficult. As a result, there was a constant shortage of blood and some doctors had to resort to being impromptu donors oh gosh, yeah, or employing the whole donors on the hoof methods had been used previously. After the war ended and the pressing need for blood decreased, the blood banks and blood donor organizations didn't fade. They
actually grew enormously. The threat of nuclear war between the US and the USSR kept people running to blood banks to donate, because if a nuclear attack happened, the immediate need for blood would be greater than maybe like the entire war combined. People recognize the problems with paid donors, though, and the American Red Cross, along with smaller blood banks across the country, focused on convincing the public to donate blood out of a sense of community. But there was
a darker side to this. Racism and blood donation had existed since the modern history of blood transfusions, and it
didn't stop after the war. Even though scientists repeated over and over again that blood was blood and you couldn't tell a person's race based on their blood, the Red Cross and other blood donation centers still practice the racist regulations of only allowing white people to donate, or when that rule was overturned, they forced people to label the blood so that a recipient could then see or choose whether they wanted to receive that blood.
Are you I shouldn't be surprised by this erin.
It was probably less of the patient and more of the hospital. Yeah, of course, yeah, there could have been the patient too, but just.
The fact that it like that was the Red Cross practice.
Eventually, these racist practices died out, not soon enough, and then they would later be replaced by still screening blood based not on the blood but on the person who's giving the blood yep, which is really problematic to say the least. Yeah, But ethical and legal issues surrounding blood donation continued to pop up or re emerge, mostly focusing
on whether blood could be considered a commodity. So around the real different countries had debated whether or not to pay donors for their blood or to rely on volunteers, and the US was one of these countries that was sort of copy between those two things, and the ethical issues with paying for blood were obvious to everyone. There was exploitation of more people who were literally selling pieces of themselves as a way to make money, which is an issue that continues to be a problem in paid
medical studies. But we're not going to get into that.
It's a different episode.
It's a different episode.
Ye.
And then the fact that there was still no good testing for certain infections such as hepatitis, even though HEPSI was not yet known. And then came the legal and moral ramifications of whether blood was considered a commodity, because if it was, it was then subject to federal trade and commerce laws in the US, and if it were considered a product, it was subject to the Uniform Product Code, which was a regulation that stated that anything sold as a product of commerce carried an implied warranty.
Huh.
But blood banks, both nonprofit and commercial, couldn't easily guarantee the safety or quality of the blood they were peddling, so they sought and gained an exemption to this by getting blood to be labeled a service, which is why it was so difficult for anyone to sue blood banks after being infected with contaminated blood.
Fascinating wow.
And in the US, prisons were a huge source of plasma for a very long time and outrageously unsanitary conditions and at least one group of prisons in Oklahoma owned
by a physician, Yeah, he owned six prisons. What it was a site of enormous hepatitis infections in the nineteen sixties, and so I should point out that at this time, so throughout the sixties and fifties, basically and even before then, hepatitis, like as you mentioned, hepatitis as a condition inflammation of the liver was recognized, and it was even known to be associated with blood transfusions. Okay, but no one, of course knew what the causative agent was for a long time.
And I'll get there. And so usually the hepatitis was diagnosed based on clinical symptoms, so like the jaundice and the inflammation and all of that, not on finding a virus. Yeah, even though hepatitis was a known problem in blood transfusions, people in the blood business looked at it as well, It's better to live with hepatitis than die of not
getting blood, so it's an unfortunate but necessary risk. During the fifties and sixties as well, injection drug use also started to really pick up and become widespread, and so the combination of a massive increase in blood donation and blood transfusions and injection drug use really also helped to
spread hepatitis and other blood borne pathogens. And hemophiliacs were one population that experienced dreamly high rates of hepatitis C and of course HIV, as we discussed in that episode, due to their need for multiple transfusions or factor eight, which was made from plasma. In the early nineteen seventies, the CDC put transfusion related hepatitis deaths at thirty five hundred per year.
Whoa wait in what year again?
Nineteen seventies, early nineteen seventies.
Wow, just transfusion related hepatitis.
Deaths well, and many physicians actually argued that that number was ten times.
That Holy guacamole.
And this wasn't just a problem in the US, this was a global problem. I'm focusing on the US because that's where a lot of the book took place. But anyway, Europe, who relied solely on unpaid volunteers, condemned the US practice of using paid donors, but they constantly bought plasma the US,
they had a constant plasma shortage. And so yeah, and when a test for hepatitis B was finally developed in nineteen seventy five, which was only forty percent effective, actually better than the fifteen percent effective tests from nineteen seventy two, people could finally start screening blood, and what they found was that paid donors were three times more likely to be infected with hepatitis compared to unpaid donors.
This is hepatitis hepatitis B.
Yes, And then there were arguments over whether to completely eliminate paid donors, until the FDA said in nineteen seventy eight, hey, let's let the market decide, and they forced blood banks to label blood as being either from paid or unpaid donors. Almost immediately, the practice of paying donors for blood was over. Wow, but they did not. Nobody, no hospital bought paid donor blood.
Huh.
Plasma was another story.
Yeah, you can still get paid for that. Yeah.
I remember in college I had friends who would go donate plasma for money, beer money, and then they would be like, oh, it's great, like you get so much drunker faster because whatever.
That's a terrible practice. Nobody do that.
Nobody do that. So a few years after this ruling by the FDA, rates of hepatitis B dropped, but people were still getting hepatitis from transfusions. An investigation revealed that ninety percent ninety percent of transfusion related hepatitis was not caused by hepatitis B. But by something they couldn't test for. Ooh, they called it non A non B hepatitis.
Yeah, non A non B. I'm guessing it's C.
Yep.
Easy.
In nineteen eighty four, five years before the new virus would get a name and a test, it infected an estimated one hundred and eighty thousand and blood transfusion recipients, killing about one percent of them.
Is that in the US alone? Uh?
I think that's global?
Okay because that seems whoa high?
Yeah, I think that's global because that's just in one year.
In one year, that's a massively huge number of people.
So in nineteen eighty nine and beyond, once researchers could identify hepatitis C cases, they started to get a better sense of how the virus behaved, and what they saw was super concerning because of all of the things that you said, And whereas hepatitis had previously been seen as this unfortunate risk of blood transfusions, this new information about hepatitis C was like, okay, no, there's an increased urgency for a clean, uninfected blood supply. And that coincided also
with the AIDS pandemic beginning. Those two things combined, particularly urged on by the AIDS, pandemic, really led to a complete reform of blood screening and blood transfusions. But even though blood donation regulations really changed to decrease risk of any sort of blood born infections, damage had been done in a lot of ways. Over time, the positive effects of these new regulations, in addition to the introduction of things like needle exchange programs, really did start to slow
this hepatitis ce pandemic down within thirty years. Like the virus was discovered in nineteen eighty nine.
Thirty years ago.
Thirty years ago, it was discovered, a test was developed for it, and an effective treatment was created.
That's so I'm just so interested in that, Like, is there a story like that for any of the diseases that we've talked about thirty years to go like that rapidly. I know that it's because we discovered it so recently, you know, Like, whereas diseases that were discovered so long ago. Of course it took them longer to figure things out. But I just think that's so so fascinating.
I mean, hiv IS is along those lines.
That's true.
It's not true, it's not the death sentence.
It once was absolutely.
But you know, in terms of hepatitis C, we're still far away from elimination or eradication. Yeah, there are still, as we mentioned, millions and millions of people infected with the virus around the world, and new infections continue to occur. Aaron, tell me about hepatitis today and what's being done.
Would love to. We'll take one more quick break before we jump in. This section is actually going to be very short. We kind of already talked about these numbers, so let's just repeat them for everyone. It's unclear to me exactly. I'm sure it's unclear to the globe exactly how many people are currently living with hepatitis C. But we know it's at least seventy one million, which is what the WHO the World Health Organization estimate is based
on twenty fifteen numbers. Okay, However, if you look at numbers from just a couple of years previously, it could be as high as one hundred and seventy one hundred and eighty million people.
Yeah, what caused the drop of one hundred million people?
I think it's just depending on what model people were using and what years of data they were using. So if they were using data from like the eighties and nineties and then modeling out from their infections were higher than if they used numbers from the early two thousands. And it's because of those blood transfusion screenings and things like that. So at least that's from what I understand, that's what it seems like. But here's where I mean
either way. Seventy one million people, that's seventy one million people living with hepatitis C. The WHO also estimates that there's over one point seventy five million new infections every year.
Oh my gosh.
And they estimate that four hundred thousand people die every year as a result of hepatitis C. How many four hundred thousand people? Wow? And this is now a curable disease. So nobody in theory should be dying from hepatitis C. Right, And the biggest issue is twofold one. It's estimated that only nineteen percent of all people who are living with hepatitis C actually know their diagnosis.
Wow, that's very low.
It's very low. And of those diagnosed, only about five million people. So it's estimated that thirteen of those seventy one million people, thirteen million know their diagnosis. Only five million of them have been treated as of twenty seventeen, so there's a huge amount of work that needs to be done to get those people the treatment that they need.
Yeah, what is what's being done well?
The World Health Organization has a huge hepatitis initiative and they have a number of different ways that they're trying to increase access to these drugs and also increase access to screening because one of the issues is while initial screening tests for hepatitis C, which are antibody based, so we can basically just take your blood and see if you have any antibodies to hepatitis C. Those tests are pretty easy and pretty like less than two dollars, but
they're not specific. So while they'll tell you yes, you were exposed to hepatitis C, remember that eighty five percent or less of people actually go on to develop chronic infection, so it might just mean that you were exposed to hepatitis C, but you've cleared the infection. The tests to actually know whether you are currently infected chronically with hepatitis C are more expensive and often require expensive equipment and
specialized technicians to be able to do those tests. Because they're often PCR based tests or antigen based tests, so looking for the actual virus itself in your bloodstream. Right. So that's one of the things is developing better diagnostic tools that are cheaper, easier to use, things like point of care testing, which means you can when you have somebody there and you want to test them, you can
actually do it right then and there. That's huge, not just for hepatitis C, but for a number of different infections people are working on. And then the other thing is treatment. So while we have treatment, it's very expensive in a lot of cases, and so getting people access to these drugs is difficult, even though it's hugely important, and so that honestly, it takes money, and it takes pharmaceutical companies being willing to sell their drugs for cheaper Ah.
Okay, so let's find something else because that's never.
Going to happen. Yeah. The other thing is a vaccine. I actually don't know how much progress has been made on a vaccine thus far. It's very difficult because of how much variability there is a hepatitis SEE and how quickly it mutates. It's really difficult to develop a vaccine. The other issue is since we don't know a lot about how it interacts with our body, we don't know how good of an immune response we'd be able to
generate with a vaccine, if that makes sense. So it's unclear if how good if we can develop a good vaccine at this point. But I'm sure there are people working on it. Because this is a human specific disease. I'm not sure that I even mentioned that, but with any human only disease, it is theoretically possible that we could eliminate it, but at this point that's not even
an option. And so one thing I would like to say is that while in the US and much of Europe, Australia, other places, blood products are very very very safe at this point they're very well screened, that's not true everywhere. So in some places it is still difficult to test blood products for every possible infection, but overall they are much better tested than they were in the eighties and nineties.
And because blood transfusions are generally rare, blood transfusions itself are not a huge risk on a population level for hepatitis C and today, okay, the two largest sources and risks for infection, The biggest one is unsafe medical procedures, so using glass syringes, not properly sterilizing them, using reusing needles for medical injections.
Right, which used to be common practice.
Yes, yeah, and is still common practice in a lot of places where they don't have access to disposable syringes and disposable needles. It's expensive, it's super expensive, and so that's a huge source of infection. And the other is injection drug use. So, like you mentioned, harm reduction practices like needle exchanges, distribution of sterile needles, this can be hugely effective in helping to reduce the spread of disease,
including but not limited to hepatitis C. M HM. So that brings me to what I really want to talk about in terms of hepatitis C, and that is that this is like HIV, a disease that is highly stigmatized, right because of its associations with injection drug use, and it's I think a lot of people still associate it with sex, even though that's not a huge source of infection. But in our Puritan culture, sex is bad, so you know, sexually transmitted infections are very what's the word I'm looking for,
stigmatized stigmatized. Yeah, and so one thing that I think is really great that has become a recent recommendation in the US by the CDC is universal screening for everyone born between nineteen forty five and nineteen sixty five.
Huh.
Yeah, it is now the recommendation that if you were born in those years between nineteen forty five and nineteen sixty five, and you haven't yet been screened for hepatitis C, you should absolutely go get screened. No matter what you think your quote unquote risk might be. Even if you never used injection drugs, even if you never had blood products, it doesn't matter. You should get screened. And that's because hepatitis C was so common that any type of medical
procedure could have potentially put people at risk. But what I think is great about things like universal screening is that it helps to reduce that stigma. Everybody should be screened because anybody could have been exposed to hepatitis C.
Yeah.
But the thing about screening, I think screening is really awesome, and we haven't sort of talked about what diseases make sense to screen for, like when would you screen versus when would you not screen? So I wanted to talk really quickly about what makes a disease a good candidate for screening and why hepatitis C is only recently been
a good candidate for screening on a large scale. First of all, to be a disease that it makes sense to screen for, you have to have an effective screening tool, right.
Which makes sense so pretty basic.
For there to be an effective screening tool, that means it has to be inexpensive so that it's cost effective to do this test on everyone who comes into your office, basically, and it has to have a good enough sensitivity and specificity that it's actually useful, so we know that we're getting the majority of cases of this disease and we
don't have a lot of false positives or false negatives. Secondly, you have to have a disease that's at a large enough prevalence in the population for you to actually pick it up. Since no screening tool that we use is perfect, there's always going to be some false positives and some false negatives. If a disease is really really rare, then your false positives and false negatives are going to be out of whack and there's not really a point to screening in that case. Does that make sense?
Okay?
And third of all, and this one is where hepatitis C is only now make sense. To screen, you have to be able to do something about it, because there's no real point in screening whole groups or populations if there's nothing you can do except tell them, hey, you have a horrible disease. End of story. So, now that we have such effective treatment tools, and of course screening tools are always getting better, screening is a really good recommendation for something like hepatitis C.
That's cool. Yeah, isn't that?
I really love that. Yeah, my little EPI nerd in me. So, yeah, that's basically hepatitis C. The biggest sort of obstacles that we have going forward are access to treatment and better screening tools and getting everyone who has hepatitis C to actually know their diagnosis so that they can get access to potentially life saving treatment.
I mean, it's amazing the enormous strides that medicine has made, I know, science has made in the past thirty years.
Yep, good job, good job, but also like, bad job on a lot of other things. Oh yeah, oh so sources, sources, So I got most of the information about the history of blood transfusions from a book called Blood and Epic History of Medicine and Commerce by Douglas Starr, and I recommend this book.
It has more of the discussion about the racism surrounding blood transfusions, which I didn't talk much about, but there's a really dark history to that, and screening blood by the identity of the person rather than what's in the blood has also remained a huge issue. Yeah, but read more of that book to find out more. Another book that I relied on also was Hepatitis C Virus From Molecular Virology to Anti Viral Therapy Cool.
If you'd like to know more about what's being done for hepatitis C worldwide, you can out the Global Hepatitis Report by the World Health Organization that was in twenty seventeen, I think is the most recent one. And then there's a number of different articles that I have on just the clinical disease and epidemiology. We'll post all of our sources on our website, this podcast will Kill You dot Com under the episode's tab.
Thank you to Bloodmobile for providing the music for this episode and all of our episodes.
And thank you to all of you for listening as always.
Yes, we appreciate you, we love you. Thank you for letting us do what we love to do.
It's unbelievably fun to talk about horrific diseases with my best friend. I have so many people listen.
It's the dream. Really well, with that, wash your hands, you fill the animals and hepatitis. See you later. Bum bu.
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