All the thoughts that you can find in this video will be expressed in this video. If you recall how to start, or if you're ready to start, please let me know. Well, I hope you enjoyed this video. Alright, in this video we're going to cover the serology of hepatitis A, B, C, D, and E. It's a very important type of concept that we should be really understanding because it's very utilized on like different types of boards and didactic exams. Let's go ahead and get started on that. Alright, so when we go ahead and focus on this stuff here, we need to, before we start really getting into the hepatitis B virus serology, I want to give you guys a couple different terms because it's really going to kind of pave the way for us. So remember, I told you what the hepatitis B virus it has different types of antigens, right? So if you guys remember, we're going to have on the surface of the virus, on that envelope, it has a specific type of antigen. And we call that antigen the surface antigen. And it's right on that envelope. So on the outside, if you take the virus, you're going to have the envelope and there's going to be an antigen on that outer surface there. That's called the hepatitis B virus surface antigen. The only thing I want you to know about the hepatitis B virus surface antigen is that if it is positive, okay, if it is positive, that means that the patient is infected. So if it is positive, it means that there is an infection. It could be acute infection. It could be a chronic infection. All we know is that if that is positive, the patient is infected with hepatitis B, okay? The next thing is there's another antigen. So if you take the envelope and then you come inside, there's another antigen which is going to be in between the envelope and the capsid and that is called the hepatitis B virus envelope antigen. We'll put E for envelope. Okay, if this is positive, it's indicative of two things. One is it's indicative of the virus replicating. So if it's positive, that means that there's an increase in replication. And if there's an increase in replication, there's an increased chance of infecting other cells. So it means increase in infectivity. But main thing I want you to remember here is the replication aspect, okay? And I'll explain why when we get to the chronic portion over there. The next antigen that we want you to know here is going to be, we have surface antigen, which is in the envelope. Then we go inside of the virus, underneath the envelope, there's the envelope antigen. Then we get to the capsid. The capsid has different proteins and that have antigens on it. And that's going to be called our hepatitis B virus core antigen. So you can remember core for capsid, right? And that's the core antigen. Okay. And again, this right here we don't actually measure. So we don't actually measure this, we measure an antibody against it. But I just want you to know that it's not measured. But we are going to have antibodies that are against this that we do measure. So that leads us into the next thing. The next thing is we have what's called the anti... HBS. So it's very simple. Hepatitis B virus surface antigen, the antibodies against the hepatitis B virus surface antigen. Okay. If this is positive, what does that mean? It means that the patient is cured. Or if it's positive, it could mean that the patient was vaccinated. So they were vaccinated. So it means two things. If it's positive, it means that the patient was cured. In other words, they actually were able to produce the antibodies and completely get rid of the virus, or they were vaccinated against it. The next one that I want you to know here is going to be the anti-HBC, which is going to be the core antibodies. So these are the antibodies that are against the core antigen. If these are positive, they can be in two types. You can have IgM, which that just means that it's acute, or it can be IgG, and that just means that it's a chronic infection. Okay, so you guys should know that from immunology. Positive IgM means that it's an acute infection. Positive IgG means that it is a chronic infection. Last thing that we need to know here is going to be the envelope. antibody. So we have what's called the anti-HBE, which is the envelope. So it's the antibody against the envelope antigen. And if this is positive, that means that there's a decrease in replication. and a decrease in infectivity. So it's basically opposing the envelope antigen. So it's a pretty simple concept when you think about it, right? One last thing I want to mention here is just the DNA. So there's HBV DNA. If that is positive, and we'll consider it to be an antigen as well, if it is positive, again it just means that there is increased replication. and increase infectivity. Okay. Alright, so what we're going to do now is now that we've got this all kind of set up here for us, we're going to take these little charts, which are going to have antigen on one side, and we're going to be talking about these, antibody on the other side, talking about these, and we want to look at them in different phases. Acute infection, what's called the window period, if they've recovered, if they're immunized, or if they have a chronic infection. And so we're going to be doing this for the hepatitis B virus for all of these boxes here, okay? So first things first, patient's been infected acutely. What happens to the surface antigen? Is it positive or negative? Well, they've been infected. So the hepatitis B surface antigen should be positive. That's a simple concept. An acute infection can be acute or chronic. Hepatitis B virus envelope antigen. Well, if it's infecting the cell and it's acute, it's going to be replicating, right? So the hepatitis B virus. Envelope antigen should also be positive. A simple thing. Again, we don't look at the core antigen, but we do look at the HBV DNA. So again, HBV DNA is going to be positive. Okay, going to the next part, antibodies. Anti-HBS. Guess how long it takes for this guy to really produce an antibody? It takes about six months. Okay? So you have to be cured, resolve the infection, or be vaccinated in order to have this antibody. If you've been acutely infected, do you think you're going to have this antibody present? No. Because it takes about six months. Okay? So with an acute infection, that is going to be negative. The anti-HBS. So the anti- HBs is going to be negative. Okay? You don't have the antibodies against it. What about the core antibodies? You are going to produce this one. Well, it's an acute infection, so which one should it be? IgM or IgG? It should be IgM because that's an acute antibody. So we're going to have anti-HBCs, and these are going to be positive, but of what flavor? They're the IgM flavor. Okay? Next thing is the anti-HPE antibodies. This one I don't want you to worry about right now. And the reason why is this is going to be more particularly, these aren't produced until the more chronic areas. So after the patient's either completely resolved the infection or if they have a chronic infection. But this is again more particularly for either resolving or chronic. But for right now, we're just going to say that these aren't even present yet. So these are going to be anti. HBE negative. Okay? We go to the window period. The window period is again, you're basically, what happens is, you get infected, the anti, the core antibodies are being produced against these antigens. The surface antigen, the envelope antigen, the HPV DNA, and the core antigen, trying to destroy these viruses. So the concentration of all of these antigens start going down, down, down, down, down, to the point where they're pretty much not even detectable. Okay, so this, thank goodness for this anti-HB, the anti-Hepatitis B core antibody, because these IgM antibodies are going to do the best they can to drop the concentration of all of these antigens down to the point where they can't even be detected. So, all of these should be negative in the window period. So now, what we're going to do here is, Hepatitis B virus, surface antigen. should be negative, thank goodness to this guy here. The hepatitis B virus E antigen should be negative, thanks to this core antibodies. And the HBV DNA should be negative or really low, okay? Next thing is you have the antibodies. The antibodies are going to be, again, thinking about this one. Your body still hasn't produced these HBS antibodies yet. You have to be cured. You have to completely recover in order to have these. So these are not going to be present in the window period. You just haven't made enough of them yet to cause any effect. So for this right here, we're going to say that the anti-HBS is negative. Okay, but look at this guy. We're switching, again, we're starting to switch over. So window period, you're going to be maybe a couple, you're probably about like a couple months in, maybe three, four months in. So by that time, your body starts switching over the production of antibodies from IgM to IgG. So you're going to have a combination of maybe both of these. So at this point in time in the window period, you're going to have anti. HBC positive, but it might be a combination of IgM, and it might be a combination of IgG. So you might have an increased total concentration of core antibodies during the window period. Okay? And again, I don't want you to worry about this one yet. We're going to worry about more for the chronic, but just for the sake of it, decrease replication, decrease infectivity. This one isn't there for about at least six to seven months as well. So don't worry about this one. The anti-HBE is negative as well. All So what happens after the window period is two things. One, is your body recovers. It produces these anti-HPS antibodies against the surface antigen and then you're completely immune to the hepatitis B virus. That's one option. You recover. The second option is that you don't produce these surface antibodies and so from that point on your body is never able to clear the virus and you have a chronic infection from that point on. And then there's one last thing that we'll talk about which is if you just get immunized for it, which you should get immunized for. So what happens? Let's go through the recovery first. So what did I tell you? In order for you to be recovered, recovery, that means that you've been cured, right? So if you're being cured, that means that the anti-HBs antibodies have been produced and that means that all of the surface antigen, the envelope antigen, and the HPV DNA should all be destroyed. That means that you have been cured, you've destroyed all of the HPV antigens, DNA, everything. So all, if you've been recovered, All of these antigens should be negative. So HB surface antigen should be negative. The hepatitis B virus envelope antigen should be negative. The HBV DNA should be negative, right? Now you're going to be cured. So now what does that mean? You've recovered, you're cured. That means that you have the anti-HBS antibodies. So you have these anti- HBV. HBS antibodies. You finally produced these guys. Thank goodness we're cured. And again, recovery. So this is after the window period. You were already producing some IgG antibodies in this window period. If you completely recover from that point on, what should you have for decades? It should all be IgG antibodies. So now all of it should switch over after you recover from that point for decades to go on. You're anti- And this is important, anti-HBC should be positive, but it should be of what flavor? IgG. Okay? And again, if you've recovered the anti-HBE in this point in time, this will also, again, I don't want you to worry about this one right now, but if you want, just actually put not applicable at this point in time. I don't want you to worry about this one. I don't want it to confuse you. I want you to focus more on the chronic with this specific antibody. Okay, so we'll take that scenario. Now, here's where you want to make sure that you understand the difference between recovery and immunized. If you've been immunized, what they do is, to give you a kind of a concept here, they take and inject you, right? So they take and inject you with a specific serum. When they inject you with this vaccine, they only inject you with the hepatitis B virus surface antigen. So what antibodies would you produce against that? you're only going to produce the anti-HBS antibodies. So the only antibodies that you're going to produce against this is going to be the anti-HBS antibodies. This doesn't have an envelope antigen. It doesn't have the core antigen in it. So you don't produce core antibodies. You don't produce envelope antibodies. The only antibody that you should be producing is the anti-HBS because that's all they give you when they inject you with this. So if they inject you, you should clear it. If you're immunized and successfully immunized, You should clear the surface antigen, right? So the HB surface antigen should be negative. And again, when they inject you with this serum, they don't even give you these E antigens, or they don't really give you any of that DNA, right? So because of that, D should also be negative. So HBV DNA should also be negative. So this is looking almost similar to recovery, right? Because again, you have to produce the antibodies against this. So that anti... HBS antibodies are going to be positive. Here's where it's different. Do you produce the core antibodies? No. Because you weren't actually exposed to the true virus which has the core antigen and the envelope antigen. So you don't actually have these core antibodies. These are negative because you haven't actually been exposed to the true virus. So the anti-HBC is negative. That is important. There is no IgG antibodies. It is IgG negative. Okay? And again, don't worry about this hepatitis, the anti-HBE antibody. I want us to more focus on this part with that. Okay? So that should cover all of this with the recovery and the immunization, understanding the difference. The last thing is, again, you don't clear the infection. So if you don't clear the infection, what does that mean? That means that all of these antigens are still going to be present. I didn't clear it. I wasn't able to get rid of the entire virus. So my surface antigen still means that I have a chronic infection. The envelope antigen, if it's chronic and I'm replicating that virus like crazy, what does that mean? That means he's positive. And again, HPV DNA, if it's replicating a lot, what does that mean? It's going to be positive. So think about it. Chronic infection. and they're replicating a lot. Okay well if I'm infected regardless of it being acute or chronic this is positive. H, B, S, A, G is positive. If there's increased replication and increased infectivity, well this is the replicate of chronic infection, then that's super positive. Right? Next thing is if I go to the HBV DNA, and that means, oh, this is the replicative chronic infection. That's increased. That means that this is going to be super positive. So HBV DNA is going to be positive and increased, pretty high, right? Now, think about the antibodies. Anti-HBS, were you able to produce this? No, because you weren't cured. You're still chronically infected. So that means that there is no anti-HBS antibody. It's negative. Were you able to produce the core antibodies? Yeah, you're going to produce those because your body's going to do the best that it can to clear the infection, but it's not going to be enough. You've got to remember, this guy, he does his best. He's a workhorse. He's going to try to decrease those antigens as much as he can, but he can't do it on its own. He needs this guy to completely cure you. But he's going to do his best. So he is going to be produced, but if it's a chronic infection, which one is it? M or G? It's G, right? It should be anti. HBC positive, but of what flavor? IgG positive. Now this guy comes into play. If anti-HBE, this antibody is produced more specifically in chronic infections, because it's like after about six months before this guy's being produced. So now... If this guy is actually being produced that means that it's decreasing replication, it's decreasing infectivity. Is it? No, this is a chronic infection that's replicating like crazy. So what does that mean? That means this guy is negative because he's not being produced in a high enough amount to oppose these antigens. So the anti-HBE is negative. We come to the last one, chronic infection. If you're infected no matter what, you have the surface antigen. So that's positive. If you have a non-replicating infection, go to the envelope antigen. It's only really positive whenever you're replicating and you're infecting other cells. Well, is that replicative? No, it's non-replicative. So what should this mean for the envelope antigen? That means it should be negative or decreased, right? So we say that the envelope antigen is going to be, in this case, negative or super decreased. HBV DNA. So this is going to be specifically positive or high whenever it's increasing replication, increasing infectivity. Well, this is non-replicative. So what does that mean? That means it should be decreased or not detectable. So HBV DNA should be negative. Antibodies. We have a chronic infection. You only have this antibody if you're cured. So do you have it? No. So you don't have this because you haven't been cured. So anti-HBS is negative. Anti-HBC. Do you produce this antibody? Well it's a chronic infection. Your body's going to try to clear the infection. It's going to do the best it can. It might do it pretty darn well, not bad, but it should be there, right? So this should be there in a chronic infection because you were exposed to it. And so you should have anti- HBC antibodies but again this is a chronic infection so that's IgG antibodies so it should be IgG positive antibodies last thing this isn't more specific for chronic infections this is the envelope antibody if it is positive that means that there's decreased replication and decrease infectivity that means that it's not replicating should it be positive yes so that's why I wanted us to focus more for the chronic infection so again this is going to be anti HB e antibody positive and again that should be indicative that you had a chronic infection but you're not replicating you're pretty much trying to keep the virus dormant alright so this pretty much look at this we cover all of this this is pretty much everything that we just did was focusing primarily on the HBV sirology okay so all of these ones that we just covered is for HBV the next one we're gonna go ahead and do is the hepatitis C virus serology All right, so the next thing that we're going to cover is hepatitis C because it can also cause chronic hepatitis. And we should be able to, again, know what specific state they're in, if they have an infection, if it's acute, if they cleared it, if it's a chronic infection. And then we'll talk about how we can determine the degree of fibrosis, another thing that we can talk about. All right, so first thing for hepatitis C virus. One of the things that you start off with, so we're going to talk about HCV, right? First thing you do is you check their blood for an antibody. Okay, so we call it anti. HCV antibodies. And again, if you guys really want to remember, this is of the IgG type. So the first thing you do is you check the anti-HCV antibodies. If these are positive, so let's say that these are positive, the second step is you then check and you do PCR. So you run a PCR. of their HCV RNA. Okay, so then you're gonna run their blood and they're gonna check to see if the HCV RNA is positive. If the HCV RNA is positive, so we'll say over here it's positive, then that means that the patient is infected. Okay, they're infected with the hepatitis C virus. If it's negative, that means that they cleared the virus. Okay, so that means that they cleared the virus. They cleared the virus. Here's the next thing that we have to understand. Once we check the HCV RNA and if it's positive, we want to determine how long it's been positive. If it's been positive for less than six months, then this is acute. Acute. But if it's positive for greater than six months, then this is actually going to be chronic. And that's why this is important. So the first thing you do is you check the antibodies against the hepatitis C virus, particularly IgG, because this is a chronic infection. So it's going to take some time, your body's going to produce antibodies against it. If that's positive, then you know that the patient is going to have been exposed to it in some way, so check to see their hepatitis C virus RNA. You do the PCR of it. If it's positive and if it's been positive for less than six months, it's an acute infection. If it's been positive for greater than six months, it's a chronic infection. And if it's negative, that means that they've cleared the virus somehow. All right, so now once we've done that, if the patient has a chronic infection, so if they're positive for this HCV RNA when they do this PCR test, polymerase chain reaction, and it's greater than six months, we should then do something else. You have three options, really. One thing that you can do is, and we'll mention it here because I want to make sure that I tell you guys. One option is you can do a liver biopsy. Obviously this is invasive. Okay, and it has its risks. The second thing that you can do is what's called a fibrosure test. Okay. Problem is with this test is it is fricking buku bucks. Okay. So it costs tons of money. I think it's like $300, uh, just to run this test. So pretty expensive. So one of the things that you can do to, obviously this is invasive and that poses risk. This is super expensive, but again, these tests are much better. This would give you a definitive diagnosis of fibrosis, and this will give you a pretty high sensitivity or specificity of fibrosis. But there's another way that you can do this. You can look at their blood work, right? And you can use what's called the APRI score, which is the AST to platelet ratio index. Okay? And you can get a percentage. Now, what the APRI score is, is you take the patient's... AST level, right? You divide that patient's AST level by the AST standard in that lab, okay? So then from there, I'm going to divide this number that I get from the patient's AST divided by the AST standard by the number of platelets, okay? And then I'm going to multiply this whole thing here. Let me put this here. I'm going to multiply this whole thing by 100, And that's going to give me my apri percentage. Now, usually, if the apri is greater than, we say like 1.5, that means that there is a significant amount of fibrosis. And again, you might say this as a preliminary test to going in to do a liver biopsy and you want to confirm, you say, oh, their APRI score is greater than 1.5. We should do a liver biopsy then and check. And so this can be kind of a preliminary thing that you can do without having to spend a ton of money or put the patient underneath an invasive procedure. So again, this is something that you should do if the patient does have hepatitis C virus and it's a chronic infection that you've proved through this algorithm. You should do either a liver biopsy if you want to. The Fibersure test, which is going to be a better test than the Apri, or you can do the Apri, which gives you a kind of an idea of how much fibrosis there is. And then you can follow up if you need to with the Fibersure test or definitive diagnosis like a liver biopsy. So again, that covers our HCV serology for this one. The next thing that I want to go over is I want to go over the HDV serology. If you guys remember, we said the HDV, it needs HBV in order for the patient to have this diagnosis of HDV. So before you can even do this, you need to make sure that they're HBV positive. If they're HBV positive, then you go ahead and you do the panel for the HDV. So first thing you do is, if the patient has this type of infection, right? So they've been exposed to this acutely. So this is going to be the acute point. So let's say that this is acute infection, okay? What you're going to know is that the antigen is specifically going to be the HDV RNA. That's the antigen. And then the antibody, depending on if it's in the acute period, it should be an anti-HDV. So it should be some type of IgM or IgG antibody. If it's acute, it should be IgM. So, if the patient is infected, they have an acute infection, there should be positive HDV RNA. That should be positive. That means that they have an acute infection. And then on top of that, the antibodies against this HDV should be IgM. So you should have IgM positive antibodies directed against the HDV virus. Okay? That's important. There is another thing that you can do for the acute one. They say that if someone does have acute infection and you measure their blood, if they have a hepatitis D virus antigen, that can be positive in the acute and it's never positive in the chronic. The reason why is it gets cleared quick. Okay? So that's another thing that can help you with the diagnosis. The last thing is chronic. So if it's chronic HDV, you've been infected, right? So you've been infected by the virus, so you're still going to have this HDV RNA. So HDV RNA is still positive. The HD antigen should be negative because you should have cleared it by now. and the antibody should have switched, right? So you should switch from IgM in an acute phase to IgG in the chronic phase. So it should be IgG positive antibodies, okay? So it's a very simple thing to understand HDV serology. So again, first thing, confirm that the patient is infected with HBV. Then if you find that whenever you run their blood and it comes back IgM antibody positive with HDV RNA positive and HD antigen, That means that there's an acute infection. If you run it and they're IgG positive, their HD antigen is negative, and their HD of the RNA is positive, you know it's a chronic infection. Just to give you a little bit of information, just so you don't read something and get confused, sometimes the hepatitis D antigen can also be negative in an acute phase. It just depends how, when you measure it. If you measure it early in the acute infection, it should be positive, but if you measure it a little bit later. it might be negative still while they're acutely infected. So that's important to remember. It can be positive or negative depending on what stage of the acute infection they're in. Okay? So that covers HDV. Let's move on to the next one. All right, so the next one that we want to talk about is the hepatitis A virus. So we're going to be focusing on the hepatitis A virus here. All So hepatitis A virus. Now. When we get into this one, again, we're going to talk about an acute infection and if they've been, we could also look at their past exposure or if they're immunized. There is an actual vaccine for hepatitis A virus, hepatitis B virus. Okay. And that's important to remember that. So hepatitis B virus, hepatitis A virus. And technically, if you think about it, if you prevent someone from having hepatitis B, you prevent them from having hepatitis D. The only hepatitis is that the virus is. that do not have a vaccine against is hepatitis E and hepatitis C. So that's important to remember. But hepatitis A, you do. So let's say if someone's acutely infected. If they're acutely infected, you can check their blood or you can check their stool. And what should come up if they're acutely infected is HAV RNA. That should be positive, right? If they're acutely infected. And the antibody that you should produce against this HIV virus should be IgM. That's indicative of an acute infection. Pretty simple, right? Past exposure. So in other words, you've been past, you've been exposed to this, your body's developed antibodies that switched over the antibody from IgM to IgG. So antibodies after past exposure or you've been immunized, so you've been given the vaccine and your body's produced antibodies against that vaccine, particularly similar to the HIV virus, you should have IgG positive antibodies. and if you've ridden the body of it, you've been past exposure and you've cleared it, or you've been immunized, you should not have the HAV RNA present. It should be negative, non-detectable. So again, if you've cleared the virus or you've been immunized, you shouldn't have the RNA positive or detectable, and you should have IgG antibodies against that virus. If it's acute, you have IgM, and if you're still infected with it, you can do the stool or blood and check the HAV RNA. and that'll also be positive okay that covers this one the last one that I want us to talk about here is the hepatitis E virus I didn't mention this when we talked about the type of viruses but here's one of the things that I also want to add on to the hepatitis E virus it is also going to cause acute infections and again these are transmitted fecal oral route The patients that you have to be super careful with who have hepatitis E virus is pregnancy. So I just want to make sure I mention this as a note because this is a common question. You see this all the time. If patients who are pregnant and they have hepatitis E virus, let's say that their hepatitis E virus positive, they're pregnant. The reason why this is so dangerous is it increases their risk of what's called fulminant. hepatitis. In other words, they're like full-blown liver failure and they're at risk for death because you're going to have to give them a liver transplant. So I just wanted to make sure I mentioned this because this is a common test question that you can see and it's also something you should be aware of in clinical practice. Someone has hepatitis E virus, the mortality and morbidities of it increase especially if the patient is pregnant. Okay, so now that I've done the little pep talk there, the next thing that you need to know is... Hepatitis E virus, it only really causes acute infections. Again, we said that there's rare occurrences with someone's immunocompromised that it can cause chronic infections. We're not going to really talk about that. So acutely infected. If you're acutely infected, you take the patient's blood, right? You run this viral panel. You know that if they're acutely infected, the HAV RNA should be positive. and your body is going to try to produce antibodies against this this hepatitis E virus what are those antibodies in the acute phase it should be IgM positive right it's pretty simple past exposure now if you've been cured right so in other words let's say that past exposure we can say more specifically you cleared the virus right you got rid of the virus in other words it took its course it caused the infection you rated it from the body That means that the HAV RNA should be gone. It should be negative. You've been exposed in the past, but you've cleared it. Okay? That should be negative. The antibody here, which is very interesting, is whenever you've been past exposed, there is IgG antibodies. They can be positive, but here's the thing. It only lasts, usually, these can last for decades. This only lasts for maybe two to three years and then their concentration drops. Okay, so why is that important? You're really not going to, if you're looking at this like five years, 10 years later, this IgG antibody, it's probably going to be negative. So I want to make sure that I put here, it could be positive or it could be negative. It just depends upon how long after they've been exposed to the virus that you decide to run this panel because it only can persist for a couple of years. So what do you do then? You just run the HEV RNA. If the HEV RNA is positive, That means that for some reason they might be immunocompromised and they do still have the infection. Okay, so that's important to remember. IgG antibodies aren't going to clue you in to tell you if the patient has past exposure, especially if it's after like three years. Okay, so that's important to remember. Acute infection, HEV RNA is positive and you're going to have the IgM antibody. If it's a past exposure and you look at this and you've cleared the infection, The HEV RNA should be negative. If you haven't cleared the infection for some reason, like you're immunocompromised, that HEV RNA will still be positive. But again, the IgG antibodies, they could be positive, but they only persist for a couple years. That's important to remember. So they might be gone whenever you check it later. So that covers the hepatitis E virus serology. Alright Ninja Nerds, in this video we covered the serology of the hepatitis viruses, particularly A, B, C, D, and E. We went into great detail. I hope it makes sense. I hope you guys did understand it. If you guys did, hit that like button, comment down in the comment section, and please subscribe. Subscribe! Alright? As always guys, if you guys go down in the description box, we'll have links to our Facebook, our Instagram, and even our Patreon account. If you guys want to donate even a dollar, we would truly appreciate it. But as always Ninja Nerds, we love you and until next time.