[Music] all right ninjas 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 and get started on that all right 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 with 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 of the 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 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's 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 okay 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 and 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 had 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 okay so we don't actually measure this we measure an antibody against it but i just want you to measure know that it's not measured okay 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 h b s 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 they in other words they actually were able to produce the antibodies and completely get rid of the virus or they were vaccinated against it okay 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 the antibodies that are against the core antigen if these are positive they can be in two types you can have i g m which that just means that it's acute or it can be i g g 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 hb e 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 increase replication and increase infectivity okay all right 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 antibodies on the other side talking about these and what 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 patients have been infected acutely what happens to the surface antigen is a positive or negative well they've been infected so the hb um the hepatitis b surface antigen should be positive that's a simple concept 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 the simple thing again we don't look at the core antigen but we do look at the hpv dna so again hbv dna is going to be positive okay go into 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 hbc's 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 particular these aren't produced until the more chronic areas so after the patient's either completely resolve the infection or if they have a chronic infection okay but this is again more particularly free they're 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 h b e 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 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 antibiotics 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 uh core antibodies and the hbv dna should be negative or really low okay next thing is you have the antibodies right 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 about 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 gonna 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 hb e is negative as well all right so what happens after the window period is two things one is your body recovers it produces these anti-hbs 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 hbs antibodies you finally produce 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 the for decades it should all be igg antibodies so now all of it should switch over after you've recovered from that point for decades to go on your 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 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 these should also be negative so hpv 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 didn't you weren't actually exposed to the true virus which has 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 increase 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 replicate of 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 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 so 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 it'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 a 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 in decreased or not detectable so hbv dna should be negative antibodies we have a chronic infection you only have this antibody of your cure 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 is 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 is a 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 b 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 all right so this pretty much look at this we covered all of this this is pretty much everything that we just did was focusing primarily on the hbv serology okay so all of these ones that we just covered is for hbv the next one we're going to go ahead and do is the hepatitis c virus serology all right so the next one 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 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 let's 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 i g g 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 going to run their blood and they're going to check to see if the hcv rna is positive if the hcv rna is positive so let's 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 is 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 is and we'll mention it here because i want to make sure that i 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 freaking 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 because 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 app rescore which is the ast to platelet ratio index okay and you can get a percentage now what the app rescore 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 num 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 a hundred and that's going to give me my apri percentage now usually if the opry 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 approach scores greater than 1.5 we should do a liver biopsy then in 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 fiber sure test which is going to be a better test than the opry or you can do the opry 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 fiber sure 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 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 is that the antigen is specifically going to be the hdv rna okay that's the antigen and then the antibody depending if it's in the acute period it should be a anti hdv right 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 i g m 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 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 hdv right 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 hd vrna 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 hpv 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 hdv 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 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 the 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 this is we're going to be focusing on the hepatitis a virus here right 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 ex we could also look at their past exposure or if they're immunized there is an actual um a 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 viruses 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 cutely 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 h a v 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 it's 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 ig g 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 okay 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 so 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 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 when 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 the 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 gonna if you're looking at this like five years ten 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 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 have 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 gonna 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 okay 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 iron engineers in this video so 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 all right as always guys if you guys go down 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 engineers we love you and until next time [Music] you