Okay, thank you for having me at this course. So this is between you and lunch, hopefully you can bear with me. So hepatitis B, it's not very common in the United States, but it's actually more common than you think, and certainly it's still a major problem worldwide. These are my disclosures. Whenever we talk about hepatitis B, one of the most confusing things is all the different tests. What do they all mean? So I'm going to go through some of the very basic things, interpretation of the tests, indications for treatment, and a choice of therapy, and I was specifically asked to also address hepatitis B reactivation. So this is what I propose when a patient with hepatitis B is referred to you. This would be someone who tests positive for hepatitis B surface antigen. As normal, you would take a history, but it's very important to take a family history as well. The family history would include the parents, the siblings, the spouse, a significant other sexual partner, and the children, both in terms of trying to figure out the source of infection, as well as I'm trying to make sure that all the family members have been vaccinated and prevented, and also to find out if there's been a family history of XCC as well. We then proceed to a physical examination, which in most instances is going to be negative until the patients get to advanced stages of cirrhosis. As far as lab tests is concerned, there are really several categories that we consider. The first thing is the virus replication. Here, you're thinking about testing for e-antigen, anti-e-antibody, and hepatitis B virus DNA. It is also important to make sure that you rule out co-infection with hepatitis C, Delta, as well as HIV. And consider other causes of liver disease, and increasingly, hepatitis B and Nafl go hand in hand. Even for your skinny Asian, many of them could have concomitant fatty liver. So think about that. Then we assess liver disease severity. In the past, we relied on liver biopsy, but most of the time, we start with liver chemistry, we get blood counts, platelet count is very valuable in assessing liver disease. Dropping platelet count signifies cirrhosis portal hypertension, albumin bilirubin protein tends to be normal until very late stages. First time I see the patient, I usually get an ultrasound, gives me a good idea whether they have cirrhosis or not, portal hypertension, and subsequently, in patients who need XTC surveillance, that's certainly something that we'll continue to do. As I've mentioned in the past, we rely on liver biopsy, but increasingly, non-invasive assessment, certainly fibro scan. But you can also rely on liver testing, APRI, FIFOR, but bear in mind that when the patients are from high AST and ALT, those markers become not very valuable. Think about checking for hepatitis A status and vaccinating the patient against hepatitis A, and counseling on precautions to prevent transmission of infection, alcohol use, and healthy lifestyle. So these are the serological markers of hepatitis B infection. The hallmark for hepatitis B infection is hepatitis B surface antigen. When it's present, the patient has infection, but you need to do the IgM core antibody testing to differentiate acute versus chronic infection. Ye antigen being present usually indicates earlier stage of infection, high level of virus replication. Anti-Ye, the reverse, later stage, lower level of virus replication, but not necessarily none. Surface antibodies is a sign of immunity, which can be acquired through vaccination if it is present alone. But if it is present in association of core antibody, that's recovery from past infection. Patients of chronic infection will be surface antigen positive, and core antibody, which is the IgG positive. When we talk about screening for hepatitis B infection, we would usually test for surface antigen as well as surface antibody. And you might consider testing for core antibody as well. Another way of looking at these testing would be to put them together. So if you have multiple test results, negative for everything, not being exposed, surface antigen positive, total core antibody positive, some of chronic infection. Surface antigen positive, IgM core antibody positive, some of acute infection. Someone who's only surface antibody positive, immunity from past, surface antibody positive together with core antibody positive, that's immunity from past infection. Surface antibody positive alone, that's immunity from vaccination. Now we see from time to time, about 5 to 10% of US population are just core antibody positive. No surface antibody, no surface antigen. So what does that really mean? Well, a majority of these patients, they actually had the past hepatitis B infection with spontaneous loss of surface antigen. This is particularly true for people who come from endemic areas, like from Asia, from Africa. People with risk factors for hepatitis B, like people with hepatitis C infection, people with HIV infection. If you test them for HPV DNA in the blood, it's usually not detectable. But if you look at the liver tissue, hepatitis B virus DNA is usually present, and therefore when you immunosuppress them, there's still a risk of HPV reactivation. Let me now briefly discuss about treatment. You all know that these are the proof treatments, interferon, which we rarely use for hepatitis B, with multiple oral antivirals. But essentially, we would only be using antacovir or one of the formulations of tenofovir. We don't want to use the others because they're less potent and there's a high risk of drug resistance. Unlike hepatitis C, where we can talk about cure, eradication, with hepatitis B, we're talking about suppressive treatment. So we suppress the virus replication, we push the virus into a corner. But when we stop pushing, the virus can bounce back. And that's the reason why we're not at this stage recommending treat all, because you have to be willing to commit the patient to very long durations of treatment. In deciding whether we should recommend treatment now, or whether we would monitor the patient and consider treatment at a later stage, much depends on how bad is the liver disease at this time. Patients come to you with decompensated cirrhosis and ascites, no-brainer. Put them on treatment now. Patients of compensated cirrhosis, even if the virus level is not very high, I would recommend putting them on treatment. But the bulk of the patients that come to us don't yet have cirrhosis. And that's where we have to debate. Treat now or watch. And that's based on predicted risk of what the outcome would be. So these are the ASLD guidelines. At the bottom, cirrhosis patients, go ahead and treat. The patients of no cirrhosis, antigen-positive, if they're in the early immune-tolerant phase. These are the patients who are antigen-positive, very high DNA normal liver enzymes. They tend to be the young patients, particularly young Asians. At this stage, we're not recommending treatment unless they're no longer young. So no longer young could be more than 30. No longer young could be more than 40. Because these people who have maintained very high level virus for three, four decades, we start getting really worried about them and would recommend treatment. Certainly if they're in the third trimester of pregnancy, we want to put them on antiviral therapy, reduce the virus load, further reduce mother-to-child transmission. The patients who are in the immune-active stage, antigen-positive, DNA more than 20,000, elevated ALT, we recommend treatment. For e-antigen-negative patients, if they're inactive carriers, e-antigen-negative, very low DNA, less than 2,000, normal liver enzymes, we would not recommend treatment. But sometimes it's not easy to differentiate a e-antigen-negative patient. It's a truly inactive carrier or it's just fluctuating e-negative chronic hepatitis B. I just happen to catch the patients when the liver enzymes and the virus level are lower. So if you're not certain, you need to monitor the patient, get two, three sets of lab results to figure it out. Now the Asian studies show that if you do quantitative S, and the quantitative S is very low, there's a higher chance that they're inactive carriers. But the quantitative S is not readily available, although there's some reference labs to offer those tests. So this is a depiction of the natural history of chronic hepatitis B. As I've discussed in the non-sterotics, treatment's recommended for the two green boxes, the e-antigen-positive active disease and the e-antigen-negative active disease. And for those in the inactive stage, we'll just be watching them. Now watching them does not mean forget about them, tell them that they're nothing to worry about and come back only when you're dying, okay? Watching means following them, getting testing, because over time, sometime in the future, the virus can become more active, disease can become more active, and that's when you jump in and start putting them on treatment. Choice of treatment. I've mentioned there's interferon, there's oral antiviral. So obviously, when you offer this choices to your patients, the patients prefer to take a pill than to take injections. Interferon, the advantage is that it's a finite duration. We treat them for 12 months, and then we see whether it works. If it works, great. If it doesn't work, we'll have to consider putting them on oral treatment. It's not as strong with antiviral activity, but it actually leads to a higher rate of the antigen loss and S-antigen loss. We don't need to worry about resistance and variance, but a big problem is all these side effects. And the young people have not used interferon, they don't even know what side effects. You actually make the patient sicker than the disease itself. Now the oral antivirals are simple, one pill once a day, but because it doesn't actually get rid of the virus, it just push the virus in the corner, and it has a very low rate of the antigen loss and S-antigen loss, you're committing most of these patients to many years or sometimes lifelong treatment. We used to worry about drug resistance variance, but with antacovir and tenofovir, that risk is extremely low. Side effects are, generally speaking, very minimal. But adenovir, which we no longer use, and tenofovir, DF, does cause a very low risk of renal as well as bone toxicity. And that's why there's a new formulation of tenofovir called TEF, tenofovir elephantimide. This is improved from drug delivery to hepatocytes, therefore you get less systemic exposure. So the kidneys and the bones are less exposed. You actually use a lower dose, 25 milligram instead of 300 milligram. And the comparison studies, so the blue line is TDF and the black line is TEF, so you can see that the drop in bone mineral density is less, as well as the drop in GFR is less. But you can also, so you say, well, my patient's insurance doesn't approve of the use of TEF. So is my patient gonna get, am I killing my patient by causing kidney failure? No, I mean, it is, it can cause side effect, but it's not a major common side effect, particularly with younger patients. Are they equally effective? Yes. So this is a study where TEF is directly compared to TDF, and you can see that both in terms of DNA suppression, E antigen loss, as well as S antigen loss and LT normalization, they're very comparable. So now I'm gonna move on to reactivation of hepatitis B replication, which is something that unfortunately still happens. What does it mean? It means that when the patients are immunosuppressed, the virus replication goes up. So how do we define that? To some extent, it depends on whether you have baseline DNA. If you have baseline DNA, the ASLD guidelines say that two log increase, which is a hundredfold increase, that's for sure that this is a real change. Now what if the patient does not have DNA detectable baseline? If it goes up to 100, does it really mean that this is reactivation? Maybe. But we said it, more than 1,000, for sure it is. Unfortunately, many of these patients do not have baseline testing. So I have no idea. It could be 1,000 before, it could be 10,000 before. So we said in that case, if it's more than 10,000, we really are worried. As I've mentioned, you can also see reactivation in patients who were previously surface antigen negative core antibody positive. And how would we know? Well, if they now become surface antigen positive, or if now you can find that HPV DNA become positive in the blood. If it were just a virus going up, you say, who cares? Well, you care, because the ALT can go up. And these patients can actually go into liver failure. They can become jaundiced. They can die. I personally have witnessed several of these deaths. And they're all preventable death if we think about it. So when you see ALT go up, you see signs of liver failure in the presence of increasing HPV replication, then you can attribute that. Bear in mind that in patients with cancer receiving chemotherapy, ALT can go up for many reasons, drug toxicity, sepsis. So you have to have concomitant evidence of virus replication. So this is a graphical depiction. What happens is you usually see the virus replication go up first before the liver enzymes go up. And of course, oncologists don't monitor HPV DNA. So they won't know until the liver enzymes go up. And sometimes when the liver enzymes go up, they blame it on those toxic drugs. They're not thinking about it until the patient's obviously jaundiced with a scientist, and they call you in panic. Can you see the patient within the next two hours? So we talk about oncology setting, but it's not just in patients of cancer. And we tend to think more about patients of leukemia, lymphoma. But solid tumors can also be the problem. And it's not just cancer. Even HCC receiving TACE, there are reports because although the chemotherapy goes directly to the liver, some of that gets spilled into the systemic circulation also. And it's not just cancer drugs because there are all these biologics, anti-TNF, anti-CD20, long-term steroids. They all can cause reactivation. And also, as you know, patients of hepatitis C receiving DAA therapy, there's also risk of hepatitis B reactivation. Patients co-infected with HIV and hepatitis B, when they receive antiretroviral that suppress both virus, and all of a sudden someone is not thinking, change the treatment so that they're only on drugs that suppress HIV but not hepatitis B, that can also cause reactivation. So any change in drugs need to be thinking about. As I've mentioned, you think about the clinical setting, you think about the type of drugs, the chemotherapy, antibodies that block B cell functions, particularly rituximab, for example, corticosteroids, a lot of the biologics. Some of the molecular target agents have also been reported to cause HPV reactivation and certainly anti-rejection therapy to prevent rejection for liver transplant, kidney transplant, heart and lung transplant. But oftentimes what we forget is when our colleagues consult us, you review the treatment plan and you say, oh, it's fine, particularly for service antigen-negative core antibody positive patients, the initial treatment is fine, but remember, many of these patients receive combination of immunosuppressive drugs. So when you think about one drug, maybe it's okay, but the whole regimen may not be okay. The regimen is okay today, but three months later they say, oh, the treatment is not working, so now they intensify the treatment and now it's not okay. And these new drugs keep coming up. We can't keep up with all these new oncology drugs, all these new biologics. And a lot of these drugs, when they're going through clinical trials, they exclude everyone who tests positive for hepatitis B, so there's no data. Well, there's no data to show that it can cause reactivation. It doesn't mean that it cannot. So we've got to be very vigilant. So how common does reactivation occur? These are old studies. For hepatitis B service antigen-positive patients, if they have hematological malignancy, it can be as high as 30, 40% with reactivation associated with hepatitis, liver failure in about 10%, and death in about 5%. The good news is that if you give them prophylactic antiviral, you can prevent it, and it's pretty effective. In about 80% to 100% of patients, you can prevent the reactivation, the hepatitis-associated death, and you can even improve cancer-related mortality. Why? Because when you have reactivation and transaminases go up to 500, the oncologists freak out. They say, oh no, we have to stop the cancer treatment. And it may take four months for everything to subside, so the patient's cancer is not getting treated. So if you prevent reactivation, you actually allow the cancer therapy to proceed. Now prophylactic therapy means that you start the antiviral at the same time as you start the immunosuppressive therapy or before, whereas therapeutic antiviral, that's really when you see signs of DNA going up, when you see signs of ALT going up. So you're now doing catch-up. So as you would expect, catch-up is not as effective as prevention in preventing reactivation, hepatitis flare, and even liver failure. So what are the risk factors? Literature shows that males, older age, hematological malignancies, the intensity of the immunosuppression, more drugs you throw at the patient, more you suppress the immune system, rituximab is a bad player, and certainly surface antigen positive patients, higher risk than the surface antigen negative core antibody positive patients, higher pre-treatment HPV DNA, higher risk. So I want to focus on the surface energy negative core antibody positive patients because that gets less attention. Some people said, well, let's just uncheck HPV DNA prior to immunosuppressive therapy. If the DNA is not detectable, I'm fine, right? No, because the DNA may not be detectable initially, but once you immunosuppressive DNA, it can become detectable. So as you can see, the gray bar undetectable DNA at presentation, there's still a risk of reactivation. Lower risk, but not zero. Similarly, the core antibody positive patients with surface antibody, lower risk, but not completely. So these are the people with surface antibody, lower risk, but not completely protected. How can we risk stratify? Well, anti-CD20 is bad if you have hematological malignancy, require bone marrow transplants, stem cell transplants, high dose steroid is bad, and you go through that list. But as I've mentioned, you have to look at the entire regimen and also keep monitoring because the regimen can change over time. So what's the ASLD recommendation? All the patients should be screened for surface energy and core antibody prior to immunosuppressive or cytotoxic therapies. Surface energy and positive patients, we recommend prophylaxis. Surface energy negative, core antibody positive, it depends on the setting. If they need bone marrow transplant, they need rituximab, ProFlex. Other patients you can monitor. And when ProFlex is indicated, start as soon as you can and continue for at least six months after stopping immunosuppressive therapy. But for anti-CD20, continue for at least one year. And preferably use Entacavir or one of these Tenofovir. So quickly, just to finish, Hep-C. Everyone know about the warning. So how common is it? It is common in surface energy and positive patients, reactivation in a quarter. But actually, associated hepatitis is not as common. In surface energy negative, core antibody positive patients, the risk is actually very low. And therefore, the ASLD recommendation would be, yes, screen for surface energy and core antibody. But ProFlex only for surface energy and positive patients with detectable DNA, with indications for hepatitis B treatment. And for surface energy negative, core antibody positive patients, we can monitor the ALT. As you treat hepatitis C, you expect the ALT to improve. But if you see that ALT is actually going up while the XCB RNA becomes undetectable, that's when you need to be worried about reactivation. So coming back to the case that Amanda gave me, 42-year-old women, injection drug use until two years ago, completed Hep-C treatment a year ago with SVR. Now all of a sudden come with high ALT. So what happened? Well, obviously you worry about acute hepatitis, but think about DILI as well. If this is some hepatitis A, you will be checking for IgM hepatitis A antibody. It could be acute hepatitis B when you'll be testing for surface antigen, IgM core antibody, and perhaps throwing in HPV DNA as well. Could this be reactivation by DA? But that's a year ago, so very unlikely. Could this be Hep-C re-infection or relapse? Well, relapse would be unlikely because it's a year out, but re-infection potentially. So you'll be checking for HCV RNA and not the Hep-C antibody. So in this case, the patient was surface antigen positive, IgM core antibody positive with high virus flow, HCV RNA not detectable, so this is likely acute HPV infection. And you have to ask yourself, what did I not do? Had I offered Hep-B vaccination, this might not have occurred. So always remember to check immune status and vaccinate. Thank you. We're going to go ahead and move on to our panel discussion. So you're welcome to come forward if you have any questions to the microphones. I'm going to start off with a question. This is for Caitlin and Dr. Harnoy. You mentioned there's some crossover between selecting patients for TAIS and TAIS. You mentioned portal vein thrombosis being contraindicated for TAIS, but are there other characteristics that you would consider one over the other? I think overall, hepatic function becomes important in terms of looking at that. So as was stated, that's more looking at the degree to which they've had decompensation, what their synthetic function really looks like it is. And really, this is very institutional dependent, and I think we've gotten more biased. I think other institutions wouldn't necessarily take the same approach, but we've been more and more deferring to the radioembolization in those patients, particularly with more marginal liver function. I don't know if within your institutions you've... We're still doing more TAIS than TAIR, but I agree that some institute is 100% TAIR, and some institute is 100% TAIS. We use both, but I would say that TAIS outnumber TAIR. I just want to echo, I think every institution, it's like their immunosuppressor protocol. It's what they believe. The religion. Yes. Yes. Hello, Dr. Locke, I have a question for you based on a patient I just have been seeing. He developed, he was in the hospital several months ago, actually shortness of breath. They diagnosed him with idiopathic pulmonary fibrosis, and in the meantime, they noticed his liver enzymes are elevated. Well, it turns out he has acute hepatitis B in his 60s, and he came to me just to be followed up. At first, we were going to follow him, because to see if he got an acute phase. Pulmonary's starting to get nervous, they want to give him steroids to treat his lung disease. It's okay, give me a month, let's see what his trend is. Viral low's 90 million, liver enzymes in the 200s, all right, we'll put him on treatment. Put him on Takovir, and his numbers came down nicely, but just within three weeks, but he's not viral zero, and his liver enzymes are still somewhat elevated. Do we give them the go-ahead to start steroids? When is the time I can say, yep, you can start them now, and do we, okay, because we're on the antiviral, or do we have to wait until he clears? Well, so the first thing is, normally we would not be recommending treatment of acute hepatitis B, because majority of these patients are going to get over it. Although, acute viral hepatitis in older people, and unfortunately I will be in the older category, because it has a higher mortality, both for acute A, acute B, and if this patient weren't getting IPF and need immunosuppressive therapy, you might be watching, as long as he's not showing signs of liver failure. But if he has IPF, and the pulmonary people say, look, I mean, how long do you guys want to wait? This guy cannot breathe. Sometimes you just have to balance the benefit against the risk, so in this case, you want to treat his lungs, they need the steroid. I would, sort of, if the viral low, after a couple of weeks of watching, this acute hepatitis is not quickly going away, which I'm not surprised in older people, it just lasts longer. I'll just start the antiviral, and worry about it later on. Do I need to continue the antiviral? Because if this is truly acute hepatitis B, after a while, the patient might seroconvert from S antigen to S antibody. That tells you that you don't need to keep the antiviral forever and ever. I guess my question more is, he's on the antiviral, and can they start the steroids, even though he's not completely responding? So you don't necessarily need to wait for the DNA to be undetectable, because you have to balance. It's the same thing with oncologists. Okay, start off with millions and millions, how low do I need to bring it down to? If you have the luxury of waiting, you want to see that it has dropped. Usually the virus, when you start antiviral therapy, the first phase drops very quickly, and then it's very slow phase. It gets down to the 100,000s, tens of thousands, and not the tens of millions, makes you feel more comfortable. Thank you. Hi, thank you everyone. This question is for Dr. Locke. Obviously in the setting of liver transplant, we give lifelong prophylaxis for the hep B core antibody positive livers, but in the recipient, when the recipient is hepatitis B core antibody positive, antigen negative, surface antibody positive, do you still give lifelong prophylaxis? Because I've worked, and hep B was not their underlying, so I've worked with surgeons and hepatologists alike that did not find it necessary to give prophy. So the recipient is core antibody positive, and is getting a liver from a donor, whose surface antigen negative, core antibody negative. I would not need to give prophylaxis antiviral, because that liver of the recipient has the virus, but I've thrown that away. I've put in a nice clean liver into this recipient, so I'm fine. But if I take a liver from a core positive donor, that's different, because now I'm putting in a liver with virus into this recipient. And then one more question if I could. Do you find it necessary, I know that if a patient is core antibody positive, surface antigen and surface antibody negative, do you still vaccinate those patients? So it's entirely up to you. There is no harm, okay? If you're not sure, in most instances, these people have past hepatitis B infection, they cleared a surface antigen, and the vaccination, they're not going to respond to it. But if you're not sure, and you want to give the patient a benefit of doubt, there's no harm. You give them the vaccination, if you were wrong, and they developed the immunity, that's great for them. If they didn't develop the immunity, it would cause no harm. Thank you. My name is Prabhu, I'm an epidemiologist with the LA County Department of Public Health, and had a question related to the last case, and it's a common situation we see, which is we get core IgMs that are reported to us, and I'm always wondering, how often is this an acute hepatitis B versus someone who's just undiagnosed and happens to present for the first time with a flare? And wondering if you can answer, when you see a core IgM, how often would you say it's likely an acute infection as opposed to a new presentation of a flare, and or what clues would you use to try to help you sort that out? Very good question, because although classical textbooks, we say the IgM core antibody positive indicates acute infection. When you have a severe flare of underlying chronic hepatitis B, the IgM core can become positive. Now, mild flare with the transaminases going from 50 to 200, the IgM core is not going to be positive. But when the ALT is more than 1,000, the IgM core can become positive, and it can be very confusing. Is this acute B or someone with chronic B, not diagnosed, and now presenting with a massive flare? We ask the epidemiologists, go do some detectives on story. What are the risk factors? Okay, someone with new sexual partner, not so clean sexual partner, that's suspicious for acute hepatitis B. An Asian with multiple family members with hepatitis B, that's more likely exacerbation of chronic hepatitis B. So, it's really looking at all these sort of detective hints that help you. I think the reason it is a challenge for us is exactly that. Just last week, I had a gentleman who was 80 years old, looks like a flare, really high ALT, antibody positive, antigen negative. But if we call it an acute, then no other risk factors, you know, 80-year-old, no other risk factors for acute B. But if we call it an acute B, then it creates a lot of work. We're looking for healthcare associated infections. He had a dentist visit, you go to the dentist's office. So it's, even with epidemiologists doing the investigation, it's always not easy to sort out. Well, I mean, we can't solve every single problem on Earth. Next question. Sorry, Dr. Locke again, you know. Currently, do you think there's a role for genotype testing, hep B genotype testing or pre-corp mutant testing, especially in patients like in the gray zone or in HCC surveillance, or in sort of altering HCC surveillance recommendations? Routinely, I would say no, because it's not important to make a decision as to whether you start treatment or not treatment or cancer surveillance or not. But there are some instances when it could be helpful. And we certainly know that genotype C is associated with a high risk of HCC. Basal core promoter mutant is associated with a high rate of HCC as well. But there are other factors that are just as important, if not more important, male, older age, presence of cirrhosis, those are just as important. So the single test is not going to sway your decision too much. I find that the HPV genotype testing is perhaps not most valuable. If you happen to have a Caucasian patient that you're planning to treat and who is amenable to consider interferon therapy, because I've seen it several times now, they have genotype A, oh my god, they're going to clear S. I've seen like a lot of times that, hey, I mean, this gives me good reason to try to convince the patient to consider interferon. Because S energy loss is a big deal, right? Hello. It's Dr. Samonakis from Greece. I apologize for asking Dr. Lok again. Do I get paid twice? Sorry. Actually, it's $0 times twice, so it's still equal to zero. So I'm coming back to the issue of patients with positive family history for HCC. And as you know, we have many patients, E antigen negative. And consider that you have patients that they do not fulfill the criteria for treating them according to the guidelines. I mean, an HPV DNA less than 2,000 international units, completely normal liver biochemistry, ALT less than 20, and fibrosis score F1 or F2. So would you still recommend, if the patient has a family history of HCC, maybe the mother or father at the 70s had an HCC, should we implement immediately the antiviral treatment or should we follow up and at a certain time point, maybe an age or maybe a change in the status of the patient, we should commence patient on antivirals? This is a question that comes up very often. We know that if someone has a family history of HCC, they will have a higher risk of getting HCC. The question is always, do you then put them on antiviral treatment? Do you start HCC surveillance, even if they're 25 years old? I don't know the answer to that question because in Greece, as well as in many Asian countries, if you look at a Chinese family, they have a family history of HCC, but actually their mothers, it's HBS antigen positive, maternal uncle is hepatitis B positive, maternal aunt is hepatitis B positive, three cousins are hepatitis B positive, so one of them have HCC. Does that mean that their risk is very high compared to other people who are HBS antigen positive? I don't know. And if there's one single family member diagnosed with HCC at the age of 70, is that risk the same as a brother who was diagnosed with HCC at the age of 30? We don't know. I would love some of these young people to really dig deep and generate those data because family history is dependent on how many family members, it's dependent on how close, it's dependent on what age they were diagnosed, and it's also dependent on how many B positive family members you have in your extended family. So it's difficult, but short answer is sometimes it's also dependent on how freaked out the patient is because sometimes they're so freaked out that they will not take no for an answer because they would want the treatment, they would want the HCC surveillance, but if they're not totally freaked out, then you can discuss with them. Generally speaking, I do lower the threshold. I might start doing cancer screening at the age of 30 instead of 40. I might use a slightly lower threshold, but I wouldn't say that if your DNA is only 50 and your liver enzyme is 15 that I would put all of them on treatment. We have time for one final question. Thank you. My name's Greta. I'm from the University of Minnesota. Everyone was wonderful this morning, but I also have a question for Dr. Locke. My question is regards to I'm seeing a lot of individuals who have been getting IV, IG infusions and were previously core positive, negative, and now are having these possibly transient core positive labs and just wondering how do you approach this, if they stop IV, IG, or if they continue to get it long-term? Read up our paper. This is actually a fairly common phenomenon. One of my colleagues in MD Anderson was telling me that the oncologists are freaked out because now the patient is core antibody positive. Do I need to think about prophylaxis antiviral? If you actually know that the patient was core antibody negative before the IV, IG, and now they're positive, this is a passive transfer. It's not that the patient get infected. It's a passive transfer of antibody in the IV, IG. We actually plot it out. You see that the decay is very quick after the first four weeks. By 12 weeks, majority of these patients, they would become core antibody negative. The key is really having screened the patient beforehand because if you know that they were negative before and they recently received IV, IG, and they're now positive, it's not because they're infected. It's not because they have virus in the liver, and then you're reassured. The problem is many of these patients were not screened, and now they test positive and you have no idea. Well, if it's just within a few weeks of IV, IG, chances are this is passive transfer, and you might sort of monitor the patient. Okay. Thank you. Thank you. Well, I just want to thank our speakers for staying for the panel discussion and being generous with their time, and all of our speakers who participated in this course. Thank you for attending, and that'll conclude today's course. Enjoy the rest of your meeting.

Hepatitis B

prevalence

management

tests

treatment

reactivation

genotype testing