#440 Hepatitis B with Dr. Arthur Kim

Hey listeners, it's 2024 and we are so excited for everything ahead this year. If you haven't done so already, make sure to check out our Patreon at patreon.com slash curbsiders where you can get access to bonus episodes. We've already released eight. That's patreon.com slash curbsiders. Paul, what is the most dangerous insect? You're just jumping right in. I don't know, Matt. What is the most dangerous insect? The hepatitis B.

Are we 100% sure that bees are insects? All right, Paul, one more. Fresh thyme blackberries have been linked to a hepatitis A outbreak in three states. Paul, this is... Very bad news. That might be my favorite one that you've done.

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Welcome back to The Curbsiders. I'm Dr. Matthew Frank-Watto, here with my great friend and America's primary care physician, Dr. Paul Nelson-Williams. Hi, Paul. Hi, Matt. How are you? I'm flying high because you said you liked my pun. But then I questioned if bees are insects and I feel like an idiot. So we're going to have to record the intro again. I am an idiot. Yeah.

Well, we are talking about hepatitis B with a great guest, Dr. Arthur Kim. We'll tell you all about him in a second. But Paul, will you remind people, what is it that we do on curbsiders? Sure. Happy to. As always, Matt, we are the internal medicine podcast. We use expert interviews to bring you clinical pearls and practice changing knowledge. And I should mention that we are joined by a third co-host, someone that I often refer to as my future boss. We are joined by Malini Gandhi.

monnie how are you i'm good i'm good yeah paul she's she's getting ready to uh start residency and and you know maybe take a brief sabbatical which is bad news for us but she she does she has done many of our greatest hits over the past few years so and this certainly will join that uh as another great one so can you tell us about our great guest

Sure. We had a fantastic conversation today with our guest, Dr. Arthur Kim. Dr. Kim grew up on the West Coast, but has now lived three decades on the East Coast and is an academic infectious disease specialist at Massachusetts General Hospital in Boston. His main focus has been on viral hepatitis, especially in special populations, such as persons who use drugs, persons with HIV, and persons who are immunocompromised.

Today, we had a great conversation with him. He taught us a lot of wonderful pearls on hepatitis B screening and vaccination, as well as his approach to counseling and treatment considerations in patients with chronic hepatitis B. Without further ado, let's get to it. you

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Arthur, thank you so much for bearing with us through technical difficulties and, you know, finally getting to record this episode on hepatitis B. But before that... Audience wants to know a little bit about you. They've heard your bio, but they want to know a hobby or interest that you have outside of medicine. Okay, so the hobby that I've chosen is board games. I guess about...

20 years ago someone introduced me to this thing called settlers of katan and it just kind of took off from there uh growing up i played a lot of the classic ones like monopoly and all of that but um from that point on i was really hooked on these sort of modern board games and so that's probably the the main hobby that my wife and i enjoy with with several other couples and with our kids so

It's a nice escape from the sort of digital realm. That's good. I admire that. Did you watch the Parks and Recreation? There was the Ben... whatever his name was on that show. He made this like insanely complicated game that like no one wanted to play with him and then he became an accountant and all the accountants thought it was like the most exciting game ever. I just, yeah, I love that. I thought that was, I thought that was great.

Paul, you're a big board game guy, right? No, you need friends to play board games with. It's been a real barrier for me. I can collect them as a matter of interest, but I haven't had a chance to play too many of them. You've never invited me to play a board game. I consider myself a friend. Well, we can talk offline.

Arthur, I'm going to ask a different question, not board game related. We do like to ask about favored failures. That doesn't even have to be a failure in medicine or a medical mistake or anything like that. But is there just a failure in life that you learn something from or that you just you have affection for in retrospect? Yeah.

I was thinking about this and I was thinking back to middle school, you know, the most awkward time in life. And it's actually softball related. So if you'll bear with the brief story, in middle school, there was a softball game where the... Seniors, I guess, were facing the faculty. And it was like a really small private school, so it's not like there's a team or anything. So we'd cobble together a team, co-ed.

And I have to say, in retrospect, this must have been a chance for teachers to just beat down on the kids because they'd usually win 14 to 3 or something. But somehow, I was chosen as captain. followed baseball really closely back then. And this one year, we kept it really close. And then we're...

It's like our last at bat. We're down by three. We have the bases loaded, you know, the classic situation. And I have my best batter up and he's already like hit two doubles. And I'm like, this is great. And he comes over to me and says, hey.

I think we should do a surprise bunt. And if anyone knows anything about baseball, that is like absolutely the wrong thing to do. But I was like, sure, great idea. And, you know, I'll... take that because i was the manager and so that was all my fault and so everything goes south predictably after that so um you know i think about that now while i'm very much into the idea of leadership where you empower those you know who are you're leading um sometimes

you just have to say, wow, that's a terrible idea. We just don't do that. All right. Before we get onto the case, Malini, anything else you wanted to ask?

Yeah, we like to ask also about a piece of feedback either that you've received during training that stuck with you or that you like to give to your trainees. Well... I like to reflect back on a statement that I can't remember who made it, but just it was stated so succinctly and eloquently, but it was just that it's a privilege to be in the position that we're in.

We are often coming alongside patients at a time in their lives where perhaps there's a crisis or just, you know, we're there to promote health. And every intersection is a chance to communicate and as well as connect. And so I think trying to be mindful of that every day, it's kind of hard, but we're there with patients in their sickness and in their health.

That's just like a sacred bond that we have. So just try to keep that mindful every day. Yeah, it's definitely easy to lose sight of it when you're in the middle of like a grind of, you know. a week of lots of clinic or inpatient service, whatever you're doing. And yeah, so it's good to reset like that. Well...

This is a topic that I know near and dear to your heart, which is why we have you on. And we always start with a case from Cash Slack. So we'll let Malini do the honors of starting us off here. Sure. So we have a patient, Mr. L. He is a 54-year-old man. There's no prior history of liver disease. And he presents for an initial primary care visit with you.

He had immigrated to the U.S. from China at the age of six, and he tells you that he can't remember if he ever received a vaccination against hepatitis B.

So we wanted to start out just talking about screening for hepatitis B. And we know that the guidelines have actually from the CDC have recently changed on this. And so we'd love for you to talk a little bit about what that change was, what the rationale is, and in general, how you approach screening. Great. Yeah, so in 2023, there was a change in the CDC guidelines now stating that all adults should be screened for hepatitis B at least once in their lifetime.

So prior to that, there was risk factor-based screening. So selective screening based on your interview, who the patient is, where they come from. And so this gentleman who emigrated from China... probably would have prompted screening if you think about his origins and the high prevalence over 8% of potentially having chronic hepatitis B. And so now it'd be...

pretty much anyone in the office, for which you haven't screened before, to take it more to everyone, just like we did with hepatitis C three years ago. So, I mean, this decision... It wasn't taken lightly. This is a CDC-level recommendation after sort of an expert work group and lots of systematic reviews and peer reviews. And, you know, once they looked at this, they said, on balance, we feel...

like we should screen everyone, at least all adults. So the idea behind screening, is it both to find people who have... been infected and can now receive treatment because I know there's no cure for hepatitis B yet, or is it more to... Just try to get people vaccinated, you know, recognize who has not been vaccinated, who doesn't have protective antibodies and get them vaccinated. Is it both those things or did one lead this more than the other?

I'd say it's all of the above. I think hepatitis B as a whole is a great candidate for screening. And even amongst those who don't have chronic hepatitis B, they are often candidates for vaccination and prevention. I guess when you think about any sort of screening test, if there's an asymptomatic period before consequences, that's a great criterion, and it's definitely met here as this.

infection can take decades before disease. And this is a transmissible infection, and so you can counsel about further prevention. And then it is a major cause of cirrhosis as well as liver cancer. And then finally, you have great treatments. So there are antiviral treatments. There's no cure yet. We could talk about that later, that they're working on a cure.

But at this point, we can do something about it to mitigate those downstream consequences. And so given that balance, as well as the fact that they did analyses showing that it's cost effective to screen everybody, even though the yield will be lower. that this recommendation went forward. And I think it's being pushed out right now in sort of electronic health records. And so some of you guys in primary care may be taken by surprise by this unless you've been prepared for it.

Yeah, Paul, for me, this showed up last month. How about you? No, I was going to say, I remember being annoyed by this change, if only because when precepting residents, I always had that in my back pocket in terms of vaccinations for patients with type 2 diabetes.

Like that was one, like I could always pull out and ask questions about and sort of trick the residents and feel smug. And now, now it's everybody. So I don't, I don't have that anymore, but it's, but yes, it's also been showing up as like a best practice advisor. You're like this kind of alert that now pops up, whether though we were talking off air, it does not. often accurately capture who has been vaccinated, who has not. So that's been a challenge.

Yeah, Arthur, can I ask where this has been tripping me up a little bit, how to counsel patients? You know, some patients I say, oh yeah, I'm going to be sending hep B screening. And they're like, yeah, sure. And other patients would be like... haven't I been vaccinated for that already? So like for people who have been vaccinated or people who are uncertain if they've been vaccinated, how should we counsel them? Because the screening test, it checks surface antibody and surface antigen.

And I think it checks core antibody as well. Yeah, let's call it the triple screen. Let's just take a step back. Hepatitis B, let's just say it's complicated, right? There's all these different stages. There's like different tests. There's the core, the E antigen, the surface antigen.

So I think we'll spend some time on that later. But it's not like hepatitis C where you send an antibody and then you confirm. That's much more straightforward. Here you've got a variety of tests. You have a surface antigen test that looks for chronic infection. You have surface antibody, which generally doesn't appear at the same time as the antigen. They're mutually exclusive for the most part. And that antibody is indicative of immunity, which can be either natural.

from infection or from vaccination and then there's the core antibody which i think deserves a lot of attention since i think up until this point that hasn't been a universal screen by any stretch so getting back to your example That gets right to the heart of this case. This gentleman emigrated to the US from China. If he went to school here, he was...

probably pretty likely to be vaccinated at some point, you know, when the vaccines came out and then was universally recommended for adolescents. And then schools were very interested in having that in their immunization requirements. So, but if he had chronic hepatitis B, then giving vaccination doesn't do anything, right? It won't cure the infection. It's not an immunotherapy. The virus will just laugh at it. So this guy's a kind of a...

perfect example of someone who not only comes from a country and could have been infected either through his mom or even through sort of injections that occurred, you know, 53 years ago when he was an infant. And if you identify it now, you can potentially really change sort of the course of his life. If he developed liver cancer shortly thereafter, you know, that would be kind of a big miss.

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So basically, for my patients who are unsure if they've been vaccinated, I mean, we can just order this test regardless of whether or not someone thinks they've been vaccinated or exposed to Hep B. We can screen them just to see what those three tests show and kind of go from there. Yes, and it will produce a lot of different scenarios, but the basic answer to your question is yes. Even if you have documentation of vaccination, you might justify screening.

Let's just take myself as an example. So I was born in Los Angeles and received vaccination as an adolescent. My parents are from South Korea, a high-prevalence country, and my mom could have been infected and given birth before screening. And I could be harboring hepatitis B, and I have colleagues who are in that position.

Born here, you know, in the old guidelines, you'd have to remember that. Oh, okay, so do you ask about every patient's country of origin of their parents? Usually not. So that's kind of one way you would miss it for me, and I would... potentially go around thinking i was vaccinated and fine and so i would be a candidate for screening even with good documentation of vaccination and so given how complicated it is and given how complicated remembering all the risk factors are

I could ask you guys, what do you think? Is it simpler to just say, okay, let's just get it done once for everybody, and then we'll deal with the fallout of the different scenarios afterwards? Or would you rather go back to risk factor base where you've got to ask all those? questions about sex about you know blood exposures and where you're from and where your parents are from well it's a fun history to take paul but what do you think yeah no i mean i

Obviously, I think the universal screening is probably easier and then sort of sorting things out after the fact. Though I would ask, Arthur, it's easy for like these health maintenance items to kind of fall through the wayside or sort of be disregarded.

Can you just talk us through some like can't miss scenarios where we really need to know hepatitis B immunity status? Like, so we'll say up front, we should be screening everybody, but it's easy to kind of let things slide. So who are the people that we really can't miss and should be screened very aggressively?

Yeah, so there is still a list of people who you still may screen after your test again once they've been screened once, and these are persons with ongoing risk factors. or with more risk than average. And so let's take the risk factors. So let's say there's someone who doesn't have adequate immunity and they're out there with multiple sexual partners. And this is a highly preventable disease.

screen this gentleman or woman and you determine their status, you can then decide to vaccinate them since they're at risk. Or if they have it, then you can counsel them about further transmission. And so really that's kind of a dual purpose. And let's take a scenario where there could be what happens with hepatitis B, which is reactivation. And whether you're in the chronic state or even if you're just core antibody positive, there are situations...

We take away the immune system and boom, hepatitis B goes off and it reactivates and it sends some people to liver failure.

And so for patients who are undergoing cancer chemotherapies, for persons undergoing immunosuppression, there are consequences that can happen short-term. And that includes... certain like monoclonal antibody therapies that suppress b cells and things like that too right yeah yeah when you go through the list of different immune modulators that can reactivate the b cell depleting therapies

The most commonly known one is rituximab, and it's increasingly used for a variety of conditions, not only cancer, but a lot of autoimmune diseases. what we consider kind of the highest risk, JAK-STAT inhibitors. I mean, in rheumatology and autoimmune conditions, you know, there's a whole host of biologics, and many of them include a warning about hepatitis B. And then, I don't know if you guys saw this paper, but recently JAMA put out this letter stating that at any given time...

About 6% of the population might have an immunocompromising condition. And so that's just a point prevalence. I mean, over a lifetime, you know, there can be a higher risk that at some point they get immunosuppressed. Okay, so yeah, this is a high-yield topic, I would say, Paul.

Okay, so I've definitely seen that come up too. Sometimes in the hospital, we're rushing to get these done before we start immunosuppressive therapy on somebody. And that was one of the first times I had heard of this, to be frank. Because that doesn't come up too, too often in the outpatient setting because usually the hematologist is seeing them in their office and handling the testing. But we should be aware of it as well.

Okay, so Malini, do you want to go through some of these scenarios, like how we're going to be interpreting some of the testing? Sure, yes. So I know you started to get at this earlier, but... when these tests come back. And we have this triple test for hepatitis B surface antigen, core antibody, and surface antibody.

how are we interpreting the various permutations of negative and positive for all of these? So I'd love if you'd be able to walk through the common scenarios for each of those. Sure. Well... One thing is to have that table handy. So whatever reference you have, there's, I'm sure, a handy-dandy table, including at the CDC screening recommendation website. So let's go through these markers.

you know, the core antibody is kind of what's developed first, and that indicates exposure. So you can think about that kind of like the hepatitis C antibody, which is only about exposure. And so it doesn't tell you anything about whether the disease is active or not. And so let's put that one aside and then talk about surface antigen. And antigen is...

really the best screening test to look for chronic active infection, and it can also pick up acute infection. And then the surface antibody is what we use as a marker of immunity. Let's take someone who's core positive, exposed, and then has surface antibody immunity. So we would consider that patient recovered from hepatitis B.

And then if you're core positive, if you have the surface antigen positive, active disease, then that's either chronic or less likely acute. So then there's a situation where there's no core. positivity and so at that point um they shouldn't have a surface antigen and then they could be antibody positive or not so i mean we just went through a few permutations it's kind of hard without that chart but um So that will lead you to several potential actionable items if they're surface antigen.

positive, I guess it's referral is kind of the thoughts, although we can talk about what roles primary care could play. And then if they're surface antibody positive, you're kind of done. for the most part. And then if they're negative, then you vaccinate. And so we didn't quite mention it, but in 2022, CDC also recommended an almost universal adult vaccination recommendation. So for...

sort of 19 to 59, they recommend vaccination for those who are non-immune. And so having that test will help define that population much better for you. So that's the rationale behind the triple screen. I do acknowledge. It's complicated. It's not just sending the antibody for hep C and getting the RNA afterwards. This is like a whole matrix of different scenarios.

For our trainees out there, the boards love this, by the way. So yeah, the table's nice, but they love testing on the permutations of the triple screening. I don't know why. I was going to mention that, so just to remind the audience, you said the hep B surface antigen and the surface antibody usually don't appear together because they're usually exclusive. Any common false positives that we need to be aware of?

just, you know, common pitfalls to these tests? There are pitfalls, absolutely. So firstly, the core antibody. that can be positive when people are giving sort of blood products or IVIG in particular. And what's ironic about that is, you know, persons who are getting IVIG for whatever condition, immune modulating condition, they kind of eventually end up on a biologic such as rituximab and then you're kind of stuck. You can't go back in time and test.

them because they're getting all this core antibody that's coming through their IVIG. So that's one regarding the core antibody that can get us in trouble a bit. And so I do think that if all adults receive that screen and have a core antibody at baseline when they're not on that stuff, that's going to help reduce the number of questions to us in ID and hepatology. The surface antigen, there's a pretty important one, which is that You may be vaccinating and testing on the same day.

Because you might say, well, there's someone in front of me. They're at high risk. They've reported to me a risk factor. Let's just take injection drug use. And I want to not only test them, but I also want to vaccinate. because they're in front of me and I don't know if they're going to come back and they're on the list for vaccination. And so what you want to do is do it in the correct order. You want to test first.

and then vaccinate. If you vaccinate first, there's actually surface antigen in that, and it can leak into the bloodstream, and the test is so sensitive that it can pick it up. And it can pick it up up to days, or in some cases, weeks afterwards. You don't want to deal with that type of false positive. That's one of the rougher ones to deal with because you're telling the patient, oh, you could have surface antigen, you could have chronic hep B, and then you're trying to sort all this out later.

Oh my God. Yeah, I didn't think of that. So it's just as an immune stimulant, there's some inert surface antigen in the vaccine, which could then cause... Because the false positive test, and you said even weeks after the vaccine, potentially. Yeah, usually, I think the longest reported... the CDC mentioned was 18 days. So I would say usually just days afterwards. Yeah. So in your clinic, you draw the blood and then give the vaccine in that?

In that order, if you're doing it at the same time. So that's one tip as you're implementing this, because I think you'll be in that situation at varying points. And at least once in your career, someone may do it in the opposite order, and you'll say, oh, okay, I figured this out. Okay.

So speaking of vaccination, so let's start to talk a little bit about this patient. Again, we don't have our testing back yet. He wants to know if he should be vaccinated. This is a guy that... was born in China and came here, and we don't know his vaccination status. Yeah, I mean, I think it would be reasonable to kind of await the results, unless you think...

that between now and the next visit that they're going to be out there doing something that places them at risk. So I think that that case scenario is probably rarer. And then you could kind of regroup after your test in this instance. But given that he is in an age group, being from China from 50 years ago, that is pretty high prevalence. I'd say overall it'd be reasonable to wait for this gentleman.

But if you were working with a high-risk population, like in a... I don't know, buprenorphine clinic or something like that, and you thought somebody was, you know, high risk of you could just vaccinate before the testing came back in that kind of scenario where it was a higher risk that they'd be exposed to infected blood products.

Yeah, CDC has been saying that for quite a while, that don't hesitate to vaccinate. You know, one reason why a lot of folks were not vaccinating for hepatitis B, it's like, well... We don't know if this person's going to come back and be right on schedule for the three dose series. So let's just wait until a period when they can come back at exactly week.

four or eight after their first one, and then six months later. But, you know, that's not quite how vaccines work. I mean, if you give three doses spaced apart a certain amount, you have a very reasonable chance of achieving immunity. That's not how it's studied. This is off-label, obviously.

But the idea is for patients with increased risk that you would definitely take the opportunity to vaccinate. And if they intersect enough times with the healthcare system, hopefully they will achieve immunity.

Malini, what else do we want to know about vaccines? Yeah, I think one thing that has come up is... kind of different varieties of hepatitis B vaccines. I would love for you to talk a little bit about what vaccines are available for us, what you'd recommend in different settings, and what populations you might recommend giving CPG-adjuvated vaccines, which I know is...

is also available. Sure. Well, I think on this podcast are all healthcare workers. So we all got the traditional vaccine, most likely at some point, I think. probably in childhood for the youngest ones, perhaps right at infancy. And we got the traditional three-dose vaccine that we're all kind of used to. And then what's also available is a combination with hepatitis A vaccine.

That's more pricey, but gets you to vaccinate populations for both at the same time. And there are actually two newer ones that... your listenership may want to hear about. One is called Prehebrio. Have you guys heard of this one? No? I have not. Yeah, so this was recently approved, and it's adjuvated kind of the same way as the old ones, but it includes three different antigens related to surface antigens, so it's kind of got more.

And it achieves seropositivity at about the same amount. The titers are actually higher when you look at the actual number of the antibody. And so while it hasn't been out long enough for us to really know this, it may sort of last longer. But it is newer and therefore more pricey than the traditional vaccine. And then we have the CPG-adjuvanted vaccine. And so this one's been out, I think, since 2017. Approved for adults. It uses the TLR9 as its sort of stimulant through its CPG.

And so that adjuvant gets you more bang for the buck and you are more likely to respond properly to the vaccine. And so recently there was a randomized trial. I think you guys like in your evidence-based reviews, you love the randomized trial. And so for persons with HIV just last month, there was a very nice...

randomized trial showing that whether you get two doses of this new vaccine or three doses of the vaccine, it's better than traditional vaccine if you need a good immune response. As most people living with HIV, you kind of want a good response. That kind of suggests, and I think there's data in a lot of settings where we're getting more comfortable using this vaccine. Is there a big cost difference between the CPG vaccine and the traditional one right now? There is a cost difference.

But you can also do the two doses, and so that mitigates some of the cost per dose. So I'd say you can stick with traditional vaccine for the base case scenario, but... I think for scenarios where you really want that antibody, for instance, for a patient who's a transplant candidate, and they have end-stage, let's say, renal disease, we know those folks don't respond well to traditional vaccine at all. And so this is a group that I don't think that's on the label, by the way.

where we started to use it because we want people to have full immunity. We know vaccines will work better. prior to transplant than after transplant. So those are kind of scenarios where we're beginning to use it. And this trial for HIV, actually, for that population who also don't respond well to traditional vaccine.

For you guys, the usual case scenario may be someone who didn't respond to vaccine and they're a non-responder. And so you will face that scenario if you're checking these triple tests in people who are previously vaccinated. We could walk through what you do there if that's helpful. It definitely would be. Yeah, yeah. So...

What happens, and this is where it gets a little confusing, is that when you get hepatitis B immunity, you kind of shoot up your titer against the surface antigen. The surface antibodies can be quite high and then over... The next years to decades, well, guess what? Without any antigen stimulation, it just kind of goes down over time. And so it can be there. You can have B cells ready to make that antibody. And so when you face the situation where somebody...

is seemingly a non-responder to vaccine, you could try to revive that. You can give maybe one dose of vaccine and check four weeks later. And if they get their surface antibody back, you're pretty happy. If they don't, then you just proceed with another revaccination series. And so I think the usual algorithms now would use traditional vaccine for that second round.

I think at this point, if you have it available to you, many practices have actually moved to this two-dose CPG vaccine because it gets you there faster and it's only two doses rather than three doses. So there's...

some subtlety here, but I think some practices could say, well, yeah, I can really see where that would help because you don't have to bring them back for a third visit. There's costs associated with that. And it kind of cancels out any cost of the vaccine. And these vaccines aren't like... budget busters by any stretch.

Yeah, I know. I know sometimes practices worry about like you have to pay for the vaccines up front and you're not exactly sure how many you're going to give. So I guess there's some of that math that's involved. But so the vaccines to recap for the audience, we have the traditional three dose. We have the combination hep A, hep B.

which you said that one can be pricey, but it's kind of convenient. And you said there's one called Prehebrio. Is that what you're saying? Yeah, Prehebrio, I think. Prehebrio, and then the CPG adjuvanted. adjuvanted one was the most recent one we were talking about. And particularly if someone hasn't responded to the traditional the first time, that might be a good way to go if it's available to you.

Absolutely. And I think healthcare workers who are at risk for needle stick injuries, who have not responded to traditional vaccine, that's another group that I think occupational health is pretty interested in using the novel vaccine. Yeah. Okay. What if it's somebody that for whatever reason, we know at one time they had a positive titer, but it gets checked again, and then now the titer is gone.

Is that somebody still, you can still boost them? I thought I was reading, I thought the vaccine immunity might even last up to 30 years, something like that, in one of the articles I was reading. For someone that was vaccinated like age 20 and we check and they're 45 or something now. And they told us, oh, yeah, I'm pretty sure I responded. I was in the military and they checked.

I didn't need to get revaccinated, but now they're 55 and they got it checked. In that scenario, would you revaccinate? That's a great question. I mean, overall, as you can tell, I'm pretty pro-vaccine, infectious disease guy, right? And I think... You could interview this theoretical patient and try to figure out risk factors. And if you ping on any risk factor, you'd be like, okay, yeah, yeah, let's go ahead. But...

You know, there's so many indications, even like travel. And so if you're a 50-something-year-old... person may travel a lot in their 60s and in their retirement, and maybe in a situation where they're exposed via healthcare in some country somewhere. So I would basically have a very low threshold. And then people may not actually report to you their risk. And so...

You know, I've had persons who are perhaps in a monogamous relationship, but may not disclose to you sort of some extracurriculars and say, you know what, doc, I kind of want the hepatitis B vaccine. And so... You'll see in the guidance, the CDC guidance on this, to just give it and also to screen for it because they don't want... patients to have to disclose risk to trigger these things because some of these do have some stigma or may be underreported.

Can you just comment briefly on the safety of this vaccine or how do you counsel patients about like potential side effects? I mean, is Guillain-Barre something that's been observed in this or any other? sort of more serious immune complications? I think for the CPG vaccine, what they've seen so far are largely more local site reactions. So I think that's the main thing to counsel about. I'm not aware of sort of increased risk of Guillain-Barre related to the novel vaccines.

With hepatitis B vaccine, if you go back in the literature, you'll find all sorts of things. But overall, I don't think there's been an incredibly consistent signal. And I think you guys... kind of consider it one of the safer vaccines out of all the ones you give. And so the new one, it's the same antigen, just with this TLR9 stuff. And so far, not really aware of sort of autoimmune phenomenon.

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Malini, should we go to the next part of the case here? Sure. It sounds great. So let's say we decide to screen our patient and our hepatitis B serologies come back positive for hepatitis B surface antigen, as well as core antibody and negative for surface antibody. So he asks us, Doc, what does this mean? So how would you explain this to the patient? And how would you go about describing to him what the natural history of hepatitis B infection is?

acute infection to chronic infection, the various stages of chronic infection. Yeah, so I do think it is a good idea to take a quick step back and just think to yourself whether it could be acute. And so... Generally, you'll get an ALT, and if you see the ALT much more markedly elevated than expected, that could be acute.

But it could also represent any of the immune active phases. And the IgM is actually positive in all those phases. So let's put the acute aside since that's not very usual. But you may... want to know about risk factors a few weeks before. So for acute hepatitis B, the incubation time is generally several weeks. And that's true of actually all the viral hepatitis. So my colleague in Brazil... who sees a lot of acute hepatitis B, she sees

kind of a spike in cases a few weeks after Carnival, where under-vaccinated folks are having a bit of fun there. And pretty reliably every year, there's kind of a rash of some acute cases that present. And so... For chronic hepatitis B, which is the probable scenario here, it's kind of a mixed message, I have to say, because...

Many patients are completely fine with hepatitis B and may die with hepatitis B and not of it. And yet, despite that reassurance, there's a fairly reasonable risk of liver cancer. as well as liver disease. And unfortunately for hepatitis B, it's a DNA virus. It kind of gets into your DNA and kind of can be carcinogenic. And it can cause hepatocellular carcinoma before cirrhosis. Most of the liver diseases don't do that, but hepatitis B does. And so...

When I say mixed message, I mean like this is a potentially serious condition, but I don't want to overly alarm you. Knowledge is really the first step that we know about it. And now with proper monitoring. and potentially treatment, we can really mitigate your risk. And the whole goal is so that they, again, they die with the hepatitis B and not because of the hepatitis B.

So you mentioned some of the phases there. So this could be acute hep B, which we put aside for the time being. You said it could be chronic hep B, and you talked about the ALT. If that's high, that could mean it's one of the active phases. Can you just like kind of briefly go over the phases of the chronic disease? I found these a little bit confusing. Yeah, the board's question, right? So what they call...

The first phase of chronic hep B, which is immune-tolerant phase. So the ALTs are generally flat. So you're tolerating this infection. The immune system... is kind of not sending its lymphocytes into your liver to cause inflammation. And so this tolerant phase can last for generally decades if you're infected when you're... perinatally or as an infant. And then somewhere around the second or more likely third or fourth decade of life, they pass through an immune active phase.

The immune system decides, hey, let's do something about this virus. I can't tell you why this happens, but then... With that immune active phase, you'll see ALTs rise, and the hopeful outcome is that they pass through their e-antigen seroconversion, their e-antigen disappears, and then their e-antibody develops. And then at that point, the viral load or the DNA test, which you'll be following at that point, should then go down.

The patient will be less infectious, just associate that E antigen with being more infectious and more virus. And then some can go to sort of a very inactive state with a very low hepatitis B DNA. And again, the ALT normalizes. Finally, then it wakes up again. And at some point, and this can happen with immune suppression, but it can also just happen with aging. They activate again and the...

in the E antigen negative immune active phase. And that's when we want to treat. Basically, we want to treat when the ALTs are up. And that's where a lot of the treatment guidance goes. Although... And internationally, DNA is not always available, and so there's been a movement to simplify things and just put people on therapy. But for the U.S. setting, we'll be using the viral load or hepatitis B DNA.

Okay, so the tolerant phase, if someone's infected at birth, like presumably our guy here was, he may have been in the immune-tolerant phase for decades, and then... Eventually, it becomes immune active where ALT goes up, the immune system's active against the virus. And then at that point, usually the E antigen is still positive, right? They're still infectious.

If they convert to the E antibody, and then everything can kind of cool off, the viral load can drop, the ALT can go back down. But then again, even with the E antigen negative, they can get into another active phase. and the ALT can go back up. And you said basically in either of those active phases, whether the E antigen is positive or negative, those would be potential times we would treat. Am I summarizing okay? I think that's about right.

It's potentially rarely an urgency to treat unless they already have cirrhosis and you really don't want them to activate. And so sometimes with just a bump in ALT, we'll kind of give them a little bit of time just practically before we start treatment. Overall, to simplify treatment, yes, that's exactly what you said. When things are active is when you want to shut things down so that there's not disease progression within the liver.

um because that's where you see the sort of fibrosis the immune response is pretty responsible for a lot of the damage that happens there and and so yeah it's complicated as we said at the beginning this this virus is

less binary, I guess, in their virologic outcome than, say, HIV or hep C. Paul, you haven't asked anything in a while. What are your thoughts on this? Yeah, it's kind of bewildering. I mean, it's very helpful. I mean, I'm much clearer now. I would say this is a great case because I feel like this is something that comes up and say these lab results come back. I think it's helpful to know the stages and sort of delineate them.

This person is almost certainly getting referred to one of my colleagues, either hepatology or infectious disease or possibly both. So I guess the question I might ask is what initial lab tests might we get that would sort of help? move things along and make sure their care is sort of facilitated so they're not waiting for more answers once they get to their specialist visit. So what are the initial things that we should check just to kind of get them on their way to ongoing evaluation?

Yeah, so I think there's a great primary care guide, by the way, at a site at the University of Washington that has a great table for this. And so perhaps we can inform your readers of that and point them there. What that includes are several labs. Firstly, sort of a comp metabolic panel is super useful. You want the ALT. You want the bilirubin.

And then you kind of want kidney function because that affects a little bit treatment. And there actually are some renal manifestations of hepatitis B as well. But that usually comes with any comp metabolic panel. CBC would diff. Any sort of cytopenias, especially in someone who's already 54 or older, if you see that lowish platelet count, that starts to get you a little worried.

That's like the quick screen for advanced liver disease is the platelet count. But then you can combine that with... some of the other labs from your comp metabolic panel um and and calculate what's called like an apri score of fib4 i don't know if you have like dot phrases or or in your medical record And if not, there's also calculators at the University of Washington website. And then you already have an idea of whether they might be at risk for advanced liver disease.

I'd say most of us would recommend an ultrasound because, as mentioned, cancer could be there, and an ultrasound is a good screening test for that. And generally, we do screen with an ultrasound, with or without. an alpha fetal protein. And then for an older person who might have advanced liver disease, I might also send a PT-INR, you know, just there. I wouldn't necessarily send that in a younger individual.

And then co-infections. So anyone with a risk factor for hep B and their disease course would be modulated by it, by these infections. So HIV and hep C, which are also universal, so you've probably already screened for them. And then... Delta. So as a reminder, hepatitis D or delta, this is a virus that's defective and can only exist when hepatitis B is active. So you should really not look for it unless you know there's hep B around.

And so I think most of us would recommend sending that along. But you could wait for your specialist as well if you're uncomfortable with that.

That kind of goes over most of the list that I think we'd recommend that you get started with while they're awaiting their specialist appointment, hopefully without too much weight. And was the E antigen on that list? yeah it would be and for a 50 something year old gentleman i mean it's pretty likely that he's already e antigen negative just you know just by percentages and probabilities but yes yeah if you send that that will that will help

help out your specialist. Okay. I think we can handle that testing. Paul, what about you? Yeah? Yeah, I feel good about that. Okay. So this patient, let's say he's worried now about... kids and partners and pets whatever how would you counsel him like what does this mean for him about his participation in let's say he plays pickup soccer on the weekends or something like that can he participate in those things and

sharing toothbrushes and things like that. Talk us through it. All right. Well, I've seen a lot of... pick up soccer, and that can vary in its sort of brutality, I'd say. There's some weekend warriors, I think, who take it pretty seriously. But basically, we don't worry too much about casual contact, unless there's like an open wound. We definitely don't want to convey to patients that they should withdraw from various activities like that.

We definitely had people either counsel that way or they read it on the internet somewhere, you know, and they just like isolate themselves. They get scared to even hug their children. And that's just really negative and clearly not a way hepatitis B is transmitted. That being said, there is household transmission that's possible. So one should clean up any visible blood cuts, surfaces with bleach. One shouldn't share razors or toothbrushes. I think...

That's pretty common sense advice, but I like to remind people of that. And then it's, you know, the sexual partner, I think, does need to be tested. That's someone who you would definitely want to vaccinate and be sure they have a surface antibody if they're not already infected. And you can prevent hepatitis B with barrier precautions as well. And for persons with injection risk factors, you know, harm reduction is key too.

Let's see, what else do people need to know? Oh, breastfeeding. So breastfeeding does not transmit either hepatitis B or hepatitis C, but I've had patients in my office who were told that by providers. And so, you know, these are some... some misconceptions to clear up okay no toothbrushes that yeah that's it's weird how these things work like you'd think breastfeeding would be more of a risk right because it's a fluid you know but toothbrushing

I guess there's little micro abrasions from tooth brushing. Yeah, some people bleed, you know, if they're not doing it regularly. And so I think that's the rationale. Just seems hygienic anyway.

I feel like this comes out a lot, and I can't imagine a circumstance where there's going to be a lot of people are sharing, but that's just lack of imagination on my part. There was some, I think it was How I Met Your Mother. There was one episode where I just thought it was a great joke that all three people living in an apartment.

In a really clever way, they revealed that they were all using the same toothbrush because they all thought it was their toothbrush. And it was like so gross, but it was so funny. Oh, wow. Paul, you've already admitted you're a mouthwash enthusiast on a previous episode. Well, yeah, that will also happen. Oral hygiene, very key for our health.

What about sharing bites of food or sips of a drink? You know, that's also not recommended for people with hepatitis B. No, I don't counsel patients in that manner. I know there are some who are paranoid about it. those kind of things. But, you know, if you think about kind of shared utensils and whatnot, particularly in places like Asia, where there's a lot of family sharing of family-style meals, if that spread hepatitis B, I mean, everyone would get it.

Okay. All right. I think I'm done with my questions there, Paul. I don't know if you have any to add on. It felt pretty comprehensive, you know, whatever the toothbrush stuff. Okay. Malini, anything else before we move on to the next part? Yeah, I think you talked a little bit when you mentioned isolation, some of the psychosocial factors, and would love you to talk a little bit more about that, how stigma plays into this. Yeah, so, you know, there are met patients.

who have differing reactions, I'd say, to their diagnosis. And some really do carry a lot of stigma with it. And some of that is... generated by shame you know there is even if they were infected through some vaccine when they were one years old somehow they still feel like it's their fault or something and they feel like they're carrying something and so

I do like to explore that a little bit because that can impact their lives and try to talk to them about it. And hopefully through... counseling and whatnot can mitigate that to a certain extent but i've had some severe cases where i referred to like cognitive behavioral therapy to try to you know move on because i think if you're connected to care and you get the monitoring

that comes with this diagnosis. I mean, you can really mitigate all these risks if you think about it. You can vaccinate your partner so you can feel comfortable, you know, making babies with them. So, you know, there's... Each of these things we can mitigate. And so I do like to explore that just in case that's also a factor, since for some patients, that's the most impactful element of this disease.

Arthur, I do want to ask, so if you have a patient like this where you suspect chronic hepatitis B, we talked about... prevention of transmission, how do you counsel patients in terms of sort of liver preservation, which I guess is maybe a dumb way to say that, but like, is everyone with this diagnosis immediately getting a hepatitis A vaccine? How do you counsel about alcohol use, that kind of stuff? How do you talk to patients about sort of minimizing the damage it does?

I love that term, liver preservation. They use it in actually the transplant setting when they're... transporting organs. But yeah, so we definitely want to counsel about prevention of liver disease. And so number one, I guess, would be alcohol. And I'd say most U.S.

Practices are all about saying, well, you know, especially if you have advanced liver disease or you're older, you know, maybe you should cut that out. So that's one thing. Then the other major lifestyle factor are sort of diet and weight gain.

because we see a lot of overlap with that whole fatty liver, you know, renamed now steatotic liver disease. So we counsel about excess weight gain and if they are overweight or obese to... think about lifestyle changes when people ask about diet i usually say a heart healthy diet is a liver healthy diet and then people may ask about marijuana

There was a study way back when that suggested that persons who took marijuana would have more liver disease. But I think that's been more or less debunked in some observational cohorts that we're not really seeing that effect. And so that's probably neutral. I emphasize that it's neutral, that they don't hear, oh, he said it's okay, I'm going to go increase my intake. Paul, cannabis is one of your favorite subjects. Along with gabapentin, Paul recommends it to all his patients.

Sure. Well, I mean, there's that, you know, side note, but like the sort of recent analysis suggests there might be some cardiovascular risk with that. And that being the case of if heart health is literally healthy, then we should probably not be wildly enthusiastic just yet about recommending it. Yeah, so I don't recommend it per se. And then herbals comes up a lot. And taking a detailed herbal history, people try all sorts of liver supplements. And so I think it's important to ask about...

supplements in general, you know, for their health. But in particular, once people learn they have hepatitis B, they often pursue herbals. And unfortunately, there's not really one that I could truly recommend. You know, there's... probably some truth in it you know some herbologist centuries ago figured out something for instance with milk thistle there's there's some truth there but when you take you know the average formulation that you can get here

you know, the studies are not really showing a positive effect. And so there's probably a better use of the patient's money. And then the one thing that might be good for liver disease and for prevention of liver cancer is coffee. So, yeah, it's observational data. And perhaps, you know, our priors, you know, most of us drink coffee as physicians, you know, our priors are maybe a little different. So we may, you know, be quick.

to look at the literature positively. But so, you know, when you're a doc and you're constantly telling patients not to do things, it's kind of nice to say something that's okay. I'm not going to accuse you of pandering, Arthur, but Paul...

Paul and I are huge fans of coffee, and we've given coffee a lot of good press over the years, Paul, haven't we? We're reducing AFib. We're preserving livers. We're prolonging mortality. If you're looking for a miracle drug, coffee is it. I don't know what to tell you. And then vaccination. I think hepatitis A becomes an indication if you have liver disease. And if you have advanced fibrosis or cirrhosis...

It's an indication for early pneumococcal vaccination, just as a reminder. So these are all ways we kind of can mitigate not only liver disease, but just sort of, you know, apply the healthcare interventions that may be helpful.

All right. We do want to get to talking a little bit about treatment. So, Malini, you want to read the last part of the case and then we can talk about treatment a little bit? Sure, yeah. I think to start out, I would love your framework in terms of when, in terms of referral, do you think primary care providers should be directing patients towards a specialist as we're thinking about getting to treatment?

Yeah, I'm hearing on this call that referral for chronic B is the answer. You know, there are definite primary care practices that see such a high prevalence that they've become extremely comfortable with. hepatitis B. A good example is around the Bay Area. There's some practices. There's one led by Amy Tang, who's been so prominent in sort of leading a primary care approach to hepatitis B. Su Wang over on the East Coast. These are all people who've really

integrated into their care. But that's not the usual case. And so I'd say for most, you can refer, although, you know, just like patients can get fatigue to come to their specialist twice a year and whatnot. So sometimes if the... primaries willing, we can kind of

share visits and have labs perhaps at their yearly physical one time and then see me in between. That way we're kind of working together to minimize visits. So there are ways that we can collaborate with our primary care colleagues to kind of make it simpler for patients. And then we talked a little bit about treatment. And so once a patient has cirrhosis, we generally treat with antivirals pretty much for the rest of their lives.

But then earlier treatment, we do consider in those active phases. And so right now, the guidance by the American Association for the Study of Liver Diseases, double ASLD, put together an algorithm with hepatitis B DNA and ALT and, you know, just... come up with a variety of criteria to treat but in general one should think you know alt elevated especially two times the limit of normal one should treat they also use a lower limit of normal

upper limit of normal than what you'll see in your lab. So just so you're aware that upper limit of normal has crept up over time. And so they want people to be aware that one should use a different threshold. To remind the audience, we had a liver prof on Scott Matherly, and he was telling us that for women, he considers 20 to be the upper limit of normal, and for men, 30 to be the upper limit of normal. And people with levels above that, you should consider abnormal.

And you can work it up as you would anybody with elevated ALT. Yeah, that's absolutely right. Can I ask my patented Paul Williams standard issue, stupid basic question, but what... Why the delay? I understand treating when someone has evidence of active inflammation, but you say usually once someone has cirrhosis, that's when you consider treatment. That feels a little bit like...

locking the barn door after the horse has been stolen? Like, what are we holding on to? Is it a matter of toxicities of medications or what's the rationale behind that? Okay, yeah. You know, this is actually a fundamental question to hepatitis B that we're still trying to sort out.

So the argument against treating everyone is that some people will move through these phases sequentially. and will do fine and will kind of clear on their own. And we actually don't know what will happen to them if we interfere early with treatment. And so what we... you know what i mean are we interfering with something that actually works out okay for a lot of individuals so take acute hep b for instance in an adult you know you're 95 likely to clear it

And so while it seems like, oh, you have an acute virus, maybe we should treat it. We don't actually know if treatment is going to like do something to interfere with overall what a good process is. And so chronic hep B is not 95% good, but. So that's one idea. And then also once you're on treatment, if you come off treatment, there's actually an increased risk of flares. And so there's potentially harm, particularly if the patient doesn't stay on the treatment.

Now, there is an argument on the flip side. You've brought up a hot-button issue. Should we just be treating people earlier and not going through all this rigmarole? And there are definitely advocates on that side. You know, I'd say our ID perspective, there's prominent folks who are like, well, it's the virus, stupid. We should just shut it down and keep it shut down.

So that's an HIV approach. It's a hep C approach. And so, you know, I still think this will be worked out in the coming years. And right now, the Liver Disease Society is in the process of updating some of the guidance around this. And internationally, people, we mentioned this briefly at the beginning, but internationally, guidelines are moving to more simple. You have the virus, hey, let's just treat. So you're actually onto something there. Oh, great.

Every so often. Yeah. I mean, with hep C, people can be cured, so they're taking 12 weeks of medication or 8 to 12 weeks of medication and then stopping, right? But with HIV, you have it, you stay on the medication. get your viral load undetectable, and then you can't transmit it to others. So this may be going that same way is what you're saying. And the medications, so it's tenofovir and emtricitabine.

The two different tenofovir and emtricitabine are some of the ones, and I think there's still interferon. I still saw in some of the articles, I'm not sure how much is being used. Can you talk a little bit about that? What it's like for patients to be taking these meds or the side effects, a big issue for them.

Yeah, no, I think you had a recent podcast on PrEP, right? So, my buddy John Wong, great guy. So, it's tenofovir and entekovir, actually. Entekovir, I'm sorry. Although you are correct that mtracidibine…

also has activity against hep B. So you've lucked into an answer there, but no. So the old drug was lamivudine, right? And so m-tricitabine is kind of a modern... version of that and then we have entecovir which again an antiviral these are all polymerase inhibitors and then we have tenofovir and we have the two formulations of tenofovir

broxulfumarate and the alefenamide. And then for PrEP, you're using two agents, right? You're adding in the emtricitabine. So basically, we use entecovir or tenofovir in this country. for treatment. And what to know about those are, well, they're generally very safe and you can maintain them long term. There are warnings about lactic acidosis, but that's generally for sick patients and not so much in the healthy patient. And then for tenofovir, the two formulations, I think this was well...

covered, I think, during that prep episode that I listened to preparing for this call. What a great guest, Paul. I just have to say, yeah. Does the homework all. It's amazing. Well, you guys have a great thing going here, but the tenofovir alefenamide, you may remember, that's the one that has less effect on kidneys and bones. Unfortunately, it's more expensive, and so I try to get that for people who are older, who are at risk, post-menopausal women, etc., and sometimes I can get it approved.

But otherwise, for younger patients, the TDF is a very reasonable choice. And the reason why a lot of people like tenofovir, it's got like the highest barrier to resistance. You basically don't develop resistance. And Tekavir, to be fair, does have a high barrier, but you can develop resistance, particularly if you're kind of not taking it perfectly. And if you have...

Prior lamivudine exposure, you might have more chance of resistance and you need a higher dose of anticovir. So tenovivir is in some ways simpler for many of us. And so, you know, like many things, the answer is whatever the insurance will cover. All right. I'm glad I made that mistake. It's a good teaching point for the audience, Paul, and me, of course me, but the audience too helps me remember my mistake.

Probably intentional. It was actually, that's really nice work. That's nice of you to suggest that, but it was not. All right, let's read the last part of the case, and then we can, you know, we might have a couple questions left, but I know we're running short on time here. All right. So let's say our patient doesn't have any evidence of cirrhosis. He's hepatitis E, antigen negative, has hepatitis B.

DNA of 4,200 and ALT of 77. So based on that constellation of hepatitis B, DNA, and ALT, we do decide to initiate antiviral treatment. And let's say for the sake of this case, we are treating them with TDF. So one major... question that comes up that seems like it is somewhat controversial and maybe patient dependent is what our endpoints for treatment are and how long should we be continuing treatment? And so how do you go about approaching that question? Yeah, well...

try to keep this relatively simple in that most patients who start therapy will remain on therapy for a while. There are options to stop therapy if they pass through a phase of seroconversion. For instance, if you start when you're e-antigen positive and you pass through that phase, perhaps they could be one of these folks who, when you take things off, they have a low viral load and normal ALT and you can leave them alone. They just really need monitoring. And then for this gentleman who's...

already E antigen negative, some folks as they go on treatment will also convert their surface antibody. And usually we wait a year to kind of consolidate that, but then you can... kind of potentially stop therapy. And their risk for cancer goes way down if you can get them both DNA negative, which the drug accomplishes, and then the surface antigen goes negative. But most patients will stay surface antigen positive.

awesome outcome of what we call functional cure. Only happens about 1% per year for folks. But we do look for it because it does change management and it does improve prognosis. And so the general monitoring is every six months for our DNA. for ALT, potentially safety labs for renal dosing of these agents. And yeah.

And then potentially rechecking for fibrosis progression. Although actually they've shown fibrosis regression on long-term treatment. There are good outcomes with these agents. And then just briefly, I do talk about novel. So... You may have heard of HIV cure. There's a lot of excitement. Can we do something to make it so patients don't need that lifelong medications? The same process is going on for hepatitis B. And so that may be the future, probably years.

Maybe decades down the line if you're a pessimist, but there's a lot of interest in this space. Just get AI working on the problem. It'll be done in like a week. Sure. Yeah. Okay. Just repurchasing, you know. Repurposing colchicine dosing and proxone, but I'm sure there's going to be. Or maybe you should get Ben from Parks and Recreation to work on the problem. He sounds really smart. Yeah, there we go. Some of his accounting friends, yeah, they'll figure it out.

I wanted to ask about the, because you mentioned that hep B, even without cirrhosis, you can get hepatocellular carcinoma. So what's the screening like for that in the long term, like these patients, once we identify the case of chronic hepatitis B? Yeah, so for chronic hepatitis B, screening with an ultrasound every six months, with or without an alpha-feter protein, and then the...

Incidents in lower viral load patients can be lower, so it does relate to the level of virus. If they have smoking, alcohol, diabetes as a risk factor for liver cancer. You may want to screen a little bit earlier than the usual age-based recommendations, which are basically age 40 for males. since their risk is higher, and then age 50 for females. And then we talked about hepatitis D. If they happen to have that as well, we would institute screening earlier because that really does...

throw fuel onto the fire. And then finally, family history. I almost forgot family history. If they have a first degree relative with liver cancer, you'll start screening much earlier. And what I tell patients, their ultrasound's kind of like a twice a year mammogram of their liver.

It's not a perfect analogy, but most of the time things will be perfectly fine. But if we find something early, we can really intervene and a smaller cancer is so much easier to deal with and easier to cure than a late presenting one. Yeah, I find it challenging to get the twice a year ultrasounds on patients. If you don't have a system in progress, I feel lucky if I get it done once a year, to be honest. I think it's just hard with everything else people have going on.

But I'm not saying I'm not going to try to do it. But if someone's 50 and you're starting to screen them and they live to 80, that's like 60 ultrasounds they're going to have over the course of their life. It's a lot. I know. Yeah, I've discovered a lot of gallbladder polyps and things this day. So, you know, there are some costs of screening. But in the end, you know, the doubling time of liver cancer is within months. And so that's why this sort of every six months.

cadence is kind of a well-known thing amongst liver specialists and liver cancer specialists. Well, I think this has been great. I'm going to ask Paul and Malini, either of you have any...

Any other last-minute questions before we go to take-home points? Because we have to, at some point, let Arthur get back to his night here. I feel great. I think we've covered a lot of ground. I feel much more comfortable with this tonight. Okay. So how about... one or two take-home points that you really want the audience to recommend about this topic, and then we'll let you go. Well, I think one of the themes is that hepatitis B... is a strange virus and it converts from like...

stable phases to these sort of whacked out dynamic phases. And that's why we got to follow patients and be sure we properly stage them and know what's going on. And we don't miss that sort of silent disease progression. And ultimately, it is worth it to screen individuals and vaccinate. I think we don't kind of see what we prevent, but...

A well-followed patient with hepatitis B generally will have very few complications. They'll get on treatment early. They'll have a lower risk of liver cancer. And if it develops, God forbid, but it happens, you can deal with it.

with it earlier is much better than later and so you know it can be you know pretty rewarding and you know those outcomes that you'll never see you know that's that's that's one of the joys of primary care is to kind of think hey you know we did some good here so I like that. We don't see what we prevent. Arthur, you plugged the University of Washington primary care guide for this, but anything else that you'd like to plug before we let you go for the evening?

No, I hope people will find on that University of Washington website. Again, it's funded by the CDC and done by some really great colleagues. really a ton of teaching on hepatitis B as well as hepatitis C. And so you'll find modules on each of these topics there. For any deeper dive into how to stage liver disease, all the calculators that we kind of mentioned earlier, it's all there. So I hope your listenership will find those useful.

This has been another episode of the Curbsiders, bringing you a little knowledge food for your brain hole. Yummy. Still hungry for more? Join our Patreon and get all of our episodes at free, plus twice monthly bonus episodes at patreon.com slash curbsiders.

You can find our show notes at thecurbsiders.com. It's time for our mailing list to get our weekly show notes in your inbox. This includes our Curbsiders Digest, which recaps the latest practice changing articles, guidelines, and news in internal medicine. And we're committed to high-value practice-changing knowledge, and we want your feedback, so email us at askcurbsiders at gmail.com. It helps a lot when you subscribe, rate, and review the show on YouTube, Spotify, Apple Podcasts.

A reminder that this and most episodes are available for all health professionals for CME through VCU Health at curbsiders.vcuhealth.org. I want to give a special thanks to our writer and producer for this episode, Dr. Malini Gandhi, and to our whole Curbsiders team. Our technical production is done by Podpaste. Elizabeth Proto does social media.

Jen Watto runs our Patreon. Chris the Chew Man Chew moderates our Discord. Stuart Brigham composed our theme music. And with all that, until next time, I've been Dr. Matthew Frank Watto. I've been Malini Gandhi. And as always, I remain Dr. Paul Nelson-Williams. Thank you and goodbye.