Drs. Ward, Shiffman, Gutierrez, and Kowdley answer questions from course participants.
I'd like to invite uh our other speakers to join us. Now in the panel. Dr ward and dr cowardly as well as dr gutierrez and dr shipment. I'd like dr fernet also to join us that she's co moderator and will come up with some questions. So for any of you in the uh audience, if you'd like to ask questions, please uh send them to the chat box or ask a question. And while you're doing so, I'm going to start with a question with Doctor Doctor cowardly about the new labelling for folic acid. I think that's timely and important. So, um, you know, there's so sort of what's happened with the Vienna colic acid is the same issue that happened with protease inhibitors for uh Sirat IX that had first with protease inhibitors. First erotic, they were contra indicated in the compensated Sirat X. And then we got a warning letter from the FDA and we were worried about using PS and see erotic. They have more hypertension um, with Pepsi. So now with the Bennett folic acid and got the same thing. So clearly there are indications for endoscopy for viruses Um in any Sirat IQ that has a publish can score of 20 or greater or platelets less than 150. So let's say you got a PBC patients um That's not it's got an inadequate response two or so. And you want to put them on earth. So you want to put him on a pinnacle Cassidy? They've not had a biopsy. Platelets are okay. Um 6% of those patients can have viruses without cirrhosis. As you know. Um Are you gonna endoscope that patient before starting them on? I'm gonna call cast. Yeah that's a good question. What we Clearly understand is that portal hypertension in the absence of cirrhosis and PBC is number one uh infrequent if not rare and the ideology is not related to fibrosis. They may have some variant of modular regenerative hyperplasia. They may have pre hepatic portal hypertension. Some of them have undiagnosed portal vein thrombosis. Some have even postulated that the large lymph nodes in the port of iapetus might compress the portal vein and increased portal hypertension. Uh There's really no evidence that the problem with safety of a better colic acid is related to Puerto systemic shunting. It's really about the fact that this is a steroidal bile acid therapy, bile acids undergoing entra paddock circulation and um and bile acid exposure is significantly increased based on patient's underlying liver function. So there's no reason that a patient with non psoriatic portal hypertension that might result in various is would be at any increased risk with Osaka. And so I don't think they're endoscopy is needed routinely as long as the patient has been clinically assessed and in fact um very nice poster presented at I. L. C. 2021 examined predictors of outcome in patients with PBC And a platelet count greater than 150 uh compensated liver disease with no sentinel events and normal liver function uh really did not associate with any increased risk of complications. And as you may remember from the PK studies the distribution and exposure levels in the liver and systemically with O. C. A. Is so much higher only in patients with child Pugh. Class C cirrhosis. It is definitely increase in child Pugh B but dramatically increased only in child you see so to me a patient with and billy Rubin that is say less than two. Um And no evidence of cirrhosis uh and no obvious evidence of a paddock encephalopathies. Societies et cetera should tolerate this drug quite fine. Um The more important point I think is that the use of OC. A. In patients with cirrhosis where there's a question of whether or not they have clinically significant portal hypertension should be made. That decision should be made in conjunction with the pathologist like ourselves and those who have expertise in treating PBC. And in fact, you know I think we all have patients who have quote unquote child Pugh B. Cirrhosis where they may have uh they may have benefited from O. C. A. And I have several such patients that where I am convinced I was able to hold off liver transplant evaluation. The last thing I'll say is that from this large population based study, what's clear is that uh the patients with child Pugh A with five points is very different than child Pugh A with six points. And the patients who have a six if you will behave more like patients with child Pugh B. Or d compensated cirrhosis. Whereas patients who have child Pugh A five behave much more like patients who are non erotic. So I would say look at the platelet count, evaluate the child Pugh score, see if the patient is five points or six points and if they're a five cirrhosis or if they're non erotic they should be fine. Thank you for adding in the, I'll see data. I want to point out that the easel meeting for 2021 was held this week virtually and just ended a couple hours ago. So I didn't demand any of the speakers update their slides for those. But I did demand that tomorrow mary Rinella update her slide deck for uh dance because I think it's so critical. But if any of you are aware of what was presented at easel on your topic and you want to time in, that's great. I have two questions I think for both for dr Shipman regarding hepatitis B one is do you need Hepatitis B vaccine when you have resolved hepatitis B infection? So I guess somebody's Already had a dane particle infection. Do they need hepatitis B vaccine? That's number one. And then number two was what is considered two times ever limited normal for women and men when you made the criteria for ah antiviral therapy. So we'll take the first the vaccine question 1st. When you resolve hepatitis being developed surface antibody, you are when you resolve hepatitis B lose surface androgen and developed surface antibody. So in the absence of a discordant variant or in the absence of Co infection with two strains. So uh you're basically protected for hepatitis B A. Lifelong and you do not need uh any vaccination at all. I think the issue you're alluding to is the patient that is found to be core antibody positive, isolated who had Hepatitis B a long time ago. May or may not have known about that. And now the Hepatitis B surface antibody is not detectable. If you give that, if you give that patient one dose of vaccine, they will have a super therapeutic response. The surface antibodies will appear in very high tigers very quickly and if you continue to follow them out, what you'll see is that surface antibody level will decline again very quickly and may actually become negative within a year. That patient already has a agnostic response and does not need to be uh re vaccinated repeatedly. Just like somebody we know that has been given Hepatitis B vaccine and their level of detection of antibody falls below um falls below the detection level. They don't need to be re boosted all the time. The problem is you don't really know if they responded or not because we don't check people after they're vaccinated. So the this scenario is a health care worker that's presumably been vaccinated. They get exposure. They go to employee health and they're found to have no hepatitis B surface antibody. They should be given one dose of vaccine and see if they respond. If they do respond, they're fine that admit agnostic response. They can produce surface antibody when challenged. And again if you follow those patients they're going to lose surface antibody. Then the C. D. C. Does not recommend that they continuously get reboost it all the time just to keep a detectable antibody level. Good second question has to do with uh what is a normal adult? Well a normal adult is not what your hospital or your laboratory defines as a normal adult. What your hospital defines as a normal a. Lt is they take 10,000 consecutive patients or some number. They then draw a line at two standard deviations above the mean. And that's what they consider a normal value now for many hospitals that have liver transplant programs and see a lot of patients with chronic liver disease that results in a very high mean value because they have a lot of patients with elevated liver enzymes. Um And so what happened actually at our facility here just recently is they suddenly updated the normal value for A. L. T. So before I opened liver institute of Virginia in the community. The normal A. L. T. When I first started was 35 it suddenly jumped to 60 uh when they updated the numbers. And so we went to pathology and we said they can't do that you can't define the normal. The normal A. L. T. Is really 19 for a woman and 25 for a male. And those are the numbers that we should keep in in our head as to what is normal. And so two times that Is um 38 and 50. Okay. Very good. Thank you. I have two more questions. Quick ones for doc Doctor gutierrez first uh says what is the role of madras score? If you're not using corticosteroids, could you repeat that? What is the what is the role of the mad rescore if you're not using corticosteroids? You know I think the role is really to give us insight into the into the stage of the patient. Were clinically familiar with this as being a high risk situation. So if you see a patient where the madres has gone above 32 that should be a clinical indicator to you that the patient is indeed very sick And it could be getting worse. Um you know I think the Lily score there's some pitfalls of using it a day seven including the lack of it being a dynamic score. Um and you know you can also use your moderate score again at day seven or the early change in billy Rubin level which is what most experts recommend that and that really can give you an idea more of the dynamic improvement or worsening of your patient. So I like to keep the those scores in mind. Um You know throughout the course is I'm taking care of the patient. Really? Okay and chris there's a question what is the dose of Ben's it vibrates so that clearly that that person, mm not aware that bends it vibrates. Not approved in the U. S. So maybe you can clarify where that stands. Yes. So better vibrate is available in japan and is available in the U. K. I mean in the EU. Um and in fact has shown some promise and generated a lot of interest. Uh And there was a new England journal paper with christoph corpus show showing uh fairly impressive results with Visa vibrate uh compared to placebo. Um And that was within the last couple of years. Um patients had earlier stage disease in that study. Most of the other data with Visa have been relatively small scale studies uh And without really many much in the way of controls Fenno vibrate has been is approved. Um And um and it's a uh it is a and other fabric acid derivatives and final fiber. It is available in the U. S. Mainly to treat this lip anemia. But with fennel vibrate, it's also important to recognize that in 2020 the FDA issued a nous which is which is essentially a statement when they see uh new uh potential complications of special significance uh N. I. S. S. And uh and and and that was related to the fact that in liver disease you have to use this with caution other than for patients with fatty liver. So both Bessa and Fenno have black box or at least warnings regarding patients with liver and kidney disease and fiba rates as a class as you know, do elevate the creatinine levels. So it's important to keep in mind that the visa is not available in the U. S. And finally vibrate also has a potential warning with regard to using it in patients with liver disease. So off label use has been done and there are a couple of centers where fennel vibrate is used with with more enthusiasm. Uh and I think in the right hands it's definitely uh reasonably safe drug um as a second line option. But I would encourage, you know, if you have patients that are potentially candidates for clinical trial uh that they should they should try and find one of these two phase three trials or several other phase two trials that are currently undergoing um so that we can gather more evidence about the efficacy of these additional therapies. So if you use for unified, great uh dress in any of your patients, what does do you start with? I have not used to vibrate. Is anybody? Uh huh. Carrie mitch. Yeah, I've used it with someone that also had concomitant nash. And I started very very, very low, like the lowest I could go. I've used it in a half. A dozen patients chris that have not been able to take a pinnacle of gas. It started the lowest dose with that same warning. So the question on the venza fiber, it was actually asked by my P. A Yuki rosen carter who was japanese and she has, she wants to know what dose was used in the bends of vibrate study in japan chris. I do not have the answer to that because that was a a retrospective cohort study of people that we're adding. Yeah. So it's not a randomized controlled trial so it could. So the dose was not available john before we ask another question, you're you're on mute just to let you know uh john ward. But I had a question if you if you're aware of anything new that was presented at easel on eradication that we should know about. There were there was, but I didn't organise any comments about that so I can't really how about anything in any specific manner regret that okay, you'll let us to know if there was like any important follow up studies or or any anything else carrie. Um, yeah, actually I have a question for john on that. So I guess my, it's a double part of question number one. You know, why do you think the US is so much farther behind other countries? As far as eradication And for those of us who are sort of sitting in an office waiting for patients to come to us with Pepsi to treat them, what can we do to get better with the hep C elimination effort? Well, thank you for that. Uh, I gave you a few notable examples of some countries that really put, um, uh, the pedal to the metal very early on for a variety of different reasons, sometimes incentivized by public private partnerships with uh that made drugs more readily available. So that was the case in Georgia. You know, one noble exception about one noble example of some new development coming out of easel but also recently published was the really the achievement of elimination in the country of Iceland, which will be it is a very small population. But they again put all of the essential elements together of political commitment, right financing, uh clinical capacity building outreach to the target population together and to expand setting goals that could be measured a progress toward. And they they put together an effective program. Um You know, then with Egypt really being a very remarkable example of a very high prevalent high population country achieving that. You know, all that being said. It's not like you know the U. S. Was LTD at the outset by the high cost of therapies which then resulted in big barriers being put up. Big big very formidable criteria being put in place to limit access to those therapies. So that really slowed things down to begin with. So that's gradually improved over the last 3-5 years as I highlighted. And we did see start seeing and I think also our systems fairly complex, multi sectorial. So you have public private different insurers with different requirements. Um So that takes a while. Um and so you sort of took a while for those testing guidelines which multiple studies showed can be readily implemented. It just took a while for them to be routinely implemented and you began to see some increase in their use and then and then treatment people are getting treated. So you know I don't know if we're that far behind the world, certainly. I still think we're sort of in front of that, but there's, you know, some other countries like the UK which has done a very good job and so I think we are doing a good not great job of getting people tested and treated. Um I think we have a and I think once people are diagnosed there's fewer barriers than there once were if they get in front of a provider that it feels comfortable providing treatment including in the non specially setting. I think that from the biggest challenge for the U. S. Going forward is scaling up testing. Uh huh. Keeping this, keeping the visibility high for hepatitis C. I mean it's got to be such a fairly straightforward disease to treat that. I think many people feel like the problem solved when it actually it's not. Um, we still, so we've got to continue to focus on testing and these all adult guidelines. Uh, um, it's really what I call a safety net policy where you just want to make sure that you're not missing anybody, but you still need to be focusing on the populations at highest risk uh, to make sure they're getting the treatment or the most marginalized. So it could be racial and ethnic disparity of people such as african americans have twice the mortality than white americans. You want to make sure those populations are being served. Obviously, people inject drugs they incarcerated by extension. All of them need to have special programs for them to be getting the services that they need. So it's that, that that continues to be really, really important. And I think the, um, you know, for your question about Hepatology pissed, you know, making sure people get treated we need, you know, that continues to be critically important and for your own practice. But then also Hepatology, just being there and being available on a referral, even if it's a sidewalk consult uh for others to begin to feel comfortable because they have backup for those that minority of patients that still need referral to a specialist. And I uh, so we've seen a decline in mortality, but we still have about 14,000 deaths from hepatitis C every year that's reported. Um, and I would really would be interested for those on the call and those in the program. I mean, who is still dying of hepatitis C? I mean, I've been listening to this program, which I greatly benefited from, but it just really almost against, highlights how how relatively simple hepatitis C treatment is now, certainly compared to the other diseases we've been talking about today. And I just feel like no one should be dying of hepatitis C anymore. You want to answer that? Yes. Program. Only people that we've really been transplanting from Pepsi are the ones that get cancer and it's cancer often times after they've gotten treated and cured, you know, 257 10 years ago and now they are coming in with cancer. And I also in our cancer program, we're seeing a lot of patients that were treated many many years ago and then were lost to follow up and weren't getting their screening for their cancer development and now are coming in with very advanced disease and dying from cancer. And I still consider those patients dying from Hep C even though their hips he's cured and for that was years ago, but it's really quite heartbreaking when that happens. You've seen any patients dying from hepatitis C alone. I'm seeing patients, you know, one of one of my tasks at scripts health is to cover one of our underserved hospitals, which is in downtown san Diego. So actually frequently see a patient in shock, um, and multi organ failure in the intensive care unit whose positive for hepatitis C uh, to the disease. And, and I may be at least once or twice a month and see if I have another cohort of patients who don't have a phone. Um that I've been trying to treat for the hepatitis C. They will die of cancer. That's difficult to manage as well. So I think we're we're really not able to make progress. Is these underserved patients who have lack of access to medicine? Mm hmm, difficult to engage in care. No, it's easy to do mitch you've seen this? Yeah, I I agree with all those comments. It's the two groups that you see are those that were cured of their hepatitis C when they had cirrhosis. And then they don't get appropriate screening for whatever reason. Either their reason, their fault or the physician that was following them or told them they were okay and they were cured and they didn't need follow up. We certainly see um those uh those come in there is still a pocket of, you know, baby boomers that are older age group that we still, occasionally they come into the hospital and they test positive for hepatitis C. They still never known it. And uh, and then we get them in for treatment so that that still occurs. It's not very common, but it still occurs. Um, and like Julio said, uh, the inner city underserved poor access to health care. Don't know they have hepatitis C, although they have all the risk factors. Um you see some of those as well, but the vast majority of Hepatitis C. Nowadays, these young uh kids or young adults that find out they have hepatitis C when they enroll in drug treatment. Um they are easily treated and easily cured. Sure, chris Yeah, no, I agree. I think the challenge is really the patients that have poor social support, um difficulty getting access to the drug. Uh and and and those kinds of challenges which you know, increasingly what we're seeing is that a common theme in terms of what we spend the majority of our time talking about and liver transplant selection conferences, at least at least at my center. So, you know, that's a big challenge and it speaks to disparities in health care and everything else that we're seeing today, but but certainly I would say I would agree completely with john I do not remember the last time that a patient that had, you know, hepatitis C related d compensated liver disease And had a meld greater than 20 um was presented at a selection conference. Right? I agree. We haven't we haven't sent a patient for transplant for run of the mill hepatitis C decompensation and probably eight years. That's really interesting. And and with the Kerry's comment, you know when we were thinking about tracking progress store that these elimination clothes which include mortality, one of the questions was, well if someone dies of hepatitis a liver event after cure, do we do we count that as an HCV related mortality? Meaning you're not making as much progress as you are? You know, you might otherwise score it if you will. So it sounds looks like the carries point of view that should still be regarded as an HPV related death rather than a absent HCC surveillance, for example, got it personally would have the same problem as uh counting those patients that die of an Emmy as a covid death. Right? Hey, john, what is the prospect for a national initiative for needle exchange and endorsing matt as opposed to statewide initiatives? I think this is the single biggest reason that europe and Australia, in my opinion, have done better and we have not done. And it's sort of, it's sort of ironic, isn't it? Because on the one hand, arguably the greatest success in eliminating hepatitis C uh, in the U. S. Has been the V. A. Which is a national federally funded program, but at the same time, the lack of, you know, national priorities and uh, an agenda for needle exchange and other types of um, harm reduction maneuvers, as opposed to, uh, sort of these old fashioned approaches have been some of the greatest impediments, in my view. No, absolutely. Um, and Australia, the Netherlands or two examples of countries that have very good coverage. The UK is certainly getting their terms of harm reduction and then related hepatitis testing treatment as part of that. You know, we're inching toward that. I mean, when I started being the division director in 2005, you could not even go to a conference that was on the subject of harm reduction for people who inject drugs because of the federal restrictions and had persisted for quite some time. And so it's been very much a, you know, inching forward toward better practice. You know, while we were waiting for this, waiting for, during the, during the, during the break, we were laughing about how, uh, Winston Churchill quote that you know, us will always do the right thing after they've tried everything else and I'm afraid that's the case, you know? Here, as I noted, just uh just this year for the very first time, federal money through the Covid Recovery Act was made available to purchase uh safe injection equipment, people inject drugs. So that's 2021. Uh The V. A. Is starting a syringe exchange program uh in some of their uh centers to some of you on the call. Maybe in program may be aware of that. They're doing that very, very slowly, very thoughtfully. Just because of all the, You know, the points of view around around harm reduction. So hopefully that will begin to accelerate. But I agree with you. Chris is something that we we need to get up to scale it up to this 2200 level access that we proposed now about three years ago. But we need to get there. We're going to really be serious about eliminating hepatitis C in the country. Uh Two more brief questions. Chris just a yes, no philadelphia and L. A. Fibrin or you mentioned are Have some early Phase two data That's convincing for PBC and are now in Phase three. Any reason to study those in PSC? Yes. Okay, there's your answer. Uh That's what I thought too. And mitch you didn't talk about stop nuke um Strategies for e energy negative patients that do not have cirrhosis that have been on a nuke for at least 36 months that have normal liver tests and undetectable DNA. And this has now been data that's accumulated. It started in asian countries, then it came from europe. And now we've got a strong publication from north America from Toronto suggesting that you can predict patients that we'll have a chance for losing surface androgen and being off a nuke if they've got a low tighter of hB circumstances and tighter. So question for you. And then all the panelists are you checking hepatitis B, surface damage and tigers and second are you talking to patients are considering stopping the therapy? So uh yes, there is data accumulating that if particularly in the anti negative patients That if you keep them virus undetectable for several years and their surface androgen level falls below 100 that they might be a good candidate where they could come off and remain in a functional cure, so to speak with undetectable virus. However, there is a relapse, right and you still need to continue to follow those patients. Um, and um I think it's easy for those patients to hear that they are cured. They don't need any therapy and then there's a danger in not following them or the patient not following through because they think they're okay. So in my own practice, we keep those patients on therapy, um, and don't kind of rock the boat. I think what you do in clinical trials where you can carefully follow these patients, um, is one thing, but I think in practice, um, it's easy for the patient to get the wrong idea and not continue to follow up and not continue to get their cancer screening. Well, unfortunately, I don't think there's gonna be a clinical trial because this is not going to be supported by. Yeah, I don't mean clinical trial and the pharmaceutical center. Clinical trial. Just large cohorts being followed by individual, gonna have to be the hefty NIH group, chris cowardly. You're on that group where you've been on it, the hepatitis B NIH group. And are you checking surface engine tigers? Are you stopping nukes? And what's what's the Yeah. I think the role of surface and edge and tighter is useful only when it is accompanied by um you know, maintaining suppression of H. B. B. D. N. A. Uh and in the setting of E. And again to e antibody serial conversion. I think the um I think the whole issue of uh surface antigen typewriters is very much dependent on the fact that in my opinion, um you get a more robust suppression and a sustained suppression of surface and edge and tigers with um with interfere on the problem with the problem with looking at s androgen levels and using that as a treatment as a as an endpoint in clinical trials with antiviral compounds. As I think we're going to start seeing escape mutants to surface. As mitch pointed out in his talk and then we're going to be stuck with patients that may have low or undetectable s androgen levels, but still by remick. Um but but that's just, you know, a very high level opinion from me in clinical practice, I don't usually measure surface and it entitles, but I think that it can be useful. One thing that I find really interesting and I'd love to get comments from you and mitch is uh you know, it seemed like there were back in the lamiVUDine days, it seemed like we were able to achieve um you know, sustained viral logical response and get people off of drugs more successfully than we are Now. That's just my anecdotal observation. And if you remember in the in the paper that I don't know if either of you are co authors jewels. Dean Stock was the first author. I was a co author on that paper and the three year follow up study with lamiVUDine In patients that had that consolidation phase had achieved the so called 3.0 conversion, lost the advantage and gain the antibody and remained undetectable for DNA for quite some time, something like 60-80%, of those patients at three years remained uh in that phase did not reactivate. But I found in my clinical practice um that when I follow those rules, eventually, many of these patients with the newer antiviral drugs seem to relapse. Is it just my anecdotal experience or have you noted that as well? And if so what could be the reason? I've noted it as well, But I think you and I treat the same. We're in the Western United States. I think the majority of my patients are asian, which would I would assume to be true for you too chris and the lamb studies. So there early lamb study and the intake of er and to not study, you know all of the negative patients were in Greece. So they were caucasian. There were all the honestly study. That's why his first author on all the damage and negative studies. So so they and as you know that it's very clear that the chance of substantial loss and clearance is much better in caucasians. Probably a reflection of of whether it was vertical transmission or not. But that's been that was shown in the Toronto study as well. If you're caucasian, your D. N. A. Is less than 1000. Excuse me. Your surface engines less than 1000. Your chance of losing surface engine is better than 50% if you stop your milk. So I've actually talked to some of my caucasian patients about that, but most of my patients are asian and and I've talked to them about relapsing and the risk and all that stuff. So it's it's still an unknown but I think it's going to be done and mitch in the United States. I think there Nora Tarell starting to do this at USC and I think uh I think we need an NIH funded trial because I don't think we're gonna get a trial any other way unless it's NIH funded. It's interesting paul. I don't think I don't I was just I was just thinking, I don't think I have a single I have one patient who is who is from Italy, who has genotype d I don't think I have a single patient other than that patient that is non asian with a baby in my practice. We just got to do a question from the audience for Julio, can you comment on how prior bariatric surgery affects the risk for alcoholic hepatitis? Do you think they have bash or changes in alcoholic metabolism after surgery? Oh yeah. This is a wonderful question. Um and a clinical observation. I think by many hepatology pissed. The mechanism by which patients who have undergone bariatric surgery have more severe alcoholic liver disease is incompletely understood, but It's probably related to a couple of things. one absorption seems to be much different Patients and the absorption of alcohol may induce more severe fatty liver and indeed, we may see it in patients who had a little bit older bariatric surgery since the ruin why technique has changed a little bit after 2007. So you may see these patients typically with bariatric surgeon around 2000 or so. The second thing is, you know, the another thing that's incompletely understood, but the metabolism of alcohol very significantly amongst individuals. And the signals that cause addiction to alcohol maybe increase in these type of patients. That's the metabolites are a little bit different. So I think it's incompletely understood that we definitely are seeing it. And actually in one of our recent alcoholic hepatitis patients, there was a history of bariatric surgery. So, I mean, I think this is a real thing for sure. Carrie, you want to comment? You've seen? Yeah. We actually had a resident that pulled our again pulled our epic data using slicer dicer I think last year. Right. But it was during the beginning of Covid and we definitely see an increase in alcoholic liver disease in patients who had prior bariatric surgery. And I think, you know, just like we see, I think the last comment that Julio had was correct, that there is definitely an addiction personality. And we see alcoholic alcohol use disorder patients quit drinking and then become overweight because now they're addicted to food. And we see the same thing with bariatric patients where they have now substituted their food for alcohol. And I think that's very true. But I do think that there's an issue with absorption and they're also be maybe some mild malnutrition happening in the liver with all the weight loss after the bariatric surgery and the changes in their micro nutrient absorption that may increase their risk as well. The other thing. Uh huh. Forget alcohol. There's a lot of alcohol D hydrogen is in the gastric uh cells. And so drink I have a normal stomach. You're actually breaking down a lot of the alcohol before it even gets absorbed. And uh when you have a gastric bypass you're completely uh that's completely eliminated. So you're getting like a double shot instead of one. And I think we've got time for one more question. This comes from dr ward's carry some weight and I guess mistresses to you. The question is there's a move to treat all surface answers and positive patients because of simplicity in low middle income countries, Do you agree with this? Well the problem in treating all Hepatitis B surface antigen patients is that the vast majority of patients that are surface and again actually have inactive disease, they've already sero converted. They have low levels are undetectable D. N. A. And they're actually very they still have a risk of liver cancer. But that risk is very low. And nobody has ever shown that putting those patients on a nuke is going to lower their risk any lower than it already is. Remember if you take somebody with active Hepatitis B and you treat them and you lower their DNA to undetectable. They don't you don't prevent cancer, you simply reduce the risk of cancer. And so the question is, do you reduce it lower than natural serial conversion? Would we don't know the answer to that. My guess is probably not. All right. Well, I like to think this comment paul. My only thing is with in the U. S. You're totally right. But in low middle income countries where they don't necessarily have access to ongoing monitoring and ongoing labs and the specialists to help interpret these labs, you may end up saving lives if you just treat everyone. Because the drugs we have now are pretty darn safe long term. Um And just because you do have a really complicated step in the middle there. Yeah, I agree. I agree with you in those countries, that's probably correct. The question is um the cost of do the cost of drugs and uh the vast majority of people that are, so the difference between hepatitis C is number one finite versus long term. So the cost becomes exponentially higher. Um And you need some kind of I think you need some kind of assessment at some point on these patients, right? You still have a clinical care capacity problem, even if you're thinking about treating everyone just because the population uh so large. So but thanks. I really appreciate all those comments about that. Thank you. So I'd like to thank all of the panel members for an excellent discussion.
