Welcome back to those of you who came back after the break, the brave ones. Thanks for the committee for inviting me to come talk. This is a topic that's near and dear, and I think that I'm going to try to get through slides that you've already seen on prior talks quickly. I don't have anything to disclose, but if anyone's interested in my services, I'm happy to add to the slide later. The objectives today are, for me, are to discuss economic costs of obesity, patient outcomes related to obesity, treatment options, patient outcomes, and truly put that together to figure out when we should be utilizing bariatric surgery within our transplant patients. So if you all know this is K2, it's the second highest mountain in the Karakorum range. Only 75% of people who try to climb this mountain make it. 25% die. Higher death rate than its sister mountains. I look at this, and I kind of think that this is how we look at this kind of issue of obesity. There's multiple ways to get up to the top. We're all not going to make it, and we have to realize when we have to change paths because we're going to have to use multiple routes to get there. So I'll skip down to this slide. You've all seen these percentages before, but basically for us in Ohio, it was that in our primary reason for listing patients back in 2000, none of them was NASH, and it was already up in 2012 up to 25%. People have presented data that NASH will clearly become the number one reason for liver transplant shortly. Cost, just of obesity alone, not associated with anything liver-related, is $150 billion. This is back in 2009. $30 billion was just an additional cost per year of loss of time from hospital appointments and admissions to the hospital, things like that. Any obesity can cost anywhere from an extra $200 to $300 billion a year as we move forward within our healthcare system. When we relate the cost of obesity to liver transplantation, this is a nice paper out of Johns Hopkins, but when you look at obese patients, and this is about 120 patients and 21 of them are in the severe obese category, which was interestingly in this paper is actually only patients with BMI above 32 at this point. That was considered severe obesity. But even in that group, the 32 and higher, the cost was almost $30,000 more. Now this can be due to length of stay, post-op complications, ICU days, but what we all fall back on a lot of times when I have these discussions with others is that it's okay, we should be transplanting the obese patients, which I don't disagree with, because their survival is the same, which I also don't necessarily disagree with. But that does not mean that their impact on our resource utilization and healthcare system is the same. So when we talk about outcomes of liver transplant patients who are obese, this is over 800 patients at UW. They looked at even just the ones with Class II obesity. Those patients were found to have increased wait list times, decreased graft and patient survival, longer OR times, longer ICU stays, and longer length of stays. And this is just in the Class II obesity segment. Not only that, but we know that the access to transplantation, both for liver and for kidney, is decreased when you talk about patients who are obese. So your odds of receiving a MELD exception go down by 30% if your BMI is 35 to 40, and down by almost 40% if your BMI is above 40. Your rates of being turned down for an organ offer are above 15% higher if your BMI is above 40, and your rate of being transplanted is almost 30% lower if your BMI is above 40. So access to transplantation for all these patients, as much as we like to say that we don't change what our criteria are for transplant in regards to obesity, it's not the case, right? We kind of heard a little earlier that you might not take a macrosteatotic liver of 40% and put it into someone with a BMI of 45, but you may put that liver into someone with a BMI of 25. So right away, that's just one instance where that patient, they did not get that liver because it's strictly because of their obesity. Now, current NIH recommendations, I mean, for many of you will know this, and I've skipped over all the heat maps of where it goes from blue to red. We all know that obesity is rampant. It's an epidemic in the United States. The rates are still going up. It's projected that at some point 60% of the U.S. population will have a BMI greater than 30, 60%. That's two-thirds of patients across the country will have BMIs above 30. You can imagine what that will do to the rates of non-alcoholic fatty liver disease and NASH. Current NIH recommendations are anyone with a BMI above 40 doesn't matter what they have. They should have surgery. It doesn't matter what comorbidities. Anyone between 35 and 40 with two obesity-associated conditions, of which there are many, qualify for surgery. And as you heard earlier, there has been discussions, although they've been going on for quite some time, I think at least for the last five years with Medicare in regards to lowering this requirement, specifically in patients who have a lower BMI and who are diabetic because their mortality rates are higher. Now, that has not been enacted, but it's been discussed over and over. So why surgery? So when we look at medical weight loss therapies, we've seen some of the curves, and I'll show you some later too, that the durability of weight loss when done medically is not great. At around two years, you lose around 10% of your weight. At two years of your excess weight, that's with really supervised medical weight loss. Now, the durability of bariatric surgery is very different. You can still have approximately 50% to 60% of your excess weight off at three years. Now, these are the three main types of bariatric surgery. Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding. Gastric banding is truly not being done very much anymore, if at all, at major centers because it's not as efficacious. And for us within transplant, the last thing we want to do is put a plastic foreign body once we're going to give you immunosuppression, so we don't utilize it, and bariatric surgeons usually don't utilize this very much anymore either. The one that we utilize the most is sleeve gastrectomy because it doesn't have any untoward effects on immunosuppressive absorption, as gastric bypass can have, not always though. Again, just one slide on this because this has been touched upon before, but we do know in patients with fibrosis, not cirrhosis, but fibrosis, that appropriate and significant weight loss can decrease stage of fibrosis. So in this study, they found that 84% of patients after bariatric surgery had a resolution of steatosis, and those that had fibrosis had some resolution of that. This has been repeated over and over again. If you look through the bariatric literature in regards to whether it's roux-en-Y, whether it's sleeve gastrectomy, whether it's a biliopancreatic diversion, significant weight loss will assist you in fatty liver disease or NASH. So what I'm here to talk to you about is when do we employ bariatric surgery within our patient population, and for me, when I say our patient population and transplant, it means once the patients are cirrhotic. Just to kind of, one of the case reports that were just presented, I think the key aspect that we need to consider here and understand is that there's not one solution. So I'm not going to be able to tell you that you should do these three things, and the problem is solved. The key to this is to be able to understand that there's a spectrum of the patients that we need to treat with different modalities at different times and have those available. So a multidisciplinary approach is what's going to be key. But when we look at this, this is the pre-liver transplant. So these are cirrhotics. You can see there's not a lot of, this is from a recent article we published with Dr. Heimbach, a review article in liver transplant. There's not a lot of papers on this that we could find. But when we look at these, what we did find was that, this is one paper from Stacey Bretthauer, 23 patients, they had child's PUA, didn't have all the appropriate labs for us to calculate MELD, but likely low. Fourteen had Roman Myogastric Bypass. Eight had a sleeve. One had a gastric band. Important aspect of this is that almost 35% of those patients had a complication. So that's a lot, right, especially for a patient who's cirrhotic. So, and these weren't small. Leaks, strictures, both in the gastric bypass group and in the sleeve group. These are important things that can, if they happen, they can truly, in this patient population, can cause them to die. So what we did was we took those, at our institutions, we took these different papers and said, all right, well what group of patients seem to suffer the most? And these are our guidelines. These aren't ones that I'm proposing that you should utilize. But we do. And we, and what we, because we don't want to get into the arena of treating these patients and trying to help them and then hurting them in the process. So we use MELD, we will only operate on pre-liver cirrhotics, pre-transplant cirrhotics, if their MELD score is 15 or less. No real evidence of decompensation from portal hypertension. Now, I've broken that rule a couple times in regards to some patients with esophageal varices. So, but, you know, it is what it is. It is what it is. No ascites and a platelet count greater than 50,000. And I've been a little fuzzy with that rule myself, too. So, but we haven't gotten into any major problems with this group. Dr. Tanner hit upon this. I won't do too much on this, but Dr. Heimbach's group is, for sure, you know, has done the most combined and simultaneously, so simultaneously, we've got stretch and weak liver transplant. In her initial study, she had 37 patients who went through medical weight loss prior to liver transplant. And out of those patients, a weight gain to be a migraine in 35 was seen in 21 out of 34 of those after liver, after their transplant. And the 12 of those developed post-transplant diabetes. However, in the group that received a simultaneous sleeve with their liver, none of them developed diabetes. And what's interesting is when you look, when they updated their paper and had 29 patients, but also had 3-year follow-up, what they found was none of those patients developed diabetes either. And when we look at our kidney literature for in-sleeve patients, in all the patients out of 40-some patients that got transplanted, none of them developed diabetes after, who had a sleeve. None of them developed post-transplant diabetes at one year. Zero. So what we, and we heard already in the past, that diabetes is a major factor for mortality post-liver transplant. So if we can, if this is a really appropriate way to treat it in a specific patient population. Now, there has been some talk, we've talked about this complication rates and everything else, but when you look at this paper specifically, truly only one, two, maybe three of these complications are actually due to the sleeve and more of them are due to post-liver transplant population. So it's important to be really, you know, look at this paper appropriately. I think that their complication rate in their patients is actually really great. Okay. So this is, and you can see here, this is just kind of reiterating, this is the newer paper, that you can see that the blue line is the patients who did medical weight loss therapy, received their liver transplant, a lot of them regained their weight. Where you see the red line is the patients who had a sleeve at the time of their liver and they kept their weight off all the way up to three years. Now, when you look at these two groups, it's important to note that the diabetes in the liver transplant cohort versus the liver transplant plus sleeve cohort was statistically different, or almost statistically different, but half, and the same thing with the metabolic syndrome. So then when we looked at bariatric surgery after liver transplant, this is also talked about a little bit. I think someone had talked about the paper that we just published in liver transplant with 15 patients, and we'll just skip to that. What we found, all these 15 that we did post liver had NASH as their initial diagnosis for liver transplant. Many of them kind of presented it as a way that the case presentations were with slightly elevated liver enzymes, a potential biopsy that showed some stage of either fibrosis or some macrosteatosis already, and many of them were diabetic. What we found was in our patients, was that in the post group, obviously the BMI decreased. It went from 42 on average down to 35, but also our insulin units per day in the diabetics, they all went down to zero. All of our patients who had diabetes almost resolved their diabetes after the surgery. And with one year follow-up, we also were able to show that not only was the percent excess weight loss, but the percent of total weight loss was actually still very durable even at a year. We propensity matched all those patients to patients who had just received a sleeve and did not have a liver transplant in a normal population. And what we found was our operative time was fairly similar because one of the issues with this is people say that after a liver, this surgery is going to take a lot longer to do. In some patients, it does, but on average, it doesn't take that much longer. And the EBL was slightly higher at 50 cc compared to an average of five. We had no conversions to open surgery. Our length of stay was on average two days instead of one day, and 30-day complications are very similar between the two groups. Now, I just wanted to touch on immunosuppression because one of the issues in regards to what we're going to do here and in regards to when the timing of transplant has always been discussed, whether to do a sleeve, whether to do a ROO, when to do those surgeries. But when you look at the effects of bariatric surgery on absorption of immunosuppressive medications, we know that a ROO and Y will cause a lot more malabsorptive problems. So we tend to avoid that if we can, and the sleeve tends not to do that. We studied this in 24 patients who received this type of drug after a sleeve gastrectomy, tested all their levels. What we found in the time concentration curves that there's no difference in tochrolimus reabsorption, even by genotype. And then also, we thought maybe there would be in cell sept, but there wasn't. The immunosuppressive levels, though, in the patients who had a sleeve gastrectomy post-liver transplant, it was very important for us to monitor the immunosuppression levels very closely because they did tend to change quite a bit after their sleeve because the dosing changes because you cannot give them their pills. So that caused this variation. So I'll just quickly go into that. So for pre-liver transplant, we talked about our MELD score less than 15, no evidence of decomposition, no ascites, and platelet counts greater than 50. At our institution, we have not instituted a simultaneous yet, but I do think it should be part of the armamentarium. If you have a MELD too high or the risk is too high for pre-liver transplant bariatric surgery, if they failed medical weight loss therapy, and as long as their hemodynamic is stable during their liver transplant, I think that you should go ahead in this patient population and do a sleeve at the time of liver. And for post-liver, we should be identifying patients early who show signs of potential recurrent NASH and getting them through this process the sooner the better. Don't let them turn to that patient who is seven years out who looked like we just kept on biopsying and biopsying and biopsying. I mean, I don't know what we expect to happen. As the biopsies are continuing to get worse after five years, do we think at seven years they're going to get better? No. I mean, the real key to this is to treat it early, and so that means we need to have definitive therapy. So in conclusion, a multidisciplinary approach, and I cannot stress this enough, is truly what's required to really treat this issue of fatty liver disease NASH and post-liver transplant recurrent NASH. Sleeve gastrectomy has been shown now in multiple different ways to be safe and effective in treatment of not only NASH, whether it be before transplant, recurrent NASH, but also for diabetes after transplant. But we need to have proper patient selection, and we have to be very, very careful, especially in the pre-liver transplant group, because we can really hurt patients by doing something like this and trying to help them. But what we really need is to get some kind of study so that we can look at and figure out what the true best timing of bariatric surgery is. But an approach that involves pre, simultaneous, and delayed is probably going to be the best. These are two of my kids, not the west face of K2. This is climbing in Maine, but still very tough, right? All right. Thanks, Ty.

obesity

liver transplant patients

bariatric surgery

sleeve gastrectomy

patient outcomes