Um, and I've been taxed with, um, rebuttaling this question, and he very eloquently and beautifully talked about completely irrelevant to the question data, I would like to point out. So, that's because there's literally no data to talk about, except for the stuff he just reviewed. So, I'm just telling you that it does not matter, I have some unrelevant disclosures except for this one. And this is because I've basically set my whole goal to try to convince the community that actually recurrent NAFLD and NASH is important, and that we do need to pay attention to it. And now I have to basically convince you that that's not the case, which is actually very easy to do because the data supports that, and it's really just my opinion that would support Dr. Hennouiné. So, I will now begin to defile myself. So, does it matter? Actually depends on what the last part of that question is. What are we asking if it matters? So, does it matter for patient and graft survival? Are we asking for, does it matter for morbidity, cardiovascular events, malignancies that he talked about in the general population, and in transplant, for our own psychiatric health, for us trying to make decisions? We have a lot of biases that go into our decision making on who we're going to transplant. We have a lot of data that goes into that as well, and we try to do our best in offering organs to people that we think are going to have a good outcome after transplant. We don't want to lose those organs, and we certainly don't want to lose it to recurrent disease if we can prevent it. And we know that this does recur. He's demonstrated some of the data out there. If you compile all of the studies that have been looking at, does recurrent NAFLD, such as fatty infiltration, happen? Heck yeah, it happens all the time. Pretty much anyone transplanted for NASH is going to probably get steatosis in their liver. A smaller percentage, maybe about somewhere, anywhere, 7, 70%, totally depends on the studies. Totally depends on are you doing biopsies, are you just basing it on ultrasound? The studies are all over the place. Most of them are pretty low quality, including mine. Cirrhosis has been demonstrated in maybe 5 or 10% of patients at 5 or 10 years, but the actual graft loss related to cirrhotic stage allograft disease is really not well identified. Yes, some people do go forward to needing retransplant, but many of those, when you look at the study that was actually done on retransplant for NASH, were actually for other reasons than recurrent disease. So it's the hepatic artery thrombosis, primary non-functions, et cetera. So he's already shown you this study, which basically was just looking at de novo allograft steatosis and recurrent allograft steatosis, and you've already seen that there's really no difference in survival. There really is no difference in cardiovascular outcomes if you have steatosis in your liver. What is different is if you had underlying NASH, which we are not actually correcting the underlying disease process that these people have had. We're just swapping out the liver, really. And in fact, the NASH patient in this particular study had higher rates of survival. Most of the studies that you'll see in the current era have had equal rates of survival after transplant compared to other common causes of chronic liver disease. So a lot of this depends on what's our point of even asking the question. Are we looking at trying to prevent long-term outcome problems? Well, it's not really a matter of the allograft recurrent disease that is causing all of these mortality issues that he's even reviewed himself. So cancer, infection, cardiovascular disease are in these patients that are going to have those issues, whether they have allograft steatosis, allograft NASH, or not because they're potentially related to the underlying disease that brought them to transplant. There are some outcomes that, again, were no different when we looked at it in detail. So patients that had actual NASH on a biopsy proven, these were not protocol-based biopsies, so it's completely flawed data. There was no real difference in cardiovascular events. There was no difference in death, and there was no significant fibrosis progression that we saw in this small number of patients in our study at Mayo. But if they did have allograft steatosis, not a small percentage of patients are going to end up with a cardiovascular event, and that is what subsequently is leading to their demise and not the recurrent disease itself so far. So we've already talked about whether cardiovascular events, whether our outcome that we're looking at is other morbidities. It was not, again, the steatosis and the allograft that was the predictor or association with cardiovascular events. It's the underlying NASH, which is the 30 years of diabetes and or smoking and or hypertension or hyperlipidemia that these patients have had, and the allograft steatosis and steatohepatitis is not necessarily the reason. So if our bias really is, is are we asking this question because we want to avoid transplanting these patients or we're worried about they're going to gain weight, they're going to go back to eating, we haven't treated their addiction, we try to treat the alcohol addictions, and that whole cadre of questions is another loaded gun as far as debates go. But if we look at alcohol recidivism, we have some recidivism rates of 10 to 42%. We know that survival, if there is recidivism, is less in our transplant patients, yet we continue to transplant alcohol-related liver disease. We continue to transplant hepatitis C despite absolutely knowing that there was worse graft outcome and patient outcomes on recurrent disease. So we don't have that data to say that, and we can't do that in NASH yet without any kind of concrete data. So we do worry about the weight gain post-transplant. We do worry about not having treated their addiction, but does that mean we don't transplant them? I don't think that that's really what we're looking for here. So we know that people are more obese. We know that there's more metabolic syndrome coming into transplant. None of this is a surprise. None of these particular issues are really reasons not to transplant patients. Survival based on obesity is pretty much the same. Graft survival is pretty close to the same, and we're just seeing it more commonly. So if back in 1991, even though they were completely dead wrong, and I just love quoting this paper, it's not particularly relevant, but at one point we thought hepatitis C wasn't going to be a problem in our allografts, and we were dead wrong by we, I mean, those authors. And I do actually think that, personally, I think that we don't know enough, and I do think this is actually going to happen, but does the data support that right now? Absolutely, it does not. We still went ahead and transplanted patients for hepatitis C. So we don't know anything about this, so we can't not transplant patients out of concern for recurrent disease. So I don't think, based on what we have out there right now, data on recurrent NASH outcomes is pretty limited, pretty small studies. We definitely need more data in this particular field, and we are going to get more data. So Mary Rinella and I and several other colleagues across the country, we've got nine centers, we've created a consortium, we're looking at all NASH patients retrospectively right now in all of our centers, and we've got a prospective study going forward. So we're going to get these answers, and so over the next coming years, if we could have this debate again, then we'll actually have some data that we can present. So no, I don't think NASH recurrence is currently, based on evidence-based data, a problem, but my underlying feelings are here, and we're just waiting for the horde. Great. Thank you. Thanks, Kim. Abraham.

non-alcoholic fatty liver disease

NAFLD

non-alcoholic steatohepatitis

NASH

liver transplant recipients