I'm tasked to give the Liver Transplantation for National Obese Patients and Surgical Considerations talk. I have no disclosures. I think you'll see a lot of similar slides this afternoon. It's no news to this group that obesity is an epidemic. Worldwide, the obesity has tripled since 1975. WHO in 2016 considered 650 million people around the world as obese, which constitutes about 13% of the whole world population. You can see North America, including the U.S. and Mexico, have one of the highest incidences in the world. If your practice is like ours, I'm sure you have a lot of these big-boned people in your practice. Because we have increased intake of energy-dense foods and increased physical inactivity compared to our ancestors even two or three generations ago, we weren't living the same way that we are living right now. Because of this, we are seeing NASH and obesity as an indication for listing for liver transplantation go up tremendously. Compared to 2004, in 2014, we've had about 170% increase in NASH as an indication for listing for liver transplantation. Not only that, but the overall numbers of liver transplants done for an indication of NASH and obesity is going up as well. This is, along with the alcoholic liver disease, two more common reasons for transplantation, especially as we treat hepatitis C and the reason for liver transplantation in hepatitis C patients are going down. This segues into what kind of problems we get into liver transplantation when we do transplantation for NASH and obese patients. We know that NAFLD and NASH, even in the non-cirrhotic stage, is an increased risk for hepatocellular carcinoma. In the United States, NAFLD accounts for 59% of all HCC cases. And in England, there's been a tenfold increase in HCC associated with NAFLD within about 30 years, accounting for now about 35% of all the cases done in the UK. And as I stated, the HCC may also occur in absence of cirrhosis in patients with NAFLD due to the pathophysiology of the fatty liver disease. If you look at the HCC, you see that the report from the Global Non-Alcoholic Hepatitis Council came recently that the HCC prevalence among the patients with NASH is increasing at the fastest rate and much faster than the similar rates for other diseases. And from 2002 to 2016, there's been a 12-fold increase in the HCC prevalence in patients with NASH. Not only that, but you realize that the male men have an increased risk for development of HCC. Those with advanced age have even increased risk, and those with diabetes have a much higher risk than those without diabetes in the NASH population for HCC. These are the overall SRTR data in 2017. What you realize here is that these days, about half of our patients that we transplant have BMIs over 30, and some have even over 35 and over 40. So the trends are increasing. The most common cause of death for patients with NAFLD continues to be cardiovascular events, as most of these patients have accompanying metabolic syndrome. Patients who undergo liver transplant for NASH may be at an increased risk for perioperative cardiac events, so those need to be screened very carefully. And even in patients who are obese, there's this fact called sarcopenic obesity. So sarcopenia is also associated with worse outcomes, although they might have an increased BMI compared to your other patients. Surgical issues are obvious to most of us, from the time we put these patients on the table, thinking about whether we can fit them on the table, to the availability of the retractors that were designed 30 years ago, when the incidence was much lower, to the dissection, to the tissues you have to go through, to the anastomotic complications, all those things, as you might imagine. The impact of obesity has been studied extensively. The initial results, looking at the SRTR data from 1987 and 2007, showed us that the outcomes were worse in higher BMI patients compared to normal BMI patients. But in a more recent analysis of the same SRTR data, spanning 2004 and 2011, we are finding that there may not be any difference in outcomes, which might be a reflection of how we are selecting patients better these days. Although it is hard to confirm this, because SRTR does not have the granular data that this kind of analysis requires. If you look at long-term outcomes for NASH, it is clear that these patients do not do as well as patients who are transplanted for choastatic diseases or alcohol-related cirrhosis. So there is clearly an inferior outcome over the long-term, if you look at the 10-year survival. And most of this is related to what I alluded to before, because of cardiovascular events related to the metabolic syndrome these patients have. This is Kim Watt's data from about 10 years ago. Long-term risk factors continue to be related to age, the presence of diabetes, and renal insufficiency, all of which are in high prevalence in our patients with higher BMI and NASH patients. Several single-center studies looked at the long-term outcomes with obesity. This is an Australian liver transplant cohort looking at about 617 patients. What they found was patients with obesity and diabetes had worse 5-year outcomes compared to patients with either just obesity or just diabetes alone. So the two factors had a cumulative effect and worsened the outcomes in 5 years. And not only that, we know that when we transplant these people, we are all doing it. We are having to face challenges of outcomes with prolonged ICU stays, with more resource utilization and overall more expensive. We just have to accept the fact that these patients will remain in the hospital for a prolonged time. They might have more readmissions so they are overall more expensive liver transplants. Moving on to the impact of weight loss on fibrosis, this is a well done study that was published several years ago and set the stage for what weight loss can do for fibrosis in 45 patients with serial biopsies every 5 years. This study confirmed that patients who achieved at least 10% weight loss could have their fibrosis score lowered and was predictive of fibrosis regression. Those patients who lost less than 10% of their total body weight did not have any change in their fibrosis score and obviously those patients who had weight gains had worsening fibrosis scores. The bariatric surgery, which outside the cirrhosis world is well established with very nice effective long-term weight loss, this is the New England Journal paper from over 12 years ago now looking at vertical banded gastroplasty and gastric bypass, all of which can sustain weight loss for a prolonged period of time compared to control groups which do not have a weight loss, prolonged weight loss. Not only that, but patients who had sustained weight loss because of the bariatric surgery had 95% reduction in new onset diabetes at 12 years and 51% resolution of diabetes type 2 at 12 years. So this is clearly a well established metabolically advantageous procedure in patients who do not have cirrhosis. I think later this afternoon Dr. Tai Duan is going to go into detail about the bariatric surgery so I'm not going to spend more time, but the most common things that we do these days in the restrictive procedures are the gastric sleeve which provides a slower weight loss, lower rate of complications which is durable, and the most common restrictive plus malabsorptive procedure we do is the Roux-en-Y gastric bypass which to date is the most durable, standard, and effective in long-term weight loss and this is a picture depicting what we do. Again, the sleeve gastrectomy on the right side, upper right side, and the Roux-en-Y gastric bypass in the lower left side, just the anatomy. Bariatric surgery in cirrhotic patients before they need a liver transplant have been tried by many centers. Overall, longer OR times, higher complications, and it can be only done in compensated child's age cirrhosis patients. It is too risky to do it in child's B and C patients, clearly. If you look at the overall nationwide inpatient sample from the U.S. from 1998 and 2007, you see that when this procedure is done in cirrhotics it comes with a lot of complications both morbidity and mortality. In hospital mortality of these patients upwards of 16% compared to 3 in 1,000 patients with no cirrhosis and overall the length of stay is much higher in those patients, no doubt. Before transplant, it's not an option. It could be done after transplant or it could be done concurrently with transplantation to provide a more sustainable weight loss. Liver transplantation after bariatric surgery has been reported. This is a report by Sauer 1 and 0 which had 11 patients, 9 of which underwent a Rheumatoid Gastric Bypass, one had a sleeve, one had a Diginal Allele Bypass, the mean length of stay was 10 days, mean operating time was 405 minutes, and they found that the post-op survival was similar to those who had no bariatric surgery. This is another report in which lap gastric sleeve was used for patients who had a liver transplant already and the results were reported only up to 6 months with good excess body weight loss ratio in these patients. This is yet another report, again, Rheumatoid Gastric Bypass. The story is similar. It could be done, it could be done, but it should be done only in selected patients. This is what we do. This is the initiative of my partner, Dr. Julie Heimbach, Mayo Clinic, who gets all the credit for this. This is bariatric surgery during liver transplantation. It is a good option for selected patients who have not attained goal weight and have high MALS scores, so not undergo elective bariatric surgery prior to liver transplant. What we do is we do a gastric sleeve resection combined with liver transplant. It does not have any malabsorptive function, but it provides a slower and sustainable weight loss operation. These are the first results we published several years ago, at which point we had done only 7 patients with simultaneous bariatric surgery and the results were good, which was encouraging, so we continued to do this. This is what the operative field looks like after you do the liver transplant. The liver is reperfused. Once the area, once the bleeding is stopped, then we proceed with an open sleeve gastrectomy procedure. These are the more recent results, in which we reported 29 patients who underwent a combined liver transplant and sleeve gastrectomy. In this, 17 of these patients had more than 3 years follow-up, and the comparison was to 36 patients who were obese, but underwent just liver transplantation. The total body weight loss at the operative 3-year point was about 34% in those patients who had the simultaneous procedure, compared to only about 4% in patients who underwent liver transplantation. Again, this is the weight loss that patients achieve prior to liver transplant usually is not sustainable unless they have a sleeve gastrectomy at the time of the liver transplantation. This is the 2-year BMI data. Most patients who have lost weight to achieve the goal unfortunately put back their weight after the liver transplantation and get back to their BMI of 40, which they start with, whereas the combined sleeve gastrectomy patients have a sustainable reduction in their BMI. Not only that, but we have shown that the insulin resistance index goes down tremendously in patients who have the sleeve gastrectomy after liver transplantation at 2-year follow-up period. So this is what we do at pre-transplant. Any patient who comes to our transplant center with BMIs over 40 and NASH cirrhosis meets with a transplant dietician as part of a protocolized approach. They are given calorie goals, which is 1,200 to 1,400 per day for women and 1,400 to 1,600 per day for men. They are given exercise goals, daily weigh-ins and logs and frequent follow-ups. And if they do not lose weight and they continue to be above BMI of 40, they undergo a bariatric surgery education. Those that have the combined procedure have a sleeve gastrectomy diet, which is protocolized, and they are evaluated every 3 months post-transplantation for the first year and then annually thereafter by the team that includes the transplant surgeons, hepatologists, but as well as the bariatric surgery group. This is now being accepted more and more, and both European and Israeli centers have reported their outcomes recently, and this operation could be done anywhere else with a protocolized approach. So in summary, it is clear to all of us here that obesity is an increasing epidemic worldwide. Potential liver transplant recipients and donors are no exception. We are seeing more and more obese patients that are coming through our doors. Obesity impacts long-term survival after liver transplant negatively, so whatever we can do to achieve better outcomes should be tried. The pre-transplant options are bariatric surgery, but it could only be done in selective patients with relatively compensated liver disease, and post-transplant options exist, but probably requires more resources, whereas the Combined Liver Transplant in the San Diego District appears to provide good results at least with the last 5-year data that we have. So I'll end there. Thank you. Thank you, Temuchin. That was excellent. We're going to get to questions when we do our case reviews here at the end, so that's great. Thank you, Temuchin.

obesity

liver transplantation

Non-Alcoholic Steatohepatitis

NASH

bariatric surgery