Hello. Welcome to Session 2 of the Surgery and Liver Transplantation Workshop on Living Donor and Split Liver Transplantation. My name is Bijan Ektesad with Cleveland Clinic and moderating this session. We have four excellent presentations by four experts in the field. Dr. Heimbach from Mayo Clinic will present liver transplantation from living donors. How far can we push the envelope with respect to size and age? Dr. Reyes with University of Washington will talk about split liver transplantation, right, left, lobe split. Should we push for it? Dr. Hashimoto with Cleveland Clinic will talk about portal inflow modification in liver transplantation and split livers. Can we make it safer? And Dr. University of California, San Francisco will talk about possible allocation policies to promote split liver transplantation. At the end of this session, if we have time, we might be able to entertain some questions. Enjoy the talks. Hello, I'm Dr. Julie Heimbach, Professor of Surgery and the Director of the Transplant Center at Mayo Clinic in Rochester, Minnesota. And today I am delighted to talk to you about liver transplant from living donors. How far can we push the envelope? I have nothing to disclose. So the whole topic of liver transplant really always has to be considered in the context of the waiting list. If we didn't have a waiting list, really most of the controversy and concern about transplant would dissolve away. But unfortunately, we have 106,000 patients currently listed in a waiting liver transplant. Of these, almost 12,000 are waiting for a liver transplant. And for context, last year in 2020, we were able to do almost our highest number ever at 8,906 transplants. But still, that doesn't meet the need of that number of patients that continue to wait. And for those patients who are waiting, what actually happens? So this is from the SRTR annual report. And what we can see is that when patients are followed over three years, about 55% of them undergo a deceased donor transplant. And in the pink down here, a small cohort undergo a living donor transplant. Unfortunately, we also have a cohort that either dies on the list or an even larger cohort who is removed from the list, which typically is because they are too sick to undergo a transplant. There is also a group, as you can see in blue, ever decreasing that continues to wait even out as long as three years after being listed. What we do know about living donor liver transplant is it is associated with superior survival. And this is established from the eight adult to adult liver transplant cohort published in 2007, showing from the day that the patient comes for their evaluation, if they have a suitable living donor that is also able to be evaluated, and they're able to undergo a living donor liver transplant, they have a lower probability of death than compared to those who are wait listed, or who have a deceased donor transplant. So this clearly does establish the survival benefit when measured from the day of the evaluation, with liver, living donor liver transplant having the superior outcome. Other advantages of living donor besides the opportunity of improved survival opportunity for timely transplant, which avoids disease progression, most notably, that morbidity on the wait list, you also get a healthy donor liver with a short preservation time. The disadvantages, however, of course, very well known that this is your family member or your close friend who is now having a surgery that they don't need it puts them at risk of morbidity, including approximately 30% chance of, of complications, as well as the risk of severe complication, including death, or need of transplant, which is point three, also the possibility in every case of living donation, or coercion, and we have a higher rate of recipient complications, most notably, ciliary complications. So pushing the envelope, this is particularly amazing to think about how we may make things better for the donor. And this is from Sam seen really groundbreaking work on his report where you can actually achieve this kind of outcome in your donor who has a fully laparoscopic approach with the left hepatectomy being reported in this series. And in this series, from Korea, looking at a total laparoscopic right hepatectomy compared to the open and showing actually very similar outcomes in these two groups, but obviously, with the patient, hopefully in the long term, having an easier time of their recovery. And so looking at transplants by donor type, the vast majority of patients still undergoing and actually more recently, much higher numbers of deceased donor transplant due to the increased availability of deceased donors, which has a variety of different reasons behind that. But we actually have also seen, it's not perceptible in this graph, but this 524 living donor liver transplants in the United States in 2019, actually tied this other previous high, right after we started doing living donor liver transplant, dropped only very slightly in 2020. So you can see this is on the rise. And this is even more evident when we look at pediatric transplants by donor type where, you know, a high number of these patients almost 100 happened for pediatric recipients. And in fact, not the concurrent rise in deceased donor pediatric transplants that we see for adults. So this highlights, this is again, the SRTR report, something that I think is quite new and interesting. And this concept of increased numbers of directed donors and increased numbers of other as opposed to this number of related donors, which is also going up. And that whereas the spouse donation, or distantly related donation has been really steady. We also see for the first time, a slight increase in parent donations. So these novel relationships are now being seen. And this is report from Toronto, showing 50 patients who are basically were anonymous, meaning that they did not have a connection to their intended recipient. Sometimes they were directing it to a specific waitlisted candidate that they identified through either social or public media. And sometimes it was non directed. And these were reported over a series of 2005 to 2017, median age of 35. Their primary motivation being to save a life or to help others were listed. And they reported that the things that made it most possible were the supports that they had, that are somewhat unique to Canada with our social, legal, financial and healthcare support, all identified as facilitators from the perspective of the donor. They did have complications, but not any more than would be typically seen in their non anonymous population. And this shows us non directed and directed donation. This is a 57 patients from the Pittsburgh report 2010 to 2019, 37 directed and 22 non directed. And in this, they had again, a median age of 35. And then they also performed a matching between a subset of these 21 of the non directed donors matched to 21 emotionally related donors. And in these cohorts, they really saw no differences in the post op recovery. And this they also looked at the motivation for these folks and what they found for the non directed donors. They were 79% of them actually are motivated by family members with a similar illness. Those that were anonymous directed donors saw the individual in media or they even cited religion as their reason that they came forward. So what about pushing the envelope related to age, we just talked about pushing the envelope related to relationship. And this you can just see the US experience where we're really not making any differences. The vast majority of our donors are between 40 and 54 or between 30 and 39. With very few being less than 18. And a steady number being 55 and over. So we're not really looking at the geriatric donors here in the United States. But there are some reports about using donors over age 60. This is a single center report from Japan, 23 patients now of course, understand that these are Japanese individuals who may be different than individuals in other countries, compared to 411, who are under 60. And they really saw no differences for the donor and their recovery, no differences for the donor and their complication. And importantly, no differences for the recipient. Although in this time of the publication, which was 2006, they were looking at one year post transplant survival of 73% for their older donors and 77% for their non older donors. So these are clearly very different from the survival outcomes that we see in the current era. What about BMI? And so this again, shows us the current US experience from 2008 to 2020. And interestingly, in the green are the donors with a BMI 30 to 35. And we do see we're starting to see a rise where 20% of donors done in 2019, had a BMI between 30 and 35. So that's pretty remarkable. And we can see a decrease in what is actually a normal BMI, which is 18 to 25. And a pretty steady amount between 25 and 30, which is the highest. So again, overweight being the most common type of donor being done in the United States. So I think really, it speaks to the current epidemic of obesity and the fact that really everyone's pushing the envelope in this regard. There are publications that support this. So this is a donor BMI greater than 30. Again, from the Toronto group 105 donors with a BMI greater than 30 limited to those with less than 10% steatosis. So nobody with more than 10% steatosis would be a donor. They had similar complication rates, similar graft survival in those two cohorts. Their hernia and wound infection were the same and recipient outcome was identical. This is actually a systematic review of donor weight loss interventions. And they were able to conclude when they looked at these six different reports about donor weight loss that actually that this is feasible and safe. And they were able to show that there was effective at the weight loss. Again, there's a publication bias because people don't usually write about what doesn't work. But in the published series, it was effective for the donor and with good recipient outcomes. And this is a paper from Turkey on 900 patients. And they did look at these sort of comparison risk factors with their donors over age 60 having a higher complication rate than their other patients. It was not statistically different, however. And then they had some patients with a BMI greater than 35 actually, 12 and two of them experienced a complication compared to those between 30 and 35 where they had 20% complication rate. So again, suggesting at least in this cohort that these risk factors could still result in a suitable outcome. What about the type of living donor graft? In the United States, you can see actually this has been pretty steady, not a lot of change. And in fact, if anything, a rise towards the right lobe in the more recent era, which is interesting, especially in light of the discussion about the left lobe potentially offering a greater benefit for the donors. This is looking at outcomes when we are thinking about smaller grafts. So graft to body weight ratio less than 0.8, single center analysis from Toronto, really showing no difference in the complications either for the donor or for the recipient in terms of graft and patient survival. What about for even smaller grafts? The graft to body weight ratio less than 0.6. So this is a single center Japanese analysis from 2006 to 2019 with a clear demonstration with early graft loss and in fact, patient death in this cohort when the graft to recipient weight ratio was less than 0.6. The patients with between 0.6 and 0.8, essentially the same as those greater than 0.8. And the risk was increased when they had avion compatibility and when the donor was greater than age 50. More recently, Hong Kong has published their experience and this came out in 2021 in Annals of Surgery from 2001 to 2017, group one showing here where they had a graft to recipient body weight ratio of less than 0.8 on the imaging and then on the actual final, less than 0.6. And then compared to, I'm sorry, this is less than 0.6 to 0.8 or greater than 0.6 to 0.8. And this shows less than 0.6, 39 patients less than 0.6 make up group one, group two is between 0.6 and 0.8, group three is greater than 0.8. And actually what they were able to demonstrate is equivalent outcomes. As you can see here on this Kaplan-Meier group one, that's less than 0.6 showing actually not statistically different, but numerically improved survival post-transplant. They account for this by meticulous recipient, donor matching, so selecting the proper recipient, meticulous technique, accurate measurements of the graft weight prior to transplant and portal inflow modulation to keep that portal inflow less than 20 with selective spondylic artery ligation. There is a systematic review of this actually does show that low graft weight is associated with inferior three-year, one-year and then three-year survival. This is showing also small for size being worse. Importantly, long-term quality of life analysis has been done. And what that shows for us is that in this group, which is 374 patients from age to all, looking at the physical and mental component scores after transplant, this is worse when the recipient dies within two years. So the recipient survival does definitely have an impact on the donor. So I think this is an important consideration when we're pushing the envelope, we want to make sure that we have outcomes that are acceptable for the donor. But to stress, living donor liver transplant, key takeaways, this is an increasingly important option in the area era of severe organ shortage. It's a major operation for the donor with potential for serious complications. Laparoscopic cystic and fully lap hepatectomy is being performed. Success for well-selected smaller grafts in heavier donors and older donors and interestingly non-directed anonymous donors are now being reported. Thank you very much for your attention. Hello, I would like to speak with you today about split liver transplants and the path to push for more. I have no disclosures. The question about pushing for more has to be preambled by the quality of the liver grafts in split transplantation as we know today. And the question about possibly unfairly disadvantaging larger candidates and also what the impact of different liver allocation policies have on the impact of increased utilization of split liver transplants. Are splits an inferior type of graft? This concern has come up given the paucity, so to speak, or even the decreased numbers of split liver transplants performed in the last 10 years. And we were interested in seeing what the survivals were and what the factors of impacting survival of these grafts were. So we looked at UNOS data from 2002 to 2016 and demonstrated the risk factors for failure, which were donor age less than 11 or greater than 30, the same program doing both grafts, increasing cold ischemia times generally greater than six hours, and inadequate size of the graft by body surface area of donor recipient and program experience of less than 23 cases. Factors that were not significant in survival were the donor gender, cause of death, race, or age, as well as vasopressin support, elevated transaminases greater than three times normal, splitting in situ versus on the bench, sharing between two programs of these grafts and donor BMI. These were not significant factors. So consequently, optimum utilization and survival really hinges on donor age between 11 and 30, encouraging the participation of two transplant programs, efficiencies in time to decrease the cold ischemia time maintained at under six hours, inadequate size matching by donor recipient body surface area. Training and regulations of allocation also have a very important factor, as we will see in a little bit. It is difficult to get good data from UNOS in terms of right and left splits, but here we, based on registrations, we have the number of grafts split left, split left lateral, split right, and split right triseg over the course of 19 years. And notable is 413 split grafts actually did not have a matching leftover segment to be transplanted. And that could be, could have been due to local factors or inability to place the graft. But also notable is the increasing demonstration of utilization of the right lobe, both as a triseg and as a right lobe. So from that standpoint, all the variations are presently in practice. Survival by type of graft, you can see that the split right triseg has good survival as well as the left lateral segment. The worst survival is with the split left whole graft. And these are comparing it to whole liver transplantation in the purple line. So their survival is actually pretty good. And grafts, that was over 14 years of follow-up and the graft survival at three years shows, similarly shows the worst survival with the whole left graft. The other grafts actually have pretty good survival when compared to whole liver grafts. The survival of the left side is worse in adults than in children, as can be seen here. And interestingly, the, when looking at it from the size standpoint, the graft loss increases when the donor to recipient body surface area is less than 1.2. And as you can see here, three quarters of the adult split grafts when using the left side were actually small, considered small when looking at it from donor recipient ratios. In the child, the increased loss is by when the donor recipient ratio is less than 2.3. And most grafts actually were greater than that ratio. Consequently, the better survival in the pediatric utilization of the left lateral segment right and right try saying the, the determining donor recipient ratio was 0.9 and as you can see here, most transplants were actually above that, demonstrating the, the better survival of, of the right side in the adult population. And then here with the left lateral segment. There was no point of increase graph loss, given its use predominantly in the babies so from the standpoint of size and adequacy of size. They were pretty good. If we actually match good size left sided graphs to appropriate recipients by the donor by optimum donor to recipient body ratio, we can see that the survival of the left side is significantly improved. So, sizing is an important factor according to this study are split transplants and impure type of transplant No, they compare well with the whole graph, and the experience in the centers that are that have been performing them as noted by the UNOS data is actually very good. When we look at potentially split up potential splittable livers during this period of record. We have 8294 graphs, based on the, on the factors noted in our study, or 23% of graphs that could be split, potentially, with more split graphs hinder the larger those candidates. Here's a graph showing what where where most donors lay in terms of body surface area 1.9 infants, adolescents, and women and male recipients. When we look at the dividing donors and recipients into quartiles and the availability of craft offers. You can see that the smaller recipients have a less of a chance of receiving a donor offer. Then the mid size recipients. About 15 to 70% decrease probability of a donor organ being available. It would seem that the bigger recipients would have a similar difficulty but interestingly in practice, those recipients actually have a lot more offers and tolerate the smaller graphs, as long as the body surface area ratios are acceptable. Split donor livers to equalize probabilities of transplant is is possible, as you can see here if we using this large group of splittable livers, then transplanting them into the using the new criteria into those cart into the lower regimen quartile of the smallest that recipients, we would be able to address this modeling that shows here that presently. There's a 2.4% disadvantage to small stature recipients, mainly women, and then using the model to optimize allocation by donor recipient ratio. can be addressed by utilizing 0.5% of the entire donor population or 2.3% of the new donor criteria, the, the mortality weighting of the pediatric population can be addressed if these livers are split routinely. With more split livers and fairly hinder larger adult candidates. No, they would not because they have plenty of livers available and actually we would be able to transplant small statured adults as well as children. And it would be a fair allocation system. Regarding the allocation system. How does it, how does splits do with that here, you can see in the area of coven in the lighter blue color donors were actually increased in the United States. There were more donors. Yet with the allocation policy even though there was a slight increase in splittable livers from 2017 through now. The actual number split livers perform decrease dramatically. So far, there's two variances open at this time in the United States for splitting liver the open variance, which may offer the remaining left or left lateral segment into a different eligible potential recipient registered at the same transplant hospital or affiliated pediatric transplant program gives you plenty of flexibility, and the close variance where the leftover segment is offered according to the standard allocation regimen to appropriately male appropriate melt by rank. In the US the liberal allocation policy is. It is relatively early, whether to determine whether there is a truly negative effect of this allocation policy but so far there does seem to be less split livers available. Should we push for more splits, yes the graphs are working well. There is good survival when compared to whole graphs. It would alleviate allocation disparities by size for sure the small statured adult as well as children. And the, it is notable that we likely may need allocation rules to address this type of practice in the United States in order to optimize these splitting of liver graphs. This is done in the UK and in Italy by national mandatory splitting of livers. And, as noted here. It's a must do. If liver, technically, and by quality wise is splittable. But most importantly each center noted here you center will maintain a list of surgeons deemed capable of splitting a liver and this is critically important in Italy, such a policy as well has increased the number of split livers from six to 8.4%. So it would seem that splittable liver. In order to push for more, we would have to urge or mandatory split the appropriate graphs particularly in an area where allocation policies may change or be edited so to speak, according to the growing experience with fairness of distribution of livers but if we want to achieve that goal of more splits. This may be necessary as far as mentors splitting of appropriate graphs, and also mandatory training requirements in in our transplant programs I think the living donor transplantation is a great environment to teach splitting of livers. And I think that taken taken with the actual splitting of the organ can give the trainee the appropriate experience to then go on and expand on their experience. Certainly, this is something that is necessary and centers that are practicing routinely pediatric transplantation. Thank you very much for your attention, and I am open for questions. Thank you for the kind invitation for this nice meeting. My topic today is portraying for modification in living donor liver transplantation and split liver transplantation. My name is Koji Hashimoto. I'm a transplant surgeon at Cleveland Clinic. I'm the director of living donor liver transplantation and pediatric liver transplantation. I have no disclosure. The partial liver grafts are known to help increase the donor pool for transplantation. Partial liver grafts are underutilized in the United States with many reasons. One of the important reasons is the use of small partial liver grafts may increase a risk of graft failure due to graft recipient size mismatch, so-called small foci syndrome. Importantly, hemodynamics such as inflow and outflow of partial grafts is very different from the whole liver grafts. And actually, this is a key player to determine the graft outcomes. This slide shows the main graft types in partial liver transplantation. In this presentation, I will be talking about mainly the hemily back grafts for adult transplantation, such as the left lobe and the right lobe. The small foci syndrome is a clinical syndrome characterized by persistent jaundice and coagulopathy, ascites, mental status change, and eventually the recipient developed renal failure and sepsis. It is very important to rule out any surgical complications in the graft failure. The pathophysiology of small foci syndrome is not fully understood. In 1996, the small foci syndrome was first described by Dr. Johnny Mott. In his study, the small foci syndrome was described as a functional impairment associated with paradoxical histological change, typical of ischemia. So why does small foci syndrome develop ischemic change, even the living donor graft has short ischemia time? In 10 years from this study, the Pittsburgh group gave us an answer. When the small graft is transplanted into a recipient with severe portal hypertension, this small graft has the hepatic artery spasm due to hepatic artery buffer response. Also, the excessive portal rate flow into the graft mechanically destroys the liver parenchyma. This slide shows the difference in the portal flow volume between the living donor partial graft and the deceased donor whole graft. As you can see, the living donor portal flow is much, much higher than the deceased donor graft. So if you merge the two histograms together, you can clearly see the difference in the portal flow. Once the small foci syndrome occurs, there is no treatment for it, and the short-term and long-term outcome is detrimental. So the best treatment for small foci syndrome is to prevent it from occurring. It is very important to understand the risk factors for small foci syndrome to prevent it. There are five major risk factors, such as small actual graft size, suboptimal graft quality, recipient disease severity, excessive portal flow, and suboptimal venous outflow. Now, I want to introduce you to the concept of functional graft size using these five risk factors. Please imagine that the area of the pentagon is minimal functional graft size to prevent small foci syndrome. The functional graft size is determined by actual graft size, graft quality, recipient disease severity, graft portal inflow, and outflow. Let's think about this case. We have a healthy living donor, 24 years old, who is donating the right row with a graft-to-recipient value at a ratio of 1.2%. Biopsy shows no steatosis. The right row graft has a large dominant right pelvic vein, and segment 5 and 8 veins will be reconstructed on the back table. The recipient is 55 years old, alcoholic cirrhosis, HCC within melan. Childhood score is A, and the merit is only 9. So, this case has a large graft, excellent graft quality, low merit score, minimal portal hypertension, and excellent venous outflow. So, the functional graft size of this case is much bigger than the minimum requirement to prevent small foci syndrome. What if this case has suboptimal venous outflow? The graft gets venous congestion, and secondary, the portal pressure increases, and the functional graft size of this case becomes much smaller. What about this case? We have a deceased donor, 25 years old, brain dead. This is a fairly large donor, 80 kilogram and 185 centimeter. We received left row graft, which was 650 gram. Biopsy shows no steatosis. The liver enzyme was mildly elevated. The recipient was 49 years old, female, PBC. This was a small recipient of 50 kilogram. Merit was 32. There was a situs, and ischemic time was eight hours for splitting on the back table. This case has a large graft, even the left row graft. The graft quality is not as good as a living donor because of the long ischemia time and elevated liver function testing the donor. High merit score. The graft inflow is acceptable because we received a fairly large graft. That can compensate the portal hypertension. The venous outflow is excellent. The functional graft size of this case seems to be larger than the minimum requirement. In a split liver transplantation, it is very important to have a large donor and small recipient. This combination makes the graft recipient body weight ratio is high so that you can compensate high merit score and suboptimal graft quality. In general, it is important to keep the graft recipient body weight ratio greater than 1% in the split liver transplantation. What about this case? The living donor is a 51-year-old female, BMI 34, donating the left row with graft recipient body weight ratio 0.75%. The recipient is a 61-year-old, NASH cirrhosis, severe portal hypertension. Merit was 23. This case has a smaller graft, suboptimal graft quality, higher merit score, severe portal hypertension. Acceptable venous outflow. The functional graft size of this case seems to be smaller than the minimum requirement. Now, once we choose the donor and the recipient in the partial liver transplantation, these three factors are unmodifiable. On the other hand, graft inflow and graft outflow are surgically modifiable. It is very important to understand that the functional graft size can be surgically maximized by using the portal inflow modulation and the venous outflow maximization. This slide shows how to surgically modify the portal flow. We can do a splenic artery ligation, splenectomy or splenic devascularization, and portal cable shunt. The splenic artery ligation is very easy to perform, but once you ligate the splenic artery, the spleen starts seeking the arterial collaterals. So the hemodynamic effect is not as good as you want. The splenic devascularization was invented to eliminate the risk of bleeding and pancreatic fissure that frequently occurred during the splenectomy. In this procedure, you basically disconnect any arterial supply to the spleen, including the proximal splenic artery, short gastric artery, and gastric break artery. According to this study, the hemodynamic effect of splenic devascularization was as good as the splenectomy, but the risk of complication was much less. Any portal cable shunt is an elegant technique and very powerful to reduce the portal pressure and the flow. However, it is very important to keep the balance between the portal flow and the shunt flow, so the recipient frequently experiences the hepatic encephalopathy due to portal steel. To make the portal inflow modulation work better, we must have the perfect outflow. To maximize the left lobe venous outflow, we can do a venoplasty on the back table. So this slide shows the left hepatic vein and the middle hepatic vein and the left lobe graft. And we incise the septum between the two veins, and the defect is over some. So you can make the outflow of the left lobe much, much bigger. On the recipient side, the many surgeons use the left and the middle hepatic vein common channel for the left lobe implantation and close the right hepatic vein. But this is not big enough. We at the Cleveland Clinic use all three hepatic veins without exception. By using all three hepatic veins, you can create a very wide venous cuff for the anastomosis. I want to show you how to do the back table here and implantation. After venoplasty on the back table, the native liver is removed in a piggyback fashion. And all three hepatic veins are clamped together. And the septum between the three hepatic veins incised, and it creates a large cuff for the venous anastomosis. There is always a size discrepancy between the recipient and donor. Now, this slide shows the venoplasty on the right baric vein. This picture shows a fairly large right baric vein on the right rote graft, but we will make this even bigger. We create a slit incision along the vena cava groove on the right baric vein and put the venous patch around it. So you can create a fairly large venous anastomosis for the right rote. Now I want to show you our experience of adult living donor liver transplantation at the Cleveland Clinic. From 2012 to 2020, we have done 118 adult living donor liver transplantation and 45% were left rote grafts. Without exception, we always perform outflow maximization in all cases, as I show you in this presentation. For inflow modulation, we predominantly use the splenectomy. This slide shows the indications for splenectomy. The absolute indications were shown in red. So this includes estimated graft recipient body weight ratio less than 0.7%, preoperative hepatic venous pressure gradient greater than 16, marital score over 20, a large spleen, and donor age 45 years old. So when we have those factors, we do a pre-reperfusion splenectomy. For post-reperfusion splenectomy, the indications are portal vein flow greater than 250 per 100 gram of graft weight, portal vein pressure greater than 20, and the pressure gradient across the liver over 10. And also we perform the splenectomy when we have a poor hepatic artery flow in the graft, because poor hepatic artery flow is usually the surrogate for the severe portal hyperperfusion. The splenectomy was very effective to reduce the portal vein flow and the portal vein pressure. The incidence of complications were comparable between the no-splenectomy and the splenectomy, including the bleeding, portal vein thrombosis, and septic complications. Out of 118 patients, we had only one patient with small foci syndrome and 15 patients with early allograft dysfunction. The risk factor for early allograft dysfunction was the high merit score and the donor age, but the splenectomy was protective. The graft survival was excellent between the splenectomy and the no-splenectomy, and even with the graft-to-recipient body weight ratio less than 0.7 percent, we achieved an excellent outcome. As we gained experience, the average graft-to-recipient body weight ratio has gone down, and nowadays our average graft-to-recipient body weight ratio is less than 0.8 percent. Interestingly, we have been performing more pre-reperfusion splenectomy, meaning as we gained experience, we can identify the patients who required portal vein flow modulation even before implantation. This is my last slide. The functional graft size is determined by the five risk factors for small foci syndrome, such as actual graft size, graft quality, recipient disease severity, portal vein flow, and graft outflow. The functional graft size can be surgically maximized by portal vein flow modulation and graft outflow maximization. Most importantly, the understanding of the concept of functional graft size helps maximize not only the recipient outcomes, but the living donor's safety. Thank you for your attention. Hello, my name is Ryo Hirose, and I wanted to thank the organizers of ASLD, who have invited me to give a talk about potential allocation policies to promote split liver transplantation. I'm a professor of clinical surgery at the University of California, San Francisco. And although I have no financial disclosures, I do want to say I currently serve as a surgical director of SRTR. But this presentation does not reflect the views or policies of SRTR, HRSA, or HHS. In fact, these views and opinions expressed in this presentation are clearly my own personal ones and do not reflect any view or opinion of an official body. To talk about allocation policy, I wanted to just review on this slide how the policy development process works. The first thing is to gather not only ideas, but to really create a problem statement. And what is the problem and what are the goals of a new policy? And then one develops proposals. And then in UNOS, a public comment period occurs, and then many modifications are often made after the public comment process. And then after the board actually approves the policy, then there's a post-implementation plan. And so there's an analysis that's done for every policy that is created that looks at the results and examines the data. So this has to all be part of making any sort of policy proposal. So in the next 15, 20 minutes, I'm going to probably try to walk through a potential policy change that might actually facilitate at least more split liver transplantation in this country. So what is the problem? Why do we need to increase split liver transplants? The obvious answer is to make best use of every organ. So instead of one recipient, you can transplant two recipients from one graft. And the majority of splits performed in this country clearly are those in which the split occurs with the left lateral segment graft with the right trisegment split. And there are comparatively relatively few true right-left low split liver transplants performed in the United States. A related goal of increasing split liver transplants and transplanting more people in general is to reduce pediatric wait time, pediatric waitlist mortality as much as possible. And some of these policy changes that I would propose could facilitate not only more split liver transplants, but really increase the access of the smallest pediatric recipients to portioned liver grafts and hopefully decrease waitlist mortality for the most vulnerable pediatric cancer. So what is the actual extent of the problem or the magnitude? Well, clearly every year about 50 children die, 50 children every year die because of being removed from the waitlist for dying or being too sick. And this has been consistent 2016, 2017, 2018. You can see here that if you add up the patients that died and removed too sick, that's on the order of 50 patients, 50 kids a year that die on the waitlist. And what is the most vulnerable population in the pediatric population in the last 18? Clearly, those that are the youngest and the smallest have the highest waitlist mortality rates. So those are the patients that really are the most vulnerable in terms of waitlist mortality for multiple reasons. What is the current state in terms of utilization of split liver transplants? Well, year over year, it's been relatively stable. And you can see that in terms of percentage of grafts that are used, there's a much higher percentage of kids that are receiving split liver transplants. That's pretty obvious why many of these small children and the normal grafts that come from adults are too large. And often we will try to use either a paradigm or more often to split liver transplant in the smallest of children. If you look by the actual numbers, these are three-year periods comparing 2006 to 2008 to 2016 to 2018. You can see that overall, in those three-year periods, there were 1,800 or 1,700 pediatric transplants that are done. And a full 13% of them were split liver grafts in 2006, 2018. And there was somewhat more of a percentage of all the liver transplants that were splits in children. Compare that to adults where the number of split liver transplants, a very small portion of the number of transplants that were done in the United States. And this is one-year period, obviously, but still the percentage of the overall number of transplants done for adults is much less. And again, the split liver is a segment 2-3 graft, often goes to a smaller adult or child. And the right extended graft segments 1 and 4-8, much more commonly done compared to the true right and left lobe split. Now, what are some potential allocation policies to facilitate split liver transplant? In the past, a few variances have been created to quote-unquote incentivize splitting. And this involved allowing the center that accepts one part of the whole liver to allocate the other part of the graft to the same or associated center. Unfortunately, this has not consistently increased truly the number of split liver transplants done, despite this sort of incentives to split that liver. When an allocation goes to a child, however, it probably doesn't necessarily incentivize that center. It's just nice to keep the tri-segment, I guess, at your center. But the truth is, unless we redirect those livers specifically to pediatric transplants, I'm not so sure that these variances are going to actually increase split liver transplantation significantly. So my proposal is actually to preferentially allocate livers that are amenable to splitting to pediatric candidates first and foremost. So what is the actual proposed policy that I'm thinking about? Well, think about this. If you take a criteria and define what splittable livers are, they get offered to the pediatric list. And you can argue as to how small or young a pediatric candidates they have to be to get the splittable liver preferential allocation. But they're offered to them first, before adults, even before status 1A and the sickest adults, with the intent of offering the left valve segment to the child and the tri-seg to the rest of the list. And so obviously, we have to define what splittable livers are, and the devil's in detail. Which kids would it be above a certain PELD score? Would it be only children below one, below two, below six? Which children would be prioritized and how would they be prioritized? And I would argue that the tri-segment that's allowed goes down the usual allocation list as opposed to get kept at the same. So first of all, what would constitute a splittable liver? This can be determined by, obviously, those that are in the field and have done a lot of split liver transplants. Literature says that consistently, they're young donors with fairly decently low BMIs. Some folks think that DCEs are sort of pushing the edge when it comes to splittable liver. Others have used them. A fairly short downtime. Sodiums that are not too high. Human dynamically stable on mineral pressers. Not long hospital stays for diseased donors and relatively normal liver enzymes. But in terms of what livers get allocated down this pathway, we would have to agree that it's really the best donors, the young donors that are not particularly obese and are, therefore, more likely to have fatty liver change. It would be nice, also, for us to have a surgical standardization of the split, whether it's conventional anatomy, as well as some flexibility, depending on whether there's an average anatomy and just as a baseline, for example, we could agree that the left anal segment going to the child gets the aorta and the celiac axis, but also just gets the left portal vein, left hepatic vein with a patch, left hepatic duct with the right trisag graft, gets the right hepatic artery, the main portal vein and the right with the left stump and the IVC with the patch around the left vein and the common bile duct. So we can say at least there could be a standardization depending on anatomy. And I personally don't think we should mandate whether it should be an ex vivo or in situ split. Some prefer a mandate to use the in situ split technique. This may help with the decreasing ischemic times. But other centers, including ours, have successfully shared right trisegment grafts with other centers after an ex vivo split at the transplant center, particularly when the donor is very close to the transplant center. And I believe the policy should be flexible. I can give some of our data when we have imported split loaders and exported them as well. So how would it go? You allocate the split liver, splittable liver to small children and allocate the remaining graft to the oldest. It'll always require a fair amount of coordination, robust communication between the two accepting centers. Pre-recovery, there should be an understanding of what vessels that will go to which patient and the bile duct management. And if on arriving to the donor operation, liver is actually not found to be splittable or not usable for the pediatric center, it gets reallocated to the general list. So in this case, the OPO should have backup for every single split liver and the centers accepting the splits, I do think should be designated as those interested in accepting a split for their patients and eventually probably have a history of using split liver transplants. If a lot of folks say they're interested and they never accept them, but that can be worked out as well. So what would a straw person allocation sequence might be? Well, every adult split liver, however we want to define it, would get allocated to children, small children, let's say just less than six years of age. We can debate whether that should be six years or 10 years or two years, et cetera. And within 500 miles to status 1A kids, status 1B, and all the way down to appellate above a certain level within 500 miles. Then it goes down to the adults, down the sequence to adults to 500. Then beyond 500 miles, if the split of the liver goes past adults down to 29, I suggest that it gets again allocated to small children, 500 to 1,000 miles of the sickest patients before it goes down to adults again. So this is how the adult splittable liver would be, with the intent to split, be allocated preferentially to children. Whereas a right tri-segment allocation would go again down the usual pathway, status 1A out to 500 miles. And then if no one within 500 miles wants it, then that's the center themselves or with a working relationship that the Pediatric Liver Transplant Center has an adult candidate or has a working relationship with, could use it for any patient with a MELD greater than 15. This assures that the patients, the adult patients that are sicker, that is a MELD of 29, gets a shot at the tri-seg before it gets preferentially or allowed to be stayed, allowed to be kept at an associated center, at the same center as a pediatric center that is accepting the left-of-the-aisle segment for split. Now, accompanying such a policy, there has to be very important, I think, post-implementation monitoring. So I would suggest, given the small number of total pediatric weightless mortality in the country, that there be a compulsory review of every pediatric weightless mortality, particularly for those children that had offers declined. And specifically for this policy, I would certainly include a review of not only all the offers, but declines for those that are split-able liver offers that were allocated and declined, allocated under this policy and that were declined, and then eventually resulted in a pediatric weightless mortality. We obviously should review how often those split liver offers are accepted and declined and allocation of the tri-segment. How often was a tri-segment successfully used? How far down the list was it allocated? And how often did it stay with the center that accepted the left tri-seg? We should clearly see whether the transplant rates for the youngest and smallest pediatric candidates were affected and whether we actually decreased the weightless mortality for the youngest and smallest pediatric recipients. And of course, we would need to continue to follow the post-transplant outcomes for the two recipients of the split. So I actually think that we should continue to look at policies and keeping centers accountable should certain patients be preferentially allocated livers. And with the increased priority of pediatric candidates comes with it a responsibility of using the split liver graphs when appropriate. And this actually begs the question of should pediatric centers caring for the youngest candidates be able to not only do split liver transplants, but perform living donor transplants, at least for the youngest and smallest candidates? And we just want to make sure that livers, when they're offered as splits, are accepted when appropriate. And if they are declined repeatedly by pediatric centers, the reason for the declines and to see, especially if those patients that received the offers and got declined ended up dying on the wait list. In other words, I think we should really look at pediatric transplant centers in general that list candidates that are very small, for example, infants and babies. And should they at least demonstrate that they are able to use split liver transplants? And again, pediatric wait list mortalities are not that frequently centered that I think every single one of them could be reviewed. And to make sure that there are no improvements in terms of acceptance and decline path. At UCSF about 10 years ago, we published our experience at UCSF. It was 106 split liver transplants and cold ischemia time was 10 hours. When we split them at UCSF, they were all done ex vivo at UCSF and 76 grafts were generated, 31 left lateral segments and 27 right trisegs. And when we imported them, most of them were actually in situ splits. And so the cold ischemia time for those livers are nine and a half. Again, six lateral segments, one right lobe and 23 right trisegs. When we accepted the triseg from another center that took the left lateral segment. There was no significant difference in our adult pediatric patients that were either ex vivo at our institution versus an in situ split coming in from other institutions. So in summary, an allocation policy that preferentially allocates splittable livers to small pediatric recipients will likely promote and facilitate splitting more than previous variances that allow the other segments simply to be kept at the same or affiliated transplant center. Such a policy would clearly increase the access to liver grafts for the smallest pediatric liver transplant candidates, which are clearly the most vulnerable of the pediatric candidates. I believe that the triseg should be offered down the match run to protect the access to life-saving graft for the sickest adults. And once it passes through those sick adults, then the triseg, I think, should probably be able to be kept at the center or at an affiliated center. I also think that post-implementation monitoring of pediatric centers is also essential if we were to have such a policy in place. And again, review of pediatric weightless mortality and any organ offer declines of those patients that died on the list should be reviewed to identify any areas of improvement. So thank you very much and thank you for the opportunity to present my thoughts. Well, thank you to everyone for participating in this afternoon's two sessions. We have heard a lot of options for expanding the organ supply. And we thank you specifically to all our speakers in this last session, Dr. Heimbach, Dr. Reyes, Dr. Hashimoto, and Dr. Hirose. And another thank you to the speakers in the first session, Dr. Watt, Dr. Sasaki, Dr. Eggstadt, Dr. Olthoff, Dr. Tanner, and Dr. Danziger-Isaacoff. We will be going on to audience questions, Q&A for the next seven to eight minutes. But again, I would like to thank the committee for organizing this and all of the speakers. Thank you.

Surgery

Liver Transplantation Workshop

Living Donor Transplantation

Split Liver Transplantation

Dr. Heimbach

Dr. Reyes

Dr. Hashimoto

Dr. Hirose

Allocation Policies

Organ Utilization