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BackTable / Tumor Board / Podcast / Transcript #6
Podcast Transcript: Transplantation for HCC: Who, When & How?
with Dr. Heather Patton, Dr. John Seal and Dr. Steven Young
The process of liver transplantation involves many complexities, and each patient's path to transplant is unique. To offer insider perspectives on this process, Dr. Zachary Berman sits down with transplant and hepatobiliary surgeon Dr. John Seal, as well as transplant hepatologists Dr. Heather Patton and Dr. Steve Young.
Physicians, nurses, nurse practitioners, and physician assistants can follow this link to earn CME / CE credits for completing an accredited learning activity related to this discussion: https://www.cmeuniversity.com/course/take/125740 You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Defining Success for Liver Transplantation: Benchmarks & Implications
(2) Pre-Transplant Evaluation & Candidate Selection
(3) MELD-Based Prioritization & Liver Transplant Wait Times
(4) Managing Portal Vein Thrombosis in Transplant Candidates
(5) HCC Transplant Eligibility: Milan Criteria, MELD Exceptions, & Bridging Therapy
(6) TACE vs. TARE for Transplant Prep: Surgical Considerations & Downstaging Outcomes
(7) Peri-Transplant Considerations: Timing, Pumps, & Marginal Grafts
(8) Post-Transplant Surveillance: The Retreat Score
(9) Post-Transplant Challenges: Rejection & Recurrence
(10) The Future of Liver Transplantation
This podcast is supported by an educational grant from AstraZeneca Pharmaceuticals and Boston Scientific.
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[Dr. Zach Berman]
All right. Welcome, guys. We're going to be talking about the transplant approach from both surgical and medical perspectives. I'm Zach Berman. I'm an interventional radiologist at UC San Diego and I'm joined today by–
[Dr. John Seal]
I'm John Seal. I'm a transplant and hepatobiliary surgeon. I practice out in New Orleans at the Ochsner Clinic.
[Dr. Heather Patton]
I'm Heather Patton. I'm a transplant hepatologist and I practice right here in San Diego at the VA Health Care System.
[Dr. Stephen Young]
I'm Stephen Young. I'm also a transplant hepatologist. I practice with John at Ochsner in New Orleans.
[Dr. Zach Berman]
Great. Can you tell us a little bit about what your practice pattern is like? How many transplants are we doing here? How many patients are we seeing?
[Dr. John Seal] At Ochsner, we do about 150, 160 transplants a year. About 10% of that is living donor transplants. The rest are deceased donor transplants. That volume has been relatively stable for about the last 10 years or so.
[Dr. Stephen Young]
Yes. My practice is about 50% general hepatology. Anything from elevated liver tests, fatty liver, to decompensated cirrhosis, and then the other 50% or so is transplant, both pre- and post-transplant care.
[Dr. Heather Patton]
My practice is primarily general hepatology, but we do take care of pre- and post-transplant patients when they've returned from the transplant center.
(1) Defining Success for Liver Transplantation: Benchmarks & Implications
[Dr. Zach Berman]
Perfect. I think a good place to start is what's just the general data on transplantation? How is success measured? Is it one-year survival, two-year survival, five-year survival? What sort of benchmarks are we looking at trying to hit?
[Dr. Stephen Young]
I think the big ones we look at are one-year and three-year survival. I think that's what UNOS measures. We have to report other things that we look at, or graft survival, in addition to patient survival. If they develop recurrent HCC, if they're transplanted for HCC, some of the big measures we look at.
[Dr. John Seal]
Yes. I think it brings up a good point because this frames the whole therapy of transplant because with a lot of cancer therapies, if we get a 5% survival, we're like, "Oh, we made some ground." When you're talking about transplant, you have a scarce resource that's shared. The benchmark is for one-year survival, it's around 90% to 95%. Your five-year survival should still be around 80%. When we start this conversation about doing transplants for cancer, we really have to have a combination of therapies that will allow us to get the same type of survival that we get with transplant for other reasons. I think that is in the background when we talk about transplant for HCC in particular.
[Dr. Heather Patton]
I think it also helps to set a benchmark for, as cancer therapies evolve, assuming that the liver function is adequate, can we reach those same benchmarks without transplantation?
[Dr. Zach Berman]
Perfect. Since you brought up our first acronym, I'm sure of many acronyms we're going to talk today. What is UNOS?
[Dr. Stephen Young]
Yes. UNOS, United Network for Organ Sharing, they regulate transplants in the United States, not only liver, but other organs.
[Dr. Zach Berman]
Okay. Every single center reports the same place or is there regions for UNOS, or?
[Dr. Stephen Young]
Yes, there are regions, but there are certain criteria that we have to report to UNOS, both before and after transplant that are standardized for each center throughout the country.
[Dr. Zach Berman]
Whenever you get like, "We're the best center for this size," that's coming from them?
[Dr. Stephen Young]
Exactly.
(2) Pre-Transplant Evaluation & Candidate Selection
[Dr. Zach Berman]
All right. Perfect. I think that's going to set us like a good backdrop of what we're expecting for the rest of this conversation. I wanted to start off with the pre-transplant process. Someone comes in, let's just assume for right now they don't have cancer. They have chronic liver disease and, for whatever reason, we think they need a transplant for the chronic liver disease. What's the work-up like for that, both from a surgical perspective and a medical perspective?
[Dr. Heather Patton]
I'll say for the medical perspective, first and foremost, the first thing we have to answer is, do they really need a transplant? Because it's a scarce resource and if the cirrhosis is early enough, they may have superior survival without undergoing transplant. Then after that, what I like to explain to patients about the evaluation is that we want to make sure that they don't have any other health problems that would make the surgery itself too high risk or that would compromise their survival after transplant. Using examples like if you survive the transplant surgery and then a year later, die from cardiovascular disease or metastatic lung cancer or something of that nature.
Then the last bit beyond the medical evaluation is the psychosocial part, sort of do you have all of the resources that are needed to take care of a transplanted organ? Surgery is the first part. I won't say it's not the most important part to our surgeon, but for that graph to work well over the long run requires, people taking, often a number of medications, being adherent to lab monitoring and clinic visits and that type of thing. The other thing that is pertinent in this patient population often is alcohol and other substance use and making sure that those disorders have been adequately treated with a plan for long-term sobriety maintenance.
[Dr. Zach Berman]
Awesome. I guess taking that in pieces, what exactly support network do you need to have? They always talk about, at least at my tumor board, this person doesn't have a caregiver. What goes into that?
[Dr. Stephen Young]
Obviously, the medical evaluation is really important. Psychosocial evaluation is important, but equally important is the psychosocial evaluation. We have dedicated transplant social workers who meet with their patients, meet with their caregivers. Typically, we require somebody to have a primary caregiver is our terminology, so somebody that can stay with them in the peri-transplant period.
In reality, it's difficult for one person to take care of another person 24/7 after transplant. They have lives, too. They have families. They have life going on. We typically require them to have a secondary caregiver, so somebody that can fill in. Certainly people may have more than two people that can take care of them, but at least once they're discharged from the hospital, especially early after transplant, either friends or family members that are able to care for them after transplant.
[Dr. Zach Berman]
Perfect. How about from a surgical perspective? What's part of the workup for that?
[Dr. John Seal]
Yes, we all work pretty closely together. From a surgery standpoint, we routinely get imaging. Most of the time, they've had some degree of imaging going into it. That can be a little tricky sometimes because of renal function. I know you all deal with that all the time, too. That's an important part, is just to get an idea of the lay of the land. Really, one of the important things, or probably the most important thing, is to stratify how complex that operation is going to be. At our center, we use ABC classification system that helps us quickly understand when we're reviewing the list of the patients, how hard this transplant is going to be.
For an A-class patient, it means no prior upper abdominal surgery. It means all the vasculature is patent, that their BMI is in a reasonable range, and we can probably do the transplant in a couple hours. Goes pretty quickly and pretty good recovery. On the other end of the spectrum is BMI over 50, or extensive prior upper abdominal surgery. Then, of course, portal vein thrombosis makes hooking everything up a lot more complicated. Ultimately, that dictates the type of graphs that we can use down the road, which ultimately dictates how long they're going to have to wait for a liver. That's what we try to capture in the eval prog.
[Dr. Zach Berman]
Okay. They do their entire evaluation, and at least at my center, they have something called a selection meeting, where they either choose to approve or not approve somebody. Could you guys take me behind the scenes and maybe tell me what the discussion is, whether you make the final approval or not to list the patient?
[Dr. Stephen Young]
Yes. At least our selection committee, it's typically the hepatologist who presents the patient. We go through the etiology of their liver disease, the indications for liver transplantation, what complications they're having. We'll talk about their medical history, their surgical history, and then we'll run down all of the testing that was done for part of their transplant evaluation. Cardiovascular testing, routine cancer screening, things like that.
Then, at that point, we turn it over to the rest of our committee. We have social work weigh in, we ask our surgeons to weigh in. We have a financial coordinator as well, making sure that finances are in place, that people have appropriate insurance coverage for transplant. Then we also have transplant anesthesia that weighs in. Talking about the anesthesia risk associated with transplant. Then, as a committee, we determine whether or not each patient is acceptable to be approved for transplant.
[Dr. Zach Berman]
Perfect. Does it have to be a unanimous decision? Everyone has to be on board, or?
[Dr. Heather Patton]
No.
[Dr. Stephen Young]
There are lots of discussions. There are lots of things that can come up, psychosocial issues, alcohol is always a big one that comes up. It doesn't have to be unanimous, but–
[Dr. John Seal]
To be fair, we don't really vote. I don't know if this is how it goes with y'all, but it just migrates into a consensus. Occasionally, we have a split perspective on the patient's candidacy, and that will sometimes play out with more specific taking.
[Dr. Stephen Young]
Yes. It's not always a yes or no. Sometimes we defer patients, so they're either approved, declined, or deferred. We can defer them for several reasons. We can think they have increased cardiovascular risk, and they may need-- Maybe they had a stress test, and we think they need a left heart cath after discussing them. There may be psychosocial issues, alcohol, and we want them to do more rehab, maybe a formal rehab program for alcohol. There are lots of other issues that can come with it. We can defer patients, either do more testing, let the patient do more rehab or a longer period of sobriety, and then bring them back up to a later selection committee.
(3) MELD-Based Prioritization & Liver Transplant Wait Times
[Dr. Zach Berman]
Perfect. We've approved a patient, and what happens after that? Are they going to get their liver the next day, or what happens?
[Dr. John Seal]
We keep trying Amazon, and they're all out of livers, so it's not working. I even got Prime. Yes, that becomes complicated. Once they're on the list, then it depends on how sick they are, is one answer to that. Patients who come in with really decompensated liver disease and a very high MELD score can get transplanted the day after they get listed. It's never happened, but they can usually get transplanted pretty quickly.’
The trick is that we have a system that prioritizes the MELD score for highest MELD score. If you have a high MELD score, then you can get transplanted pretty quickly, but even if it's the mean for that area or below, then the waiting time is highly variable and often quite long. The reality for the patient is they just got approved, they know they need this therapy, and there's extraordinary anxiety because we can't just tell them when that's going to happen. The waiting time can vary quite a lot. I think if we think about this in terms of transplant for cancer, then there's a system by which even patients with low MELD scores will get more. We may tackle that in a little more detail. That's going to dictate also when they get transplanted.
[Dr. Zach Berman]
So it's based on MELD score?
[Dr. John Seal]
MELD score. Go home, pack a bag. We'll call you when we got one.
(4) Managing Portal Vein Thrombosis in Transplant Candidates
[Dr. Zach Berman]
Great. Building upon that, most of our patients are going to get transplanted immediately and they might have a bunch of other issues going on medically that might need to be addressed. I think the first one I want to tackle is portal vein thrombus, and we're still not in the cancer space. We'll get to the cancer space in a second.
[Dr. John Seal]
Got it.
[Dr. Zach Berman]
But portal vein thrombus, bland thrombus, just from portal hypertension, from a surgical perspective, how much is too much?
[Dr. John Seal]
We try to be as creative as possible. I think it certainly fits into several different factors coming together. We're a lot less ambitious if the BMI is 50, which is technically doing that bypass or getting that vein open and having a successful recovery period goes down tremendously. The weight and the body habitus plays in quite a lot. Most of the time, so our approach at our center is we always start with thrombectomy, intraoperative thrombectomy. If that clot is contained just to the portal vein, then most of the time-- and it looks like it isn't too chronic and organized, the calcified portal vein clot is no fun for anyone. If it's relatively fresh clot, then we'll try to do a thrombectomy. If not, we can look at bypass options. Probably the most reliable and best outcomes are with a bypass from the superior mesenteric vein where we take cadaveric vein and we make a new portal vein.
Once you get outside of those two options, now we're looking at inflow options that have much poorer outcomes. If there's a lot of collateralization between the splenic vessels and the renal vessels, typically on the left side, then you can take the left renal vein and put a conduit and bring that up for portal inflow. We've done that a couple of times. That also can be a pretty tricky operation if they had SPP or any scarring. All these options are really, you don't want to go into it with that being plan A.
[Dr. Zach Berman]
Plan A is usually you guys with anticoagulation. At least in my experience, that's how it is. How do you determine whether someone's an anticoagulation candidate with varices and other bleeding risks, thrombocytopenia, et cetera?
[Dr. Heather Patton]
I'll say, because I'm a little older than you, this has definitely changed over the course of my practice. I think we used to have a lot of fear about anticoagulating this patient population. In fact, what the data have shown, as you understand, I know, the presence of a portal vein clot is actually increasing the severity of portal hypertension. With that, you may have enlarging higher risk varices that are more likely to bleed. If you identify a clot before it's recalcitrant calcified with extensive cavernous transformation, then you actually can reduce the risk of variceal bleeding by anticoagulating.
I think most people would do an endoscopy before initiating anticoagulation. Then, the other issue is sorting out what to use to anticoagulate these patients. I think the safest is often low molecular weight heparin. The DOACs are a little bit tricky, depending on the severity of liver disease. Warfarin can be complicated because we don't know necessarily where to aim the INR target.
[Dr. Stephen Young]
Yes, I think the other thing is we don't have great data yet for the DOACs and how safe they are to use in cirrhotics. It seems to be that they're pretty safe. The other thing that we want to consider is their transplant candidacy. If they're on a DOAC and they get called in for transplant, how easy is it going to be to reverse that? One is the ease of getting the medication to the cost. The reversal agents for some of them are very expensive if they're available.
Our practice is typically to use warfarin if they're listed for transplant. That way we know that they're easily reversible if they get called in for transplant because the timing of that is unknown. Low-molecular-weight heparin is another option because that's also easily reversible. A lot of it will depend on their transplant candidacy. I agree. We definitely would want to scope them before, make sure they don't have varices, band them ideally before sorting them on anticoagulation.
[Dr. Zach Berman]
How long would you give anticoagulation a shot before you start thinking of interventions to help? Because occasionally I find ourselves doing some intervention like portal vein recanalization in order to make the transplant easier if we can get the vein open before transplant, like a TIPS portal vein recanalization. What's your guys' experience with when we think about doing that?
[Dr. Stephen Young]
Yes, that's a tough question. I think that's when we get into our multidisciplinary conferences and we talk with interventional radiology, with transplant surgery, with hepatology, want to know how easy is this going to be to be accomplished? Is this going to be an easy interventional radiology procedure? Is it going to be time-intensive, risky for the patient? Is it really going to benefit them? We've done it a few times and the ones that I've personally seen have been successful. It's definitely something that we would talk about with our whole team and not just one person saying, let's do this and go forward with it.
[Dr. Zach Berman]
Would it be three months, six months after anticoagulation, or?
[Dr. Stephen Young]
I've seen them do it even before they're on anticoagulation and then put them on anticoagulation after. I don't know if there's enough data to say what's the right answer or not.
[Dr. John Seal]
That's the big issue, is we don't actually know the answer to this question. We got to operate in that space of what do we think is safe for the patient. We certainly think about-- so preemptive TIPS, I think, is a really interesting topic, and that's emerging. We don't have great data, but I know there's a lot of centers doing it, especially like a relatively small caliber TIPS bypass just to decompress that and you get better flow and that maybe even in combination is going to help with these partial portal vein clots.
We've had a couple of pretty aggressive approaches where we knew we needed to get the portal vein open to make them a good candidate and they've done thrombectomies and the transplanting approach and opened things up. The only thing I would say is the one that has caused me a good deal of headaches-- Talk to your surgeons, your transplant surgeons, before we start TIPS'ing them because if you park that portal vein stent under the pancreas in a cirrhotic patient, that is a treacherous thing. Even though the portal vein is technically open, that is pretty treacherous to try to reconstruct around and so that's one thought that I have about it.
[Dr. Zach Berman]
Then also, from a technical perspective, at least the transplant surgeons I've worked with said the other end on the hepatic vein side, not going into the right atrium can be tricky too.
[Dr. John Seal]
Yes, please don't. Yes, we don't like to get into the chest. We leave that to our cardiac colleagues. I've only had to do that one time where we had to open the pericardium and put a clamp up high, but that's a headache. What this comes down to is having good relationships with the providers in your network and the ones that you work with so that you know to make that phone call ahead of time and you know how it's done. We get into tough situations when people get IR therapies in places who aren't familiar with transplant and don't know to avoid these sorts of things. It's great to get that out there.
[Dr. Stephen Young]
I think the other thing to bring up too is taking into consideration their liver function. If they have a high MELD score and you go in and put a TIPS in, you have a high chance of making them sicker and potentially ineligible for transplant if they get too sick or things like that. Not always putting TIPS in on somebody who's really sick. You could potentially do more harm than good.
(5) HCC Transplant Eligibility: Milan Criteria, MELD Exceptions, & Bridging Therapy
[Dr. Zach Berman]
Definitely. All right. Let's move on. Still pre-transplant, now they have cancer. How does transplant and cancer, HCC specifically, although we are transplanting for a bunch of other cancers now, specifically HCC, how does that work? Does it change how they get transplants or what?
[Dr. Stephen Young]
It does. If the sole reason for transplant is HCC, it changes definitely their wait time for transplant. The way that it works in the United States is that patients are listed at whatever their MELD score is. If somebody with HCC has a normal MELD score, say it's six and they have HCC, they'll get listed at a six. If they don't get transplanted within the first six months of transplant, which most people don't, unless there are unforeseen circumstances, then after the six-month mark, they are potentially eligible for what's called exception points, and so they get listed.
It's a little tricky now, and it changes every few years. Right now, what happens is they get listed at the median MELD minus three, where the donor passes away, which is a little tricky and difficult to understand. Basically, whatever the average MELD score is at the time of transplant, they get listed at three points less than that to help them move up on the transplant list and get transplanted.
[Dr. Zach Berman]
Definitely. Is that for all cancer patients or they have to be certain kinds or what are their criteria to get these points?
[Dr. Heather Patton]
They have to be within certain size criteria to be eligible for it, which typically we refer to as Milan criteria. We probably will discuss downstaging. Over time, we've been able to make transplants an option for HCC patients as local regional therapies have improved and we've just learned more about how to identify people who are going to do well. To be eligible for the standard exception points that we just heard, those are for cancers that are within Milan.
[Dr. Zach Berman]
Remind me, what is Milan criteria again?
[Dr. Heather Patton]
Milan criteria is a single tumor up to 5 centimeters in diameter or up to three cancers, each of which are under 3 centimeters.
[Dr. Zach Berman]
Yes, three less than three or one less than five. I think I have it in my head.
[Dr. John Seal]
We have to chime in here, too, that that's based on a study from Italy a long time ago with 46 patients. It's crazy to me that in 2020, almost five, that's what we're based on. It has played out in other validated studies, but that's crazy to me.
[Dr. Zach Berman]
Yes. Something we debate in our tumor board all the time is this concept of there's no such thing as a 19 millimeter HCC.
[Dr. John Seal]
That's a bad radiologist.
[Dr. Zach Berman]
Can someone explain to me why that's important as well?
[Dr. Stephen Young]
Yes. For exception points from UNOS, you have to have, if it's a single lesion, it has to be at least 2 centimeters to qualify for those exception points.
[Dr. Zach Berman]
Yes. At least from an IR perspective, that's super important because we have some people who get treated in the community where they're maybe not at a transplant center. They'll have a 15 millimeter tumor, 1.5 centimeter tumor. They'll get treated and they'll come to us for transplant. Then, all of a sudden, we can't transplant them because they can't get the exception points. That 2 centimeter is ingrained in my head. Anytime at tumor board, there's a 19 millimeter tumor. "Are you sure it's not 20?" Et cetera. Great. Let's say somebody is within my Milan criteria and they are UNOS T2, so 20 millimeter tumor. We start talking about bridging therapy. They're listed for transplant. Do you guys have any preference for bridging therapies or what's been your experience with all of that?
[Dr. Stephen Young]
At our center, we mostly use Y90. If it's a small tumor, and especially if it's not transplant relevant, then ablation we'll use. I think it's center specific if they're more experienced with TACE versus Y90. If you look at the ASLD guidance, they don't recommend one over the other. It's whatever your center is most comfortable with.
[Dr. Heather Patton]
These decisions are best made in a multidisciplinary tumor board conference, taking into account size, number, location, local expertise, proximity to vessels, et cetera, to decide what the best bridging treatment is. Current guidelines don't advise tear over TACE at this point for that purpose.
(6) TACE vs. TARE for Transplant Prep: Surgical Considerations & Downstaging Outcomes
[Dr. Zach Berman]
Perfect. From a surgical perspective, I've heard, whether it's true or not, I'm not a surgeon so I can't answer it, that tear has issues with adhesions and makes the surgery harder. What's been your experience with that?
[Dr. John Seal]
I don't know. I think there's two sides to that coin. Ultimately, I care about a good outcome for the patient. If they don't get good control of the tumor, they're never in the operating room for the transplant to begin with. Anecdotally, and this is not what we should necessarily make decisions on, but because we have this sort of equipoise between TACE and tear, our center has shifted in the time I've been there. Over the past 10 years, from TACE to tear, and it seems like we get much better and longer tumor controls. We're seeing more patients in the operating room, particularly in the downstaging, like you said, that we'll get to in a minute.
It causes a lot of adhesions. It's annoying for an hour. Then once you get things freed up, it has never been a point where it affects the quality of the outcome of the transplant, with a possible exception that folks who have multiple treatments with tear or TACE really can get a lot of inflammation around the artery. Sometimes when you're doing that arterial anastomosis, it's like butter, and then I'm cursing my guys. That's okay. It works out in the end. There's lots of options to fix it. Getting a transplant is what I would emphasize.
[Dr. Zach Berman]
Particularly for our downstaging patients, that's important too, because we need to have an effective therapy that they have a slightly more aggressive cancer the duration as well. I guess, what percentage of patients in your guys' experience are successfully able to be downstaged to get to transplant? Just a good start.
[Dr. Stephen Young]
Yes. I don't know an exact number, but I would say a fair number. A lot of it will depend on the tumor biology, which you don't always know up front. There are some people that have one or two lesions that you treat them. Then when you get surveillance imaging a month or three months later, they have like multiple new lesions. Obviously, that the tumor biology is going to be really difficult to control. I would say the vast majority, assuming they don't have a really aggressive tumor biology, we are able to downstage. It's pretty rare that we get people that keep popping up with new tumors that we're not able to downstage.
[Dr. John Seal]
Yes. We usually get good intrapartic control for the downstaging, the Achilles heels that something pops up in the lung or something later and gets out of the bag there.
[Dr. Stephen Young]
Right. Unfortunately, sometimes it's post-transplant when we see that.
[Dr. John Seal]
We'll get to that too.
(7) Peri-Transplant Considerations: Timing, Pumps, & Marginal Grafts
[Dr. Zach Berman]
Great. Let's make a little transition now from pre-transplant to peri-transplant. What's the day like for someone getting a transplant, the patient?
[Dr. John Seal]
Yes, that is highly variable. It's obviously a big day for the patient. There's a lot of new technologies that change that experience as well. In most cases, they have been waiting on the list for a variable amount of time. They get a phone call and they have to come in and every situation is a little bit different. We have some cases where it's a very last-minute offer. It's very rushed. It's very stressful. They come in and get transplanted. In other cases, we know that there is an organ available. They come in to get their transplant and we'll wait even days before the donor goes to the OR.
That can vary quite a bit. We try to avoid that stressful situation where they're rushed in to get a transplant. You made an allusion to some of the pumping technologies that gives us a little bit more control over when we do those cases and do them during the daytime and doing it in a little more controlled fashion. The other variable that can really be stressful for patients is we often have a marginal graft that we think is going to potentially be a good option. They will come in and they can drive in multiple hours, sit in the hospital for two days, only to have it be not a good graft. We end up having some of our patients on the list get called in even dozens of time and that can really wear on people psychologically.
We know when people are going to get transplanted if they have a living donor. With living donor transplant, then they already have that date scheduled, and the anxiety is really lowest with that.
[Dr. Zach Berman]
Who can get a living donor transplant?
[Dr. John Seal]
Anybody is the first answer. There's very few cases where you can't. Maybe in some centers, when there's complex portal vein thrombosis or liver retransplant, those would probably be some of the hard stops where we wouldn't do it. At least we wouldn't at our center. There's a couple centers that do even do it in those situations. The trick is that not every center does living donation. It's not an option everywhere. We have to figure out how to connect patients who have donors with centers that do them.
[Dr. Zach Berman]
Awesome. You mentioned this pump. What is this pump?
[Dr. John Seal]
Yes, the pump. Your hometown here are one of the national leaders in that. There's this explosion that happened in liver transplant over the past two or three years based on this idea that once an organ is recovered, the liver, you can sustain it outside of the donor's body on a circuit of blood and keep it oxygenated and keep it warm. That's really important because it gives you metabolic function from the liver and you can do further assessments and you can keep it stable for longer periods of time.
All those cases where you're ready to start the transplant at 11:00 PM, they start to go away. You do it at 6:00 AM, and you have more information about the quality of the graft before you sew it in. It allows you to take a lot of those marginal organs that I talked about and if you need more information about it, you put it on a pump and you can take organs that would normally be buried and put them in the carefully selected patients. It's really revolutionary. It's super tricky. We need like eight sessions to go into the finances of this because it's quadrupling the cost of transplants and if you had a CFO in here, they would be up in arms. Again, we're all trying to find out the best system we can do to take care of patients and pumps are the future for sure.
[Dr. Zach Berman]
Awesome. Speaking of marginal grafts, a lot of my patients are, at least I read your guys' notes and they say, willing to accept like a hepatitis C transplant. Do you only give a hepatitis C positive organ to somebody who has hepatitis C or can anyone get it?
[Dr. Heather Patton]
It used to be the case that we would only consider transplanting a hep C positive organ into a hep C positive recipient. But the advent of highly effective, safe hep C therapies, the DAAs have completely changed that equation where now it can be considered to be transplanted into anybody. Now there has to be an informed discussion with the person on the wait list to see if they would want to consider that and understand what that means and potential risks of it. I think has, maybe not as much as the pump, but certainly helped to expand the donor pool.
[Dr. Zach Berman]
What about HIV? Are we able to use HIV positive livers into HIV-positive patients, or?
[Dr. Heather Patton]
I think, and you guys might know better than me. It depends on the center, I think.
[Dr. Stephen Young]
Yes. It has to be somebody who already has HIV. An HIV positive liver going to an HIV positive recipient. We can't put an HIV positive donor to somebody who doesn't have HIV.
[Dr. John Seal]
Can't and wouldn't.
[Dr. Stephen Young]
Correct. And would not. Correct.
[Dr. John Seal]
Good.
[Dr. Heather Patton]
Are all centers doing or selected centers doing HIV–
[Dr. John Seal]
It's pretty liberalized now. In the trial, if we were in the trial phase and so we've been doing it for a little while. It doesn't come up in that much, but hey, every liver counts. It's pretty exciting when you can do that.
(8) Post-Transplant Surveillance: The Retreat Score
[Dr. Zach Berman]
Awesome. In the last few minutes we have, let's move now from the peri-transplant period to the post-transplant period for patients who have tumors. I know a score is calculated, called retreat. I don't know if any of you guys could explain what retreat is.
[Dr. Heather Patton]
Retreat is a scoring system that was developed at UCSF where they've done a lot of the landmark research around transplant for HCC and looked at a number of factors to see if they could help predict the risk for HCC recurrence. Catch me if I forget some of these, but the AFP at the time of transplant, the amount of viable tumor on X plant, I think they look at things like a vascular invasion, things that would speak to a more aggressive advanced tumor that is going to be associated with a higher risk of recurrence. That, then, can be used to inform how patients are surveyed and for what duration.
[Dr. Zach Berman]
Is that universally used or are there any other scores that people use?
[Dr. Stephen Young]
It's really center dependent. We at Ochsner don't rely strictly on the retreat score. It comes up occasionally, but we look at some of those same things, is there a viable tumor on X plant? Part of our multidisciplinary approach is to review all of our X plants and a pathology conference, which is multidisciplinary. Seeing if there's any viable tumor, vascular invasion, sort of the same things that were mentioned and based on that determines if we monitor them for 5 years or 10 years after transplant.
[Dr. Zach Berman]
With imaging?
[Dr. Stephen Young] With imaging and AFP.
[Dr. John Seal]
Yes. At the end of the day, it's like, what are you going to do with that information? You're going to get a CT scan every three months or six months? That's largely what it dictates. We have some systemic therapies, but most of them you can't use in the setting of immunosuppression, anyway. I think it doesn't change clinical practice that much, whether you strictly use it or not.
[Dr. Stephen Young]
Yes. I think the big thing is they, I want to say they stopped screening some patients at two years if they're really low risk.
[Dr. Heather Patton]
I want to say, I haven't looked at the original study in a while, but I think they were even arguing that if you were a zero, that you didn't need any surveillance. Though, I think even the lead investigator was like, we're not really comfortable.
[Dr. John Seal]
No, we got it all. Are you sure? Yes. Can we check? Sure, we can check.
(9) Post-Transplant Challenges: Rejection & Recurrence
[Dr. Zach Berman]
Something that plagues us, as you alluded to, is recurrence after transplant is, let's say, extra hepatic recurrence. Is repeat surgery ever an option?
[Dr. John Seal]
Oh, it's an option for sure. I haven't surveyed the literature on that recently too much, but certainly the studies that I'm aware of show really not great outcomes if it's extra hepatic recurrence. Even going back in to operate on a liver post-transplant, my hunch is that the tools we have that are less invasive are going to get you the same outcome and survival as opposed to going back in and doing surgery for intra-hepatic recurrence.
[Dr. Zach Berman]
Stepping away from the tumors again, what are sort of complications post-transplant we could run into anatomically?
[Dr. John Seal]
I don't have any, so you shouldn't ask. No, this is a tough-- there are really challenging to manage complications and we lean really heavily on our interventional group to help manage those because it has shifted tremendously again over the past 10 years where a lot of these were reoperations that were really difficult and didn't have necessarily great outcomes. Probably most common would be biliary stricturing and some of that can be done endoscopically, but often when you have complex cases, it requires PTC tubes to be placed and serial dilations of strictures.
It's really important in the context of living donation. The one Achilles heel of living donation is the bile duct perfusion isn't quite as good as a normal bile duct and stricturing is a lot more common. Interventional management of those is really key and bails us out. Then, for arterial narrowing, we also work with our interventional group at our center that do all of our stenting that narrows every time.
[Dr. Zach Berman]
How about immunosuppression? How does immunosuppression work? Is it continuous for the rest of their life? Does it change over time? How does that work?
[Dr. Heather Patton]
For most people, it is for the rest of their lives. There have been some studies suggesting that there are some patients who may be able to be completely weaned off, but that's not widely practiced. The amount of immunosuppression certainly decreases from the time post-transplant. The risk of rejection is highest at the time of transplant and then lowers over time. They start off on, again, very center dependent what the protocol is exactly, but usually a calcineurin inhibitor like tacrolimus and anti-proliferative like mycophenolate mofetil, and then some steroids. Then, over time, the steroids are peeled off, the MMF gets peeled off, and people, for the most part over the long run, get maintained on a single agent.
[Dr. Zach Berman]
Great.
[Dr. John Seal]
I think the caveat there is probably beyond the scope of this, but transplant impedes, so small kids with tumors, they are the most likely group to develop some degree of tolerance and come off completely. There's a lot happening there, but that's a small piece of the pie.
[Dr. Stephen Young]
There's other things that we factor into as well, like their kidney function. The CNIs tend to have more nephrotoxicity, and so somebody who may have CKD, either pre-transplant or post-transplant, sometimes we'll keep them on MMF or another agent like the mTOR inhibitors to try to lower their CNI.
[Dr. Zach Berman]
I personally do a lot of biopsies to rule out rejection. I think that just might be more of a reflection. We do a lot of transplants and even a small percentage of a lot is still going to be a lot, at least in my perspective. How do you guys manage that? Let's say someone has some sort of rejection. I guess, what are the types of rejection you can get?
[Dr. Stephen Young]
Yes, so with liver, it's usually acute cellular rejection. It's pretty rare for us to run into antibody-mediated rejection. Some patients, especially with mild rejection, just increasing their immunosuppression. Their oral immunosuppression is enough to control the rejection, so increasing their tacrolimus a little bit, increasing their CellCept may be enough. If it's moderate or definitely severe rejection, that typically requires IV steroids. We'll hospitalize them, give them a few days of IV steroids, try to bump up their oral immunosuppression as well. Then, typically, we'll keep them on two agents. We'll keep them on steroids for a while, and then once that's weaned off, we'll keep them on both the CNI and typically MMF is our second agent that we use.
[Dr. Zach Berman]
If that fails and we start talking about retransplant. How is that discussion had? Do they get points again or how does it work for someone who needs a retransplant?
[Dr. Stephen Young]
It's pretty rare that we run into that, thankfully. The times that we do is typically patients who are not very compliant with their medications and they run into multiple episodes of rejection and they end up getting chronic rejection, which is a little bit different than cellular rejection. It really depends on the reason for it. If it's somebody who's noncompliant and after going through a re-evaluation or deemed to be an acceptable candidate, they may be able to be managed the same way we would manage somebody that had their first transplant, obviously with more instructions on compliance and things like that.
Sometimes we run into it with people who have really difficult to control autoimmune hepatitis and they just have a really robust immune system and they run into lots of rejection. Those patients we typically will keep on two agents and sometimes we even have people that need to be on three agents to decrease the risk of rejection.
[Dr. Zach Berman]
From a surgical perspective, retransplantation?
[Dr. John Seal] Yes, again, it depends on the reason and the indication. The one that is really challenging to deal with is, we try to maximize utilization of the donor pool. That means we're using some grafts that have some risk factors. Unfortunately, some of those grafts end up developing ischemic cholangiopathy, which I know you'll see, and we try to manage that as best we can. Those are the patients that probably suffer the most on the retransplant, because they often get stuck with a low MELD score. Depending on the circumstances, they may not be eligible for extra points, and they really sit there and suffer until we find some circumstance that we can get them re-transplanted.
Those are really difficult. The management of those is also very multidisciplinary, and it can sometimes be improved or temporized with some of the interventional procedures that y'all do, but that's the one that's probably the biggest pickle.
(10) The Future of Liver Transplantation
[Dr. Zach Berman]
As we finish up, is there any last-minute big thing we need to know that's in the pike that's coming in transplant? Any new innovations that either increase the amount of livers that we have or change how well they do afterwards?
[Dr. Stephen Young]
COMPASS is still the most exciting thing, and it's not widespread. I think that's what we're focused on now. I'm not aware of other devices or things.
[Dr. John Seal]
Yes, I think there's a couple ways to look at that. One big thing is going to be transplanting fewer people, hopefully. We have to remember, we just basically cured hep C. Everything has shifted so much recently. It used to be all hep C, and you couldn't fix it. A little bit of acknowledgment that there's a lot of medical progress. Not transplanting people would really be awesome, although not until my kids finish college. Then we can stop that.
The pump game is great. The living donor game is great. If we want to do pie-in-the-sky, we got to look at things like organ engineering and xenotransplantation, and they're not really ready for prime-time, but they're not ridiculous ideas. That's something that would be neat to see in the future.
[Dr. Zach Berman]
Xenotransplantation is like pig livers?
[Dr. John Seal]
Like pigs, yes. Yes, pig livers. Obviously there's a lot of barriers to making that happen, but you've probably seen in the news media that's happened with the kidney a couple of times. There's a lot of research into that. I'm not the one doing it, but if we can find a solution for our organ shortage, then we can treat patients in the way they should be treated regardless of waiting time and issues like that.
Podcast Contributors
Dr. Heather Patton
Dr. Heather Patton is a transplant hepatologist and professor of medicine with UC San Diego in California.
Dr. John Seal
Dr. John Seal is a transplant and hepatobiliary surgeon with Ochsner Health in New Orlean, Louisiana.
Dr. Steven Young
Dr. Steven Young is a transplant hepatologist with Ochsner Health in New Orleans, Louisiana.
Dr. Zach Berman
Dr. Zachary Berman is an interventional radiologist at the University of California San Diego in San Diego, California.
Cite This Podcast
BackTable, LLC (Producer). (2025, January 17). Ep. 6 – Transplantation for HCC: Who, When & How? [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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