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BackTable / Tumor Board / Article
Managing Post-Liver Transplant Complications in HCC: From Recurrence to Rejection
Sophie Frankenthal • Updated May 9, 2025 • 39 hits
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading indication for liver transplantation. Transplantation offers a potential cure by addressing both the tumor and underlying liver disease, with five-year survival exceeding 70% among patients who meet selection criteria. However, long term management remains complex, with challenges including HCC recurrence, anatomical complications, and lifelong immunosuppression.
Transplant surgeons and liver disease experts Dr. John Seal, Dr. Heather Patten, and Dr. Stephen Young offer practical strategies for detecting and managing these common post-transplant complications.This article features excerpts from the BackTable Tumor Board Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.
The BackTable Tumor Board Brief
• Post-transplant HCC recurrence is particularly challenging to treat, especially in cases of extrahepatic recurrence. Surveillance is guided by risk factors like vascular invasion and tumor viability on explant.
• RETREAT scores can be used to estimate recurrence risk, though their use is center-dependent and often supplemented by multidisciplinary pathology review.
• Anatomical complications like biliary strictures and arterial narrowing are increasingly managed by interventional radiology, particularly in living donor recipients.
• Lifelong immunosuppression is standard post-transplant, with rejection managed by therapy adjustment or IV steroids. Reimplantation is rare, but complicated by low MELD scores and marginal graft allocation.
Table of Contents
(1) Post-Transplant HCC Recurrence: Surveillance & Management
(2) Anatomical Liver Transplant Complications
(3) Liver Transplant Immunosuppression & Rejection Management
Post-Transplant HCC Recurrence: Surveillance & Management
Hepatocellular Carcinoma (HCC) recurrence after liver transplant is difficult to manage, particularly in the case of extrahepatic recurrence, where surgical resection offers poor outcomes. Although intrahepatic recurrence may be treated surgically, less invasive approaches often yield similar survival and are therefore preferred.
Post-transplant surveillance guides risk stratification assessments. The RETREAT score, a risk assessment tool developed at UCSF, incorporates variables like alpha fetoprotein (AFP) at transplant, viable tumor on explant, and vascular invasion to estimate recurrence risk. Its use varies by transplant center, with many teams favoring multidisciplinary pathology review over strict score-based protocols. Surveillance strategies, such as imaging frequency and duration, are typically dictated by markers of acuity and staging like vascular invasion or tumor viability. Some centers monitor high-risk patients for 5-10 years following liver transplantation, while they may terminate surveillance in low-risk patients after 2 years – this remains highly variable based on both surgical center and patient risk assessment. Clinical decisions are also sometimes driven by the limited use of systemic therapies in immunosuppressed patients.
[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. 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.
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Anatomical Liver Transplant Complications
In addition to the risk for HCC recurrence, post-liver transplant management also requires navigating a variety of anatomical complications. Biliary strictures – narrowing of the bile ducts due to scarring or blockage – are among the most common anatomic issues, particularly in living donor transplants due to suboptimal bile duct perfusion. Both biliary strictures and arterial narrowing are increasingly managed by interventional radiology, reducing the need for complex reoperations. Whereas complex strictures may require PTC tubes and serial dilations, arterial narrowing is typically managed by basic stenting.
[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.
Liver Transplant Immunosuppression & Rejection Management
Liver transplant recipients typically require lifelong immunosuppression to reduce rejection risk, though dosing is often tapered over time based on kidney function and individual rejection risk. Standard regimens include administration of tacrolimus, mycophenolate mofetil (MMF), and steroids, with most patients eventually maintained on monotherapy. Select populations, such as pediatric recipients, may develop partial tolerance and discontinue therapy.
Acute cellular rejection is the most common form of organ rejection and typically responds to increased immunosuppression or IV steroids. Chronic rejection, often linked to medication nonadherence or autoimmune hepatitis, may require retransplantation. These patients are re-evaluated for eligibility but often carry low MELD scores, increasing their chances of receiving marginal grafts and developing ischemic cholangiopathy. Management is multidisciplinary, frequently involving interventional procedures while awaiting retransplant.
[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.
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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