Melanie Cole, MS: Welcome to Back to Health, your source for the latest in health, wellness, and medical care. Keeping you informed so you can make informed healthcare choices for yourself and your whole family. Back to Health features conversations about trending health topics and medical breakthroughs from our team of world-renowned physicians at Weill Cornell Medicine.

Host: I'm Melanie Cole. And joining me today, we have a panel with Dr. Benjamin Samstein, he's the Chief of Liver Transplantation at Weill Cornell Medicine; Dr. Danielle Brandman, she's the Medical Director at the Center for Liver Disease and Transplantation at Weill Cornell Medicine; and Dr. Jim Chevalier, he's an Assistant Professor of Medicine in Clinical Surgery at Weill Cornell Medicine. And they are all here to highlight polycystic kidney and liver diseases for us today.

Doctors, it's such a pleasure to have you join us. Dr. Chevalier, let's start with you. Can you tell the audience what are considered polycystic kidney and liver diseases? What does polycystic mean and how common are these?

James Chevalier, MD: Polycystic kidney disease is a genetic disease. It affects more than half a million Americans. Unfortunately, there is no cure as of now. As the patient gets older, cysts continue to grow and to take over the normal kidney tissue. More than half of the patients will reach kidney failure by the age of 60. Despite having cysts in the kidneys, we also look for cysts or complications in other organs of the body. By the age of 50, almost 100% of patients will have cysts in their liver. Some patients get so many cysts in their liver that they need to see a liver specialist to take care of the complications of liver cysts in polycystic kidney disease.

Host: Dr. Brandman, I'd like you to break down the difference between the two. Are they equally rare or common? Explain to the listeners, because we hear about the kidney, we hear about the liver, and a lot of listeners don't even really know what those two do for a living. So, explain a little bit about the difference.

Danielle Brandman, MD: So like Dr. Chevalier said, in patients with polycystic kidney disease, pretty much all of the patients will eventually develop cys in the liver. We tend to see more cysts and larger cysts in women, most likely because of the impact of female hormones, estrogen. We also do see polycystic liver disease in isolation. And the true prevalence is really not known. We sometimes find out about these liver cysts really at autopsy or if people are getting scans for some other reason and we just happen to find them.

Guest 2: Even when patients develop really massive liver cysts, really taking up the entire volume of the liver when there's almost no normal liver tissue, surprisingly, we tend to see these patients have completely normal liver function unless they have some other underlying chronic liver disease such as alcohol-related liver disease, fatty liver or viral hepatitis. And the main problem we see in the patients who have polycystic livers, regardless of whether it's an association with PKD or in isolation, are a lot of symptoms of an enlarging liver and feeling very full. And some patients will have a lot of pain related to their massive livers.

Melanie Cole, MS: Well then, Dr. Samstein, based on what the other two doctors have told us about these, are they dangerous? What complications do they cause if some people may not even know that they have them? Are there symptoms that they present with? How would we know?

Benjamin Samstein, MD: That's a really good question and one that I think why it's important to be seen by people who have a lot of experience with polycystic disease. Patients with polycystic disease are more likely to present with organ failure than patients who have polycystic liver presenting with liver failure. In the liver, they're more likely to present with symptoms from their cyst size. And so, the symptoms we send to see are inability to eat, pain. But cysts in both organs can lead to infections. They can lead to compression of the other organs. Typically, patients, if they don't know that they have polycystic disease, their symptoms can not necessarily be immediately attributed to their cyst disease. It can be difficult to tease out what the impact of the cysts are in causing their symptomatology of their symptoms. If it's an infection, it may be more easy to tell. But if it's the compression of that organ on other organs, it can be difficult to tell whether or not it's a cyst or other disease in that other organ that's causing the problem.

Guest 1: I agree with Ben. I think that at our PKD Center, we follow pictures and images of the organs of the abdomen over time. So, sometimes we might notice that the kidneys or other organs are enlarging from all the cysts. Sometimes we might see one dominant cyst, for example, in the liver, that we think that Dr. Brandman or Dr. Samstein could help the patient feel better with. Sometimes the entire liver could be entirely enlarged, and that might give the symptoms that Dr. Brandman and Dr. Samstein are talking about. And again, they might be able to help with some of the symptoms of the large cysts.

At our center, we're lucky enough to have a center of excellence with a lot of other doctors from other specialties that help our PKD patients. The liver is one of the top organs where patients get symptoms. The usual reason that we would refer a PKD patient to Dr. Brandman and Dr. Samstein is lots of cysts throughout the liver causing the symptoms described or one big dominant cyst that might be able to be treated.

Guest 2: I think really an important point is that the management, at least of polycystic liver disease, is largely symptom-driven. I think patients get really worried when they hear or see that they have these really large cysts on their scans and they worry what does the future hold for them. And I really try to reassure them that whatever we're going to do is based on what symptoms they have. And I always give an example of family members who both had polycystic kidney and liver disease. And if I'd close my eyes and put my hands on both of their abdomens, it would feel exactly the same, where one patient, however, was very, very symptomatic and the other patient really had no symptoms at all related to the cyst in their liver.

Host: This is so interesting, Dr. Brandman, if this is a genetic condition, would genetic testing help to mitigate the progression in any way? Would we know about this? For a woman, how likely is she to pass this on to her children? Tell us a little bit about how that all goes together.

Guest 2: So, there are well-known mutations associated with polycystic kidney disease. I think a lot of times when the patients are being seen in the PKD clinic by Dr. Chevalier, there really is a discussion about whether genetic testing would be beneficial for really defining what is this patient's disease course is going to look like from the kidney perspective. On the liver side of things, particularly if someone has just isolated polycystic liver disease, I personally don't think that there's as much of a role for genetic testing in part because polycystic liver disease does not have an impact on liver function and the expression of symptoms is really quite variable, though certainly patients do really want to have this information for the purposes of family planning. Most of these cases are what we call autosomal dominant, meaning that there only has to be one mutation in the gene rather than two from the mother and father, basically, in order for patients to manifest the disease, meaning that if a couple is planning a family, there's about a 25% chance that they may pass on the disease to their offspring.

Guest 1: I wanted to just add a little bit more to what Dr. Brandman said and sort of highlight some of the most important things that she said. In my line of work, most of the polycystic kidney disease is autosomal dominant. So, the children have a 50/50 chance of having the disease. In the year 2023, we're actually able to help patients prevent passing the PKD gene onto their children. We offer genetic counseling to all of our PKD patients and offer genetic testing through our genetics department. If the patient does find their PKD gene mutation with the help of in vitro fertilization or IVF, it's possible to prevent the children from having PKD. I think that this is one of the things that hasn't really been publicized well in the general public, and it's one of the things that we focus on to help patients make decisions about having children in the future.

Guest 3: Let me ask a question. What percentage of patients with PLD are those patients? Is it just that they have polycystic kidney disease and their phenotype is just different? Or is it that they actually have a different disease?

Guest 2: So, for people with polycystic liver disease in isolation, there are different genetic mutations that have been identified. But when I do see someone who is sent to me because of cysts in the liver, and if they really look like they have truly polycystic liver disease, I will order an MRI because MRI can be more sensitive to actually detect some of the renal cysts and we can look at the volumes of the kidneys. So, I would say if I see isolated polycystic liver disease, I really want to make sure it is truly isolated. Because again, I think it would be wrong to miss PKD.

Guest 1: When we do the genetic testing, the standard first panel is six genes plus an additional one. Autosomal dominant PKD1 and PKD2 are at the top of the list. But then, the other four sometimes have more liver cyst-dominant than kidney cyst-dominant disease. All that being said, even if someone has the traditional PKD1 and PKD2 genes, it's very common for some people to get more liver manifestations than others. In fact, I might go so far to say most of my PKD patients have either a liver which is disproportionately large compared to other PKD patients or kidneys that are disproportionately large to other PKD patients. It's pretty rare or uncommon like the number of patients we have that have both extremely large kidneys and liver compared to the PKD population that need a combined liver and kidney transplant is a very, very small percentage of our total PKD population.

Guest 3: What I take away from some of what we're trying to convey to patients is that this is a condition that often affects people in different ways, even within their own family, that there are different manifestations within a family. It is often a disease that affects many family members and some people really want to have genetic testing. They sometimes want to exclude or prevented in their future generations. And I think that's something we offer here that is important, as well as having experts in both genetics, kidney disease, liver disease and interventional therapies that might play a role in symptomatic liver disease.

Host: That was an excellent explanation. Dr. Chevalier, did you have something to add?

Guest 1: I think that one of the things the patients would really like to know is to hear from Dr. Samstein how he actually takes care of one of these dominant cysts. I think a question that I get all the time is, "What is Dr. Samstein going to do to my dominant cyst that's causing me symptoms? How is he going to make it go away? And how is he going to prevent it from coming back?"

Guest 3: Well, that's a great question, Jim. I think that what we try to do as we look at the imaging, and this is where really carefully talking to the patient about what their symptomatology is and looking at their imaging is important. Because there are a couple different scenarios. One is one in which a dominant cyst is consistent with the patient's symptoms and we can essentially resect that cyst using minimally invasive surgical techniques and cause the cyst to be massively shrunken in size, usually reduced by more than 90%. And in those cases, the patient's symptoms will really improve dramatically. But at the same time, there are definitely cases where there isn't a dominant cyst where there's almost innumerable cysts and there's no single dominant cyst. Then, we really try to tease out how much any surgical intervention will help and what surgical options we can offer, and make sure that we're availing patients of all options.

I will say, I want to add that one of the challenges to cyst disease is that if we drain the cysts, they often come back relatively quickly. And since many of the patients are relatively young, that really is something that should be considered, is how durable is the treatment that we're going to have going to be on their symptoms.

Guest 1: I think another question I get asked a lot, which probably is for Dr. Brandman, is like everybody has cyt in their liver, how do I know that I need to see a liver specialist? Do you go by like the total volume or do you go by the number of cysts in the liver?

Guest 2: Yeah. When I look at patients who have cysts in the liver, and we get a lot of referrals for liver cysts, but not necessarily all of them are going to be polycystic liver disease. I look at really how involved is the liver with cysts. And most of the patients that I think would benefit from seeing me are certainly those who have widespread cyst throughout the liver with relatively small volumes of residual normal liver. And those are the patients who really are the most symptomatic. In those cases, sometimes the patients really just want education about their disease. And I think as patients have more knowledge about their disease, they feel more in control and I think that's really valuable to them.

And I think they also want to talk about what are the things that they can do to prevent their disease from progressing. So certainly, the patients I see do tend to have more advanced disease. But sometimes I do talk with them about medications that may help to slow down their disease progression. There are some injectable medications that are not currently FDA approved, but we can sometimes use. And they're in the family of drugs called somatostatin analogs and octreotide, is one of the oldest ones that we've used. And these are injectable medications that can be injected either three times a day for the short-acting version or, more commonly, we would use a monthly injection. These medications can actually reduce the liver volume, and that reduction in the liver volume can be associated with improvement in symptoms. And this has been studied in a few different research studies and there's actually an ongoing trial here at Cornell to look at one of these medications to see can we actually get FDA approval for the drug for these patient.

I think the other thing that patients want to talk about or want to know more about with their liver diseases is, "Will I ever need a liver transplant?" And that's really challenging to predict on an individual basis, particularly if the patient doesn't already have advanced disease. But what I tell patients is that other than this injectable medication. We don't have great ways to prevent progression of the liver cyst. The only other advice I give them is for women trying to avoid estrogen since that may promote growth. But if patients get to the point where the liver cyst completely involves the liver, and they have symptoms, that are signs of malnutrition, meaning that they have muscle wasting, and other blood tests markers that they are malnourished or if they're showing signs that their massive liver is causing high pressure in the liver to the point where fluid may be leaking out into the abdomen. Those are signs that we might actually need to do a liver transplantation. Very few patients really get to that point, but it is a conversation that I have with patients that it is a tool that we have to actually fix their disease. And thankfully, there is a really good mechanism at the national level to get these patients access to liver transplant pretty quickly.

Guest 1: At the first visit, we usually do review medications. One of the things that we suggest is they change any birth control options from estrogen-based to a progesterone-only pill or shots or an IUD or maybe barrier method. And we also suggest that women do not use hormone replacement therapy. Is there anything more than that that you suggest?

Guest 2: Unfortunately not. I wish there were. The question that every single patient asks me is, "Is there something that I can eat or drink that will help my liver cyst? Or is there something that's going to harm it? And based on what we know at this point, we don't think that there are any specific dietary recommendations for people with polycystic liver disease. So, the general advice I give is really what everyone should be doing, which is avoiding foods that have excess sugars, and trying to avoid foods that have a lot of saturated fats.

Host: This is so interesting and for patients hearing from you all is so informative and educational. I'd love for you each to offer a final thought. Dr. Samstein, starting with you, please tell patients what you would like them to know as we're talking about these polycystic kidney and liver diseases. What would you like them to know about the multidisciplinary approach and the work that you're doing at Weill Cornell Medicine?

Guest 3: I think you, you know, what you've heard today, and I think what's really important in caring for anybody with this condition is hearing that you'll be cared for. This is a relatively uncommon condition, and you really want to go to a center where there's a lot of expertise. That includes kidney specialists, liver specialists, genetics specialists and surgeons who can offer you everything from medical therapy and avoidance of worsening symptoms to the most significant surgical therapies.

Host: And Dr. Brandman, next to you, what would you like to add to this?

Guest 2: I agree that having a center of excellence for PKD management here at Cornell is really a strength and a great resource for patients. Because I would say most gastroenterologists may see only a handful of patients with polycystic liver disease in their career, whereas here I see several per week. I think it's very reassuring to the patients to know that we know what to expect with this disease and we have the appropriate expertise to offer them. And again, to really reassure the patients, your liver is not going to fail. This disease is not going to turn into cancer. And finally, that there is ongoing research for polycystic liver disease, that we are constantly working towards finding treatments that are going to really impact their long-term outcomes, particularly with regard to their quality of life.

Host: Dr. Chevalier, last word to you. And I'm hoping that you will let the listeners know as Dr. Brandman and Samstein just did, that there is hope, that this is not something to be afraid of, but that there are treatments and that you're all on the case here.

Guest 1: Definitely. And I will echo and reinforce what they said. PKD is not a common disease. Every patient with PKD really needs to go to a center of excellence. Even if it's not my center of excellence, you need to go to a center of excellence where the doctors know what they're doing and have lots of resources and specialists to help them. If you're in the greater New York City area, you're welcome to come see us here at the PKD Center of Excellence. You can call Susan our patient navigator at 646-317-0715.

Melanie Cole, MS: Thank you all for such great information. Wow, it was so informative. And Weill Cornell Medicine continues to see our patients in person as well as through video visits. And you can be confident of the safety of your appointments at Weill Cornell Medicine. That concludes today's episode of Back to Health. We'd like to invite our audience to download, subscribe, rate, and review Back to Health on Apple Podcast, Spotify and Google Podcast. For more health tips, go to weillcornell.org and search podcasts. And parents, don't forget to check out our Kids Health Cast. I'm Melanie Cole.

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