Announcer:
0:00
Welcome to the MedEvidence! podcast. This episode is a rebroadcast from a live MedEvidence! presentation.
Dr. Michael Koren:
0:06
I'm really excited to welcome Dr Kapila to our MedEvidence! program. He's a rising star in this community, a brilliant, brilliant physician who specializes in liver disease, and he's going to educate all of us about liver disease, including me. And the first question I'm going to ask you is can you live without the liver? No, no, you cannot. Okay, well, there you go. So you've heard it from the experts, so we're going to talk about why your liver is important and why you should take good care of it. So this is the first time you're doing this program yeah, first time. And what we like to tell our folks is that, even though they're enjoying some food, there's no such thing as a free lunch. That's right, all right. So everybody's got to work here, okay, and everybody's got to be involved. So we like to start by doing some audience participation questions. So here we go.
Dr. Michael Koren:
0:54
The first question which of the following is not a function of liver? Is it A: detoxifying harmful substances? Is it B: producing bile for digestion? Is it C: regretting that fourth alcoholic drink, so you don't have to? Is it D: producing insulin or E: storing glucose as glycogen? So what do you guys think? All right, I heard one E, but I think most people said C, and that is absolutely correct. All right. Next question what are the ways to push your liver towards early retirement? I'm sure that's what you deal with. Is people that have done that? Yep, is it A: avoiding hepatitis testing. B: heavy long-term alcohol consumption. Is it C: eating an excessive amount of kale. Is it D: ignoring signs of jaundice and fatigue? Or is it E: A, B and D? This is a really smart audience. It is.
Dr. Nikhil Kapila:
2:00
Absolutely or all of the above.
Dr. Michael Koren:
2:10
Right, well, there's an extra one there. But they even knew it before even seeing the last option. So that's how you know they were smart. All right, so I think, with that introduction, I give the floor to you. And why don't you explain to us how the liver is an example of form meeting function?
Dr. Nikhil Kapila:
2:17
yeah, I mean. I mean the liver is well, Dr. Koen, First of all, thank you guys for the invitation to speak to you all. I mean, it's a it's an honor and a privilege to be here and to share some of my knowledge I have about the world of hepatology. You know, today it's going to be a whirlwind tour about what the liver is, what it does and why it's so important for you know your everyday life.
Dr. Nikhil Kapila:
2:36
So the liver serves many functions. It helps detoxify things that you eat. It helps the metabolism of the different medications that you take. It's intimately involved in producing blood clotting factors. If your liver stops working, you cannot clot blood. It is involved in the metabolism of various fats, proteins, is involved in the storage of sugar in the liver. It's involved in the production of bile, as well as excretion, vitamins, mineral storage. And it is very important in maintaining a healthy immune system. If your liver doesn't work, you are immunocompromised.
Dr. Nikhil Kapila:
3:13
Liver disease can present in a variety of different ways the one that we think about, or the one that's a prototypical presentation of somebody who's jaundiced. They look like a yellow highlighter and that's when jaundice happens. Your skin becomes yellow, the whites of your eyes become yellow. But there's other manifestations as well. Some people can develop fluid in the belly, which usually happens much later on in the course of liver disease. People can develop itchy skin, otherwise we call it pruritus. They can develop bruising, usually because they lack those important clotting factors. They can have low blood pressure. They can have pain. They can develop swelling in the legs and the feet. Some people can develop a tremor, especially when they get the confusion associated with liver disease. Weakness, fatigue are other very common symptoms of liver disease and, as I mentioned, also confusion and loss of orientation.
Dr. Michael Koren:
4:01
So just to be clear from my knowledge, does liver disease make your t-shirt turn red, or is that just for dramatic effect?
Dr. Nikhil Kapila:
4:07
I think that's for dramatic effect. Okay, yes, absolutely, and it's a rare case that the liver actually causes pain. Only very few conditions actually cause. Only very few liver conditions actually cause abdominal pain. That's an important clinical point.
Dr. Michael Koren:
4:20
Excellent, so keep on telling us about all these manifestations of liver disease.
Dr. Nikhil Kapila:
4:24
So many of them, right? There's so many different kinds of liver disease. The thing that we think about probably most commonly is alcohol-associated liver disease, and while alcohol is one of the leading causes of liver disease, it's not the leading cause. Actually, this new condition called MASLD or MASH, otherwise known as metabolic dysfunction- associated steatotic liver disease Very long, complex name, otherwise known as fatty liver disease is very rapidly becoming the number one cause of liver disease, not only in the United States but around the world. We also have conditions like primary biliary cholangitis. We have autoimmune hepatitis and Wilson's disease, which are much less common.
Dr. Nikhil Kapila:
5:02
You can develop viral hepatitis, which is hepatitis A, b, C, D and E, and then when people develop chronic liver disease, they can develop liver cancer, which is known as hepatocellular carcinoma. So hepatitis B, hepatitis B is something that is not so common in the United States, don't get me wrong. It's here and it's around, very common though in East Asia. It is caused by the hepatitis B virus, spreads usually through infected blood or bodily fluids. Many people won't experience symptoms until they develop cirrhosis, until their disease has really progressed. However, in the United States, we've also done a really good job of preventing people from getting hepatitis B because we have a robust vaccination strategy and most kids who go to school, college et cetera have been vaccinated for hepatitis B.
Dr. Michael Koren:
5:50
Now you might get to this when you talk about cirrhosis, but at one point hepatitis infectious hepatitis was the number one cause of cirrhosis, but no longer the case.
Dr. Nikhil Kapila:
6:01
That's correct, I mean that's hepatitis C, which was definitely the leading cause of cirrhosis, and we'll talk about that moving forward.
Dr. Michael Koren:
6:08
Here we go.
Dr. Nikhil Kapila:
6:09
Yes, so hep C. Hep C was a killer. At one point of time it was actually one of the worst viruses to get, because in many ways, the treatment strategies for hepatitis C when I was coming through training were really not great. You had interferon and you had ribavirin, which were two medications that were really poorly tolerated and the cure rate was like 30 or 40%. But over the past five or 10 years there's been a tremendous amount of research in the hepatitis C world and they have very effective antiviral agents that cure hepatitis C with an almost 99% cure rate, which is just remarkable. There's no vaccines for hepatitis C, unlike hepatitis B. However, because we now have an excellent medication for the treatment of hepatitis C, the United States there's a USPSTF, which is a preventive services task force basically now recommends that all adults over the age of 18 get tested at least once for hepatitis C. So your primary care doctor should be approaching you about getting tested for hepatitis C, because it's something that is now easy to treat.
Dr. Michael Koren:
7:15
Now we don't have a slide on hepatitis A. Is that something we don't have to worry about?
Dr. Nikhil Kapila:
7:21
It's a great question. Hepatitis A is something that causes an acute viral illness. People can become jaundiced, but hepatitis A does not cause chronic disease. Saying that most Americans should be vaccinated for hepatitis A because in certain cases, especially if you're immunocompromised, hepatitis A can lead to fulminant liver failure. It's not common, but it can happen.
Dr. Michael Koren:
7:42
And, as I understand it, hepatitis A is more likely to come from sort of an oral route, whereas B and C are more from a blood-based route.
Dr. Nikhil Kapila:
7:51
Correct, absolutely. Somebody who goes, you know, eats out and eats at a seafood restaurant, comes back five days later is jaundiced, having fatigue chills you really think about hepatitis A. Or the person who went down to Costa Rica for vacation and comes back jaundiced, that's when you really think about hepatitis A, correct?
Dr. Michael Koren:
8:06
And another question. Sorry to ask too many questions at this point Do we need to worry about hepatitis D? Is that on the horizon?
Dr. Nikhil Kapila:
8:13
That's more obscure. Hepatitis D is only seen in people who are co-infected or super infected with hepatitis B, so I really wouldn't worry about it right now.
Dr. Michael Koren:
8:21
One less thing to worry about, yes, okay, so let's talk about alcohol.
Dr. Nikhil Kapila:
8:31
Yeah, so again, alcohol. You know, we really do think that alcohol is a toxin. Alcohol is definitely poisonous for the liver, there's no doubt about it, and it's caused by excessive alcohol drinking. It can go through various stages of alcoholic-related liver disease. People can just have, you know, bland, you know, elevation of liver enzymes. They can get significant inflammation called alcoholic hepatitis, or you can develop cirrhosis and many people won't have symptoms. You'll go to your primary care doctor, get labs done and they say, hey, your labs are elevated and in many cases it's related to alcohol-related liver disease.
Dr. Michael Koren:
9:01
It's now the real bad stuff.
Dr. Nikhil Kapila:
9:03
Absolutely so.
Dr. Nikhil Kapila:
9:04
This is why we care so much about liver disease, because in the early stages liver disease is preventable or treatable in many ways. Either you can cut out things like alcohol, you can modify your risk factors, you can get treated for viral hepatitis, and our goal is to prevent the development of scar tissue, because when a liver gets replaced by scar tissue you develop a condition called cirrhosis and at that point it's almost like the point of no return. When you develop cirrhosis, your liver really can't heal itself that well, and many people you know. When they develop cirrhosis, that's when you start developing the real nasty complications of liver disease and the complications are related to something called portal hypertension and people can start developing confusion called hepatic encephalopathy. They can start bleeding because of plump, distended blood vessels that form in the esophagus, called esophageal varices, and they can start getting confused in a condition called hepatic encephalopathy and they can get fluid in the belly.
Dr. Nikhil Kapila:
9:58
I may have mentioned that called ascites. The thing is that once you develop cirrhosis and you really can't really get treated so well for your liver disease with medications, oftentimes at that point the only way to get treated is with a liver transplant. So this is the new kid on the block. In a way, it's a new kid on the block.
Dr. Nikhil Kapila:
10:17
That's really an old kid that's just been renamed block in a way, it's a new kid in the block, that's really an old kid that's just been renamed. You know, M-A-S-L-D, otherwise known as MASLD, is what used to be known as NAFLD or NASH, and it was called non-alcoholic fatty liver disease, and now that term has been changed to metabolic dysfunction associated steatotic liver disease. A lot more words, a lot more complicated. Maybe it makes us look a little bit more fancy, I don't know. But really, why they changed the nomenclature was for two reasons. One, a nod to the metabolic syndrome, that we know that the metabolic syndrome is the leading cause of people to develop this particular condition, metabolic syndrome meaning diabetes, high blood pressure, obesity and high cholesterol. And also understanding that very few people do not drink at all, and so therefore the definition of NAFLD, or the previous term, said you cannot drink any alcohol. This condition now incorporates low to moderate amounts of alcohol consumption and go through various stages. So you could see on that schematic very nice, it shows a healthy liver, and when the healthy liver is insulted by the metabolic syndrome, you could start developing fatty liver, and over periods of time, when you have fat in the liver, it leads to an inflammatory response, you get inflammation, and when the liver gets inflamed, you develop this condition called MASH, a metabolic dysfunction associated with steatohepatitis, and over a period of time, inflammation progressive inflammation leads to scarring and scarring leads to cirrhosis.
Dr. Nikhil Kapila:
11:46
So how do you diagnose a patient with metabolic dysfunction associated with steatotic liver disease? First of all, blood tests. Your routine blood work that you get with your primary care doctor may indicate that you may see elevated transaminases, your AST or your ALT. You may see an elevated bilirubin. We also offer fibroscans. Fibroscans have changed the way we diagnose and we stage people with liver disease.
Dr. Nikhil Kapila:
12:12
A fibroscan is a fancy ultrasound. It's taken the place of a liver biopsy, which used to have to be done in many cases, and a fibroscan is a basic ultrasound. Goes on your right upper quadrant, where your liver is, and it tells you how much scarring and how much fat you have in your liver. We can use a basic ultrasound as well to tell us if there's some degree of fat in the liver. We also can use an MRI and use their technology called MR elastography to characterize how much scarring may be in a liver. And in rare cases you need to do a liver biopsy in order to figure out exactly how much. And in clinical studies we sometimes need to use liver biopsy as well to help truly elucidate how much scarring and how much fat is in the liver.
Dr. Michael Koren:
12:54
Out of curiosity. This is an audience question, spontaneous audience question. How many people in the room prior to today have heard of a FibroScan? Show of hands? Okay, this may be a third. How many people in the room have had a FibroScan personally? Okay, it's probably the same people raising their hands twice, which is okay, which is to be expected. As a matter of fact. The reason I bring this up is because one of the things that research brings to the community is better access to this technology, and so, if you are somebody that is concerned and has the risk factors, talk to one of our people and we may be able to get you in for a free fibro scan as part of a screening process for a possible study. No obligation whatsoever, but at least we'll get you some data and get some information about whether or not you could qualify for one of the studies that we're doing to help people prevent liver disease manifestations.
Dr. Nikhil Kapila:
13:46
And just to piggyback on that, you know I mean that's an incredible resource. Fibro scans are not commonly found in the community and have such easy access to one To be able to accurately and objectively characterize the state of your liver. It's a remarkable asset to the community.
Dr. Michael Koren:
14:03
Absolutely, so keep my going. Sorry to interrupt.
Dr. Nikhil Kapila:
14:06
No, no problem at all. So risk factors. Again, it's a metabolic syndrome. It's got its name in the actual disease state, and metabolic syndrome consists of several different disease states, so obesity being the first, the most powerful risk factor for the development of fatty liver disease. The number two is diabetes. Then you also have high blood pressure and you have hyperlipidemia either high triglycerides, low HDL or high LDL. So all of these factors contribute to the development of fatty liver disease. How do you reduce your risk?
Dr. Nikhil Kapila:
14:40
So several different things, and it's been for many years and for decades we've understood that the bedrock of the management of fatty liver disease has been lifestyle interventions diet and exercise. So weight loss about 10% of your weight going into it has been shown. A weight loss of about 10% of your current weight has been shown to have dramatic improvement in people with fatty liver disease. When you take a biopsy of somebody prior to weight loss and you biopsy them after they've lost 10% of their body weight, you see significant improvement in both fat and scarring on that biopsy slide. Eating a healthy diet the Mediterranean diet has been tried and tested to be beneficial in people with fatty liver disease. Exercising is great and avoiding alcohol. But for years we've only talked about lifestyle interventions.
Dr. Nikhil Kapila:
15:35
But now, thanks to the work that ENCORE does and thanks to the work that has been done in the research field, we now have one FDA-approved drug. It's called Resmitron or Resdifera. It is the only currently FDA-approved drug. It's called Resmitrom or Rezdiffra. It is the only currently FDA-approved drug for people who have F2 to F3 scarring. So when you get a FibroScan, a FibroScan will tell you how much scarring you have, on a scale of 0 to 4. 0 being no scarring, 4 being you've developed cirrhosis. So if you're at that stage of F2 to F3, you may qualify for this medication and, amazingly, ENCORE was part of the clinical trials to get Rizdiffra approved.
Dr. Michael Koren:
16:10
Yeah, and I'll tell you this is personally very gratifying to me, not because I'm a liver person, I'm a cardiologist but just to be part of the process that takes disease that had no solution and then get people involved in the community to find the solution, and then working with a company to get the solution through the regulatory process and now having a product in the market is just so reassuring and gratifying.
Dr. Nikhil Kapila:
16:35
So absolutely as a hepatologist who for years has not had a valid or viable option, I mean it's amazing, so it's, I mean yes, it is on all fronts, absolutely.
Dr. Nikhil Kapila:
16:47
But that's not the only drug, you know. There's more drugs that are coming down the pipeline and we at ENCORE are evaluating other drugs that can be used to help in patients with metabolic dysfunction associated steatotic liver disease. While there's different targets of thyroid receptors within the liver, there are other medications now that have other mechanisms of action that can also help, or potentially help, in fatty liver disease, and they can work in a variety of different ways by decreasing the fat in the liver, by lowering your blood sugar, by lowering cholesterol and by increasing insulin sensitivity, because what we realize with fatty liver disease is that there's a real component of insulin resistance, and so that's another mechanism to hit. So hepatocellular carcinoma, HCC. So the number one cause of cancer in the liver is actually metastatic disease, right, the liver. Because of where it sits and its blood supply, it's very vascular. When somebody develops cancer, let's say in the colon or elsewhere in the body, oftentimes you can get, or sometimes you can get a liver met [metastatis], and so that's the number one cancer the liver. But if you talk about primary liver cancer developing de novo from the liver, the number one liver cancer is hepatocellular carcinoma, and in almost all cases. It's very rare. In most cases, hepatocellular carcinoma is preceded by cirrhosis. So most people will have cirrhosis for years and then develop HCC.
Dr. Nikhil Kapila:
18:16
Because what do cancers like? Cancer likes chaos. And what is a fatty liver? What is an inflamed liver? What is cirrhosis? It is a liver in chaos, and so that's where cancer forms, and oftentimes tumors don't cause any symptoms. And here, right now actually as of now, and I'm the primary investigator on this study is that we're actually investigating the use of a blood test to detect cancer at early stages. So in people who have cirrhosis, we're able to do a blood test, and it's obviously in the early stages of investigation right now, but we're trying to see if that can help and detect cancer, as opposed to requiring people to undergo regular imaging studies.
Dr. Michael Koren:
18:57
Yeah, and that's super cool, and I guess there are more and more diseases that are being diagnosed with simple blood tests.
Dr. Nikhil Kapila:
19:03
Correct, so this is kind of part of that trend, absolutely, absolutely, I mean, and you know it's in its earliest stages and we're trying to see whether this is beneficial, whether it works, but absolutely, I mean, whatever helps the patient get to a diagnosis is what we're trying to do.
Dr. Michael Koren:
19:18
And is this study ongoing as we speak?
Dr. Nikhil Kapila:
19:20
Absolutely Correct.
Dr. Nikhil Kapila:
19:21
Correct. We're still recruiting for patients in the study.
Dr. Michael Koren:
19:24
Maybe just a little bit of information. These are people that have an imaging test that get referred, or how does that work?
Dr. Nikhil Kapila:
19:29
No, it's anybody who has got a diagnosis of cirrhosis actually Whoever has a diagnosis of cirrhosis. They get enrolled, they get a blood draw and at the same time they get an ultrasound and then we follow them over the course of one to two years. So primary biliary cholangitis we're entering the more obscure world of liver disease now. It used to be called primary biliary cirrhosis. The name changed in the past about five years or so. It's a chronic autoimmune mediated liver disease that affects the bile ducts, usually seen in women. Symptoms are oftentimes disregarded, the most common symptom being fatigue, usually seen, as I said, in middle-aged women who present with fatigue, itching, maybe jaundice, and currently there's several different medications that we have that we can use. Ursodeoxycholic acid, obeticholic acid and a new class of medication called PPARs have all been shown to improve outcomes in those patients and slow liver damage. So do you qualify for a complementary FibroScan? We actually have some of our staff in the back and they'll be able to talk to you about what FibroScan is and whether or not you qualify and can sign up for one even today. But the people who qualify for it at our center on south side are those who are overweight or obese, high cholesterol, high triglycerides or who have type 2 diabetes.
Dr. Nikhil Kapila:
20:49
So lots of benefits, guys, in participating or partaking in clinical trials. One you're really helping medicine expand. I mean, you're not only helping yourself, you're helping people in this room, you're helping a greater good by making medicine progress and advance. You receive a lot of attention from not only physicians but also from our study staff. You receive a lot of additional monitoring and tests and you truly are a medical hero. There's no doubt about it. So it's interesting that there still remains some degree of hesitation when it comes to clinical trials and in a survey that was done of the general population, less than 50% were actually interested in clinical trials. But in those people who actually enroll in a clinical trial, they enjoy it and 97% of patients who were in one clinical trial say, hey, we'll go to another one. And that just shows you that there's a lot of benefit that is derived from a patient, either from a satisfaction perspective, the extra care perspective, or having access to drugs that are not yet on the market.
Dr. Michael Koren:
21:58
I find this to be an absolutely remarkable statistic. How many products can you think of that? There's a tremendous skepticism before somebody tries it. Then they try it once and they become sold for life?
Dr. Nikhil Kapila:
22:11
All the time.
Dr. Nikhil Kapila:
22:12
Yeah, absolutely.
Dr. Michael Koren:
22:13
It's not a common product, that's like that. So to me this is really reinforcing in terms of what we do on a day-to-day basis. The other thing to your point about sharing information I had a recent lecture tour in Saudi Arabia. I did that about two weeks ago. I actually gave 14 lectures in three cities in Saudi Arabia in six days, so it was a bit of a whirlwind tour before Trump came. They were joking with me that I was getting everything ready for Trump's visit.
Dr. Nikhil Kapila:
22:40
Sure, sure, sure.
Dr. Michael Koren:
22:41
But anyhow, what I found so remarkable was we presented some data of studies that we did here in Jacksonville and they absolutely were spellbound on every detail and so appreciative of the work that we have done in this community and that our patients have done in this community to help educate people in other parts of the world. Yeah, So there's also an element of diplomacy in it, almost that this is our goodwill ambassador type of approach to creating connectivity with other people around the world, that we share information about what we learn about people's health, absolutely. So to me that was really an exciting experience and it gets to this point right here Absolutely,
Announcer:
23:22
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Announcer:
23:24
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