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🎙 Are You at Risk of Fatty Liver Disease Ep 234

• Dr. Nikhil Kapila • Episode 234

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What if we told you that your liver plays a more critical role in your health than you ever imagined? This episode of MedEvidence promises to uncover the essential functions of the liver, from detoxification to immune support, and explain why maintaining liver health is pivotal. Dr. Nikhil Kapila dissects the complexities of fatty liver disease, now rebranded as metabolic dysfunction-associated steatotic liver disease (MASLD), and its alarming connections to metabolic disorders such as obesity, diabetes, and high cholesterol. We'll also explore the broader spectrum of liver diseases, including alcohol-related liver disease, viral hepatitis, and rare conditions like primary biliary cholangitis and autoimmune hepatitis. Get ready to learn about groundbreaking treatments and gain insight into the rising prevalence of MASLD as a leading cause of liver disease and liver transplantation.

Three Key Takeaways:

  • Understanding Fatty Liver Disease
  • Clinical Trials for Fatty Liver Disease
  • Q&A from the public

Recording Date: August 15, 2024

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Music: Storyblocks - Corporate Inspired

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Announcer:

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts.

Dr. Nikhil Kapila:

Hi guys, Nikhil Kapila so let's get down into our talk. So, guys, today the topic of discussion is going to be are you at risk for fatty liver disease? And thank you to ENCORE and Borland Groover for giving me the opportunity to speak to you guys as a patient population and educate you all on fatty liver disease. So you know, today my objectives are to talk about the importance of liver health and where the liver, you know, sits in your overall body's maintenance and homeostasis, and just how critical the liver is. We're going to talk about what indeed fatty liver is and how the nomenclature actually has evolved over the past couple of years, talk about current treatments which are available in the world of fatty liver disease, talk about the research opportunities that us at Borland Grber and Encore have to offer our patients, and talk about ways that you, as patients or as advocates for your family members or friends, can get involved in patient care for the management of fatty liver disease.

Dr. Nikhil Kapila:

So what does the liver do? So the liver is an essential organ. Without a liver, you cannot live. Other organs, for example, such as the heart, have pumps, you have dialysis for kidneys, you have ventilators for lungs. There's no such device for the liver. So the liver is an essential organ in every possible way, and it serves a variety of functions in the body. You know, the liver works to detoxify the blood, meaning that anything that you eat medications, anything you really consume is somehow usually metabolized or processed within the liver. The liver is responsible for creating clotting factors, and so, therefore, when patients develop end-stage liver disease, their clotting factors are impaired and they're more likely to bleed. The liver is responsible for the metabolism or the breakdown, as well as the production of a variety of different essential proteins and fats. The liver is intrinsically involved in the management and the balance of your sugar control, and therefore, when a liver stops working acutely, that's why patients may see a decrease in their glucose. It's responsible for bile production and excretion. The liver produces bile and it drains it into the intestine, and so, therefore, when there are issues with the liver, people may become jaundiced, and that's due to an increase in bilirubin or bile within the blood.

Dr. Nikhil Kapila:

It's responsible for vitamin and mineral storage. The liver is responsible for producing vitamins, for storing vitamins, for metabolizing vitamins. When patients develop liver disease, they oftentimes are deficient in many of these vitamins and also it's very important in your overall immune response and it's supporting your immune system. Patients who have liver disease are immunocompromised. Patients who have cirrhosis are indeed quite immunocompromised, and that's just important to keep in mind as patients, as well as for us as physicians. So in terms of common liver diseases, the world of liver disease has evolved tremendously over the past several decades.

Dr. Nikhil Kapila:

Alcohol-related liver disease remains one of the leading causes of liver disease around the world and in the United States, fatty liver disease has changed its name. It used to be called non-alcoholic fatty liver disease, but that name has changed. It was confusing To some, it was stigmatizing and it did not really encompass the entire range of liver disease that really falls underneath that quote-unquote term. So recently, experts from around the world decided to change the name to a different nomenclature and now it is called metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction because the development of this particular type of liver disease is directly connected with metabolic disease, namely high blood pressure, high cholesterol, diabetes or elevated glucose and obesity. Now, within this range of metabolic dysfunction associated steatotic liver disease, there's a broad range of presentations, and one of those that is very important from our perspective is something called metabolic dysfunction associated steatohepatitis. So steatotic means fat, hepatitis means inflammation within the liver, and so therefore, that is one subtype which is critical in terms of the overall management of metabolic dysfunction associated liver disease.

Dr. Nikhil Kapila:

And then you have viral hepatitis, things like hepatitis B and hepatitis C. Then you have other more obscure liver diseases, such as primary biliary cholangitis, things like hepatitis B and hepatitis C. Then you have other more obscure liver diseases, such as primary biliary cholangitis, autoimmune hepatitis, wilson's disease, but, for sake of discussion, those are less common liver diseases compared to the big three. In terms of viral hepatitis, actually, we have, you know, over the past 10, 15, 20 years, we now have actually seen a cure for hepatitis C. It's a highly effective medication that is taken by mouth, and really the numbers of hepatitis C have decreased tremendously. In its place, we've seen a tremendous rise in metabolic dysfunction associated steatotic liver disease, and that is global. It's not just the United States. We are seeing that globally. It's rapidly becoming the number one cause of liver disease, as well as quickly becoming one of the leading causes, one of the leading reasons for liver transplantation, not only in the United States but around the world.

Dr. Nikhil Kapila:

So what indeed is metabolic dysfunction associated steatotic liver disease? I think, for my own sake because I'm going to go into a word jumble every time I say that we'll just call it MASLD. So everybody's born or most people, the vast majority of people are born with a healthy liver, and over a period of time, over many years we as human beings insult our liver in many different ways. The main risk factors for MASLD, however, are obesity, diabetes and elevated cholesterol or dyslipidemia. And so from a healthy liver, people start developing fat deposition, and when fat gets a positive liver over the course of many years, they can start developing inflammatory changes. And so when people start developing inflammatory changes and that inflammation persists and is not in any way stopped or improved, people then start developing scar tissue within the liver. And when the liver gets replaced by scar tissue, then you have developed a condition called cirrhosis.

Dr. Nikhil Kapila:

And when you develop cirrhosis, you then are susceptible to the complications of cirrhosis, which are many. One of them is the development of liver cancer, but the other ones are things like ascites, the development of fluid in the belly or confusion, something otherwise known as hepatic encephalopathy, or bleeding from blood vessels within the esophagus, known as variceal bleeding, and when patients develop cirrhosis that's usually irreversible. You see, before you develop cirrhosis the liver goes and progresses to multiple different stages of scarring. And during those various stages of scarring, if we as providers and as patients are able to recognize and stop that progression by taking away or improving the precipitating factors, you can actually retard the progression of fibrosis and not develop cirrhosis. But when you do develop cirrhosis, that in many ways is a irreversible point of no return. And when somebody develops cirrhosis, some people can live with cirrhosis without complications. But the only way to really cure cirrhosis is with liver transplantation.

Dr. Nikhil Kapila:

So how do we diagnose MASLD? So there's a variety of different tools that we have in our diagnostic toolbox to help us diagnose patients with liver disease. So the first thing is blood tests. The blood tests that we commonly look at are transaminases, which include your AST and your ALT. Those are markers of inflammation and those are generally the first numbers to rise in patients who have fatty liver disease. And those numbers can range from just over the upper range of normal to many times the upper range of normal. And what is indeed normal is actually a point of contention, a point of debate In my mind. As a hepatologist, I like to see my ALT and AST less than 30. In some labs that you may go to, they actually may say the upper limit of normal is 50 or 60, and I believe that is not the case. The lower that, the closer that number is below 30, the better off you are from a liver perspective.

Dr. Nikhil Kapila:

Now, when patient liver disease progresses and they start developing significant scar tissue, that's when you see other numbers in that liver panel go up, and namely, the other number that we really look at is bilirubin. Bilirubin is a marker, a true marker of liver dysfunction, and when that starts going up, that's really when we need to start getting concerned about liver disease progression. And indeed, when your bilirubin goes up, that's when patients become jaundiced. There are other numbers that we may look at, especially when people have progressed to a more advanced perspective. We'll look at INR, which is another name for international normalized ratio, which measures how well your liver is producing clotting factors. We may look at sodium. We may look at your creatinine as surrogates or markers of kidney function, but that's usually when you develop cirrhosis.

Dr. Nikhil Kapila:

We then have non-invasive tools for trying to determine how much scarring or fat one has in their liver. Back 20 years ago these tests didn't really exist and we really had to rely on liver biopsy. But now we have different tools that use ultrasonographic technology to help determine in a non-invasive way how much scarring or fat one may have, and that tool is Fibro-scan scan. It's a very effective tool, it's reproducible and it really gives the provider an excellent idea of where indeed a patient is in that progression of liver disease. Ultrasounds can be used as adjunct tools, especially to help determine as an initial screening tool to see if there is an abnormality within the echo texture within the liver, and it's usually a test that when you see your primary care doctor they may see abnormal liver tests and they may then reflex to a liver ultrasound MRI is a very valuable tool and it's amazing that at Borland Groover we actually have access to MR elastography technology at our Southside campus, because where I came from, at Cleveland Clinic, we actually did not have the technology. And that's cutting-edge technology and that's using magnetic resonance imaging to really hone down on the degree of scarring and fat one has in their liver and the gold standard been around for years, decades. That is invasive, may be associated with pain, may have some complications, but really in many ways when it is done, it's because it's absolutely necessary from a diagnosis or a staging perspective is a liver biopsy.

Dr. Nikhil Kapila:

So what are the risk factors for metabolic dysfunction associated steatotic liver disease? The number one risk factor is obesity. So obesity, namely central adiposity, so when there's increased girth around the waistline, that's going to be your number one risk factor. But there are other very important risk factors, namely high blood sugar or diabetes associated with insulin resistance. Other risk factors include hypertension and dyslipidemia. Dyslipidemia, meaning either high triglycerides, low HDL or high LDL cholesterol.

Dr. Nikhil Kapila:

So what are lifestyle changes that one can do to reduce your risk of developing fatty liver disease? So the first thing is weight loss and actually I tell my patients this quite frequently that the real target that we're really trying to hit on is 10 of your current body weight. That's the initial target. So if somebody weighs 250 pounds, weight loss reduction of about 25 pounds. You see, because there have been studies that have been done that was initially done about almost about 20 years ago now and has been reproduced over time, with patients who have fatty liver disease who present to their physician, who undergo a liver biopsy, who then are able to lose up to 10% of their body weight. You can actually see significant improvement, if not resolution, of scarring and fat on that liver biopsy. So that's remarkable. But how do you lose weight?

Dr. Nikhil Kapila:

You lose weight by a combination of diet and exercise, diet being the number one, most important thing, and the diet that has been studied time and time again in this particular disease state is a Mediterranean diet. You can Google what the Mediterranean diet is, but really it centers around eating lean meat, mainly chicken or fish. Avoiding sorry, eating fresh vegetables, avoiding using, avoiding fried foods, avoiding red meat, eating basically fresh, unprocessed foods. It's not easy to maintain mediterranean diet. It's not cheap, necessarily either, but there are ways to make it work in a personalized fashion. And then there's exercise.

Dr. Nikhil Kapila:

Exercise is another key component, not only for for liver health, but also just for overall longevity, for overall quality of life, and the recommendation is 150 minutes per week of moderate intensity exercise. Moderate intensity exercise varies from person to person, but usually it's a brisk walk where you get your heart rate up, you break into a little bit of a sweat and that's really what you're trying to do, and the other component to this is alcohol avoidance. The theory that one or two glasses of red wine at night is healthy and good for you has been debunked of recent and really there's no healthy amount of alcohol. And when somebody has liver disease, alcohol consumption should be zero in my book. And again, that's a personalized decision based on the amount of scarring, the amount of fat somebody has in their liver. But all alcohol will do is make a situation worse.

Dr. Nikhil Kapila:

The other thing that's not on here actually that has been recommended and that has been studied over the past couple of years is coffee consumption. That actually drinking one to two cups of caffeinated black coffee every day has been shown to be liver protective, shown to help in patients with fatty liver disease. Has actually been shown to help in all stratospheres of liver disease. Has been shown to be helpful why, it's not exactly known. But one to two cups of caffeinated coffee and, granted, if you go to Starbucks and order a Frappe Macchiato or one of those drinks with whipped cream and stuff, that is negating every positive effect. So it's black coffee which is shown to be effective.

Dr. Nikhil Kapila:

So for many, many years us as hepatologists and gastroenterologists had very limited options to offer our patients for for the management of fatty liver disease. It was namely the previous slide weight loss interventions, diet, you know, some people use vitamin e, some people talked about using other drugs, but really they were quite um, they weren't as effective. And so recently there's been a new drug Its trade name is Rezdiffra, chemical name is Resmetirom which really acts on the thyroid receptors within the liver and is directed towards is liver selective. They've actually been shown to be quite effective in patients with moderate-stage scarring. So those patients who, on a scale of zero to four, effective in patients with moderate-stage scarring, so those patients who, on a scale of 0 to 4 of scarring 0 being no scarring at all, 4 being cirrhosis somewhere in that intermediate range, either a 2 or a 3.

Dr. Nikhil Kapila:

And indeed the world of fatty liver disease is a silent epidemic. There have been many studies that have been shown that there are many asymptomatic patients walking around with metabolic risk factors who have undiagnosed MASLD, and this just highlights and reemphasizes the importance of the world of investigational pharmacotherapy and other treatments for these patients, pharmacotherapy and other treatments for these patients. And that is where us ENCORE and Borland Groover come in and that's where the FDA is really trying to accelerate the approval of certain medications in this particular realm. So at Borland Groover we're currently enrolling patients in several clinical trials. The new medications that are under investigation work in many different ways and some of them work to decrease fat deposition within the liver. Some of them work to modify risk factors, so lowering blood sugar, which, as we know, is a prime risk factor for the development of fatty liver disease. Improving dyslipidemia, prime risk factor for the development of fatty liver disease. Improving dyslipidemia. And also increasing insulin sensitivity, because we know that insulin resistance is again one of the key pathophysiological factors behind the development of fatty liver disease.

Dr. Nikhil Kapila:

So many of you are, you know, never been exposed to a research environment or understand or you know have been in that situation. But there are many benefits to actually participating in clinical trials. One you have the potential to access novel treatments that are not currently available to the public. Not currently available to the public. You get access to Borland-Groover physician investigators like myself and other colleagues of mine who have an interest in this particular disease state and are thought leaders in these particular disease states.

Dr. Nikhil Kapila:

There's no cost for clinical trial testing medications or trial visits. That is covered by as part of the agreement with Borland Groover and the different pharmaceutical companies. Those costs are covered. Generally speaking, a stipend is paid for your time and travel to the study visits and really when you do join a clinical trial you are taking an active role in improving your health and you have the opportunity to change the way we practice medicine, and not only for yourself but for other generations, for your kids, your grandkids, friends, family members, to really make an impact in terms of medical knowledge and medical technology moving forward. So I mentioned FibroScan on an earlier slide. At Borland-Groover we do offer complementary FibroScans to certain patients who have risk factors for the development of fatty liver disease. So those are patients who are overweight, those patients who have dyslipidemia or elevated cholesterol and those patients who have type 2 diabetes.

Announcer:

For four to five years my ALT and AST were above the normal range. The blood work is done twice a year. The last two went down and they are now in the normal range. Does this mean liver improvement? My last bilirubin had increased slightly.

Dr. Nikhil Kapila:

So when we talk about liver disease and we talk about watching liver labs, the most important thing over time is trends. We love watching trends and seeing where things go, the fact that your ALT and ASD got better. Those are markers of inflammation, so you're doing something right in all likelihood for those liver numbers to show some signs of improvement. The best way, though, in my practice what I do is I do do fiber scans on a semi-regular basis, usually every year, to really objectively assess whether or not the scarring and whether or not the fat is actually improving within the liver, because those are the true markers ASA and ALT. They can fluctuate somewhat, but you really want objective markers of scarring and inflammation, and that's in sense of fibro scan.

Dr. Nikhil Kapila:

You know the fact that your bilirubin went up slightly. You know that's something that will need to be trended over time. You know understanding is it your direct bilirubin? Is your indirect bilirubin? There's two. When you, when you look at total bilirubin, you fraction it between direct and indirect, and those will be important things to know. But that needs to be taken into context with what your labs look like and what your imaging looks like.

Announcer:

My sisters and I all have MASLD and high triglycerides. What is the difference with calling it MASH or MASLD?

Dr. Nikhil Kapila:

So MASLD encompasses the entire spectrum, ranging from bland fatty liver so just fat deposition within the liver. Patients have normal liver chemistries. Oftentimes they will have just fat within the liver. If you do a biopsy with no inflammation and no scarring, but when patients develop that subtype of M-A-S-L-D called MASH or metabolic dysfunction associated steatohepatitis, you have entered a new disease state. That is where you have active inflammation, you have scarring which is developing as a result of the inflammation and that is really a disease process that we want to stop it in its tracks and try to reverse. So MASH is a distinct entity within this overall picture of this umbrella of metabolic liver diseases and it's something that we as hepatologists really look at and you really want to diagnose early so you can stop it. Because when you start developing MASH and you start developing that active steatohepatitis or fat inflammation, that is where you start seeing the progression of liver disease. So great question.

Announcer:

My ferritin levels increase with ALT and AST levels. How are these connected?

Dr. Nikhil Kapila:

So ferritin, by by definition, is a protein which is a marker of iron stores. So ferritin is decreased when patients are iron deficient and can be increased in certain states of iron overload. But also it's an acute phase reactant, meaning it can be elevated in patients with an inflammatory state, patients with an inflammatory state. So when the ferritin is elevated in the setting of certain liver diseases, that can be a marker of inflammation within the liver. We don't really follow ferritin levels over time when we talk about fatty liver disease, but it can be a marker of ongoing inflammation.

Announcer:

I was told I have NASH. I am overweight, not obese. I do not drink alcohol and do not smoke. I do not have diabetes. However, my ferritin, ast and ALT are always elevated.

Dr. Nikhil Kapila:

You know, you don't need to only be obese to develop fatty liver disease. There are other metabolic risk factors, such as diabetes. There's insulin resistance, there is some degree of genetic predisposition to certain patients, so there's multiple different risk factors for the development of fatty liver disease. At the same time, if you don't have any obvious risk factors and you have persistently elevated liver tests, there may be a role for further testing to rule out other liver diseases. A liver biopsy may be required in certain situations to come up with a diagnosis. But again, this needs to be done in a personalized, individualized fashion.

Announcer:

My CT scan shows a 0.6 centimeter fat density mass at the dome of the right lobe of my liver, likely related to a small lipoma. Does this have anything to do with liver disease?

Dr. Nikhil Kapila:

You need to talk to the doctor who ordered that CAT scan and follow up with the provider for that. Generally speaking, the lipoma is not associated with fatty liver disease, but any liver lesions need to be closely monitored over time until somebody tells you, hey, nothing else needs to be done about it.

Announcer:

Last January I had a fibro scan of 9.6 and added kefir, kale and blueberry drinks a few times a week. In March this year I had another fibro scan and it went down to 4.3. My weight has gone up a bit. I read on the NIH site that there is a relationship between the gut and the liver and that kefir adds good bacteria. What are your thoughts?

Dr. Nikhil Kapila:

So a hot topic in the world of gastroenterology and in disease states in itself is a role of the microbiome, so that's your bacteria within your gut, in the role of not only liver disease, heart disease, a variety of different disease states. But there is no firm data to start really saying that yes, this diet changes your bacteria and is good for your liver. There are associations, there are thought processes and obviously you're doing something right. If your fiber scan showed objective improvement from 9.6 to 4.3. Not sure. If you're a diabetic and you had an improvement in your hemoglobin A1c, maybe there's an improvement in your cholesterol because obviously and we know that it's not only weight there's a variety of factors that go into the progression or regression of scarring and fat within one's liver.

Announcer:

I am type 2 diabetic. A1c is 6.5. I weigh 115 pounds and my gallbladder was removed eight years ago. I also have high triglycerides. Do you recommend a FibroScan for me?

Dr. Nikhil Kapila:

Absolutely. You have risk factors for fatty liver disease. I would get a FibroScan. You would likely qualify for the complimentary scan at Borland Groover. I think it's a valuable piece of information to have.

Announcer:

I drink an Ayurvedic tea that supports liver, spleen and gallbladder health. It helps me feel better in my gut. Is it a good thing to keep doing?

Dr. Nikhil Kapila:

So you know I am not a homeopathic physician and I think actually that's one of the shortcomings of being an allopathic physician is that we are not very familiar or comfortable with herbal remedies and other formulations. You need to be mindful that there's a whole industry of people out there selling gut or liver cleansing items. In my experience they don't work. Everybody's different and that's a personal decision to make. That's an unregulated industry oftentimes where in my previous career as a transplant hepatologist, we actually saw patients develop significant liver injury from from from over-the-counter or herbal remedies that they bought online from Amazon or other places. So just something to be mindful about. If you feel well, you're doing well on it, then great. But just something to keep in mind that, generally speaking, herbal teas and herbal supplements you need to be very cautious and mindful about them.

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