Fatty Liver Disease

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end-to-end. Hi, again everyone, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, president of Maine Campus and colorectal surgeon here at the Cleveland Clinic in beautiful Cleveland, Ohio. And today, I'm very pleased to welcome Dr. Sobia Laique, who's a transplant hepatologist in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic and Chair of the Metabolic Dysfunction-Associated Steatotic Liver Disease Task Force. Dr. Laique, welcome to Butts & Guts.

Sobia Laique: Thank you so much for having me.

Scott Steele: So, we always like to start out with a little bit about you. So, where did you train, where are you from and how did it come to the point that you're here at the clinic?

Sobia Laique: Happy to answer that. So, it's a little bit of a long-winded story, so I'll try to summarize it. But I'm essentially from Pakistan, but I did most of my growing up and training in England, because that's where my father was getting his medical training from. Then had a short stint in Pakistan. And then about 10 years ago, moved to the US for my medical training. And I'm actually a product of the clinic itself. So, I did my residency and my advanced fellowship here and then my GI training at Mayo Clinic. But happy to come back here and it's been phenomenal.

Scott Steele: So, today, we're going to be discussing Metabolic Dysfunction-Associated Steatotic Liver Disease or MASLD. So, to start with, can you break it down to simple terms? What exactly is MASLD and why should people be aware of this condition?

Sobia Laique: Absolutely. So, I completely agree, it is a little bit of a mouthful. So, it's known as MASLD. And essentially, this is just a new terminology for a fairly well-known term known as fatty liver disease or non-alcoholic fatty liver disease. And so, about two years ago, we as a hepatology community decided to change the nomenclature for two particular reasons. One was to help patients better understand that this disease was driven by metabolic dysfunction. Second, to remove the stigmatizing aspect of having the term fatty in it. So, what MASLD essentially at the core of it is, is when a patient has metabolic dysfunction, you start developing pathogenic fat accumulation within the liver and then the subsequent consequences from that.

Scott Steele: Are there different types of this liver disease and how do they differ?

Sobia Laique: Great question again. So, what we know is that fatty liver disease or fat buildup in the liver can be from two, three different causes. So, we came up with the umbrella term of Steatotic Liver Disease, which in layman terms is known as fatty liver disease. And the two major causes of that are, number one, metabolic dysfunction, which is known as MASLD. And the second big reason for fatty liver is alcohol-related liver disease. So, it's important to remember that even the mechanisms to which alcohol causes liver damage is by first excess fat accumulation within the liver cells. So, I'd say those two make up the bulk of the cases that we see.

And then there's a small percentage of rare diseases that can also cause abnormal fat buildup in the liver. Some of these are autoimmune conditions, like celiac disease. Some infections can do that, such as hepatitis C, genetic diseases like Wilson's disease. And the other group that we see are certain medications or what we call drug-induced liver injury. So, steroids, certain anti-inflammatory drugs, certain cancer drugs can also, through a mechanism of drug injury, cause fat buildup in the liver.

Scott Steele: So, you mentioned the fatty liver disease or non-alcoholic fatty liver disease, but on a level of what it's actually doing to the liver, are these the same thing? Is there a difference between the two? How does this all work out?

Sobia Laique: So, I think it's important to remember that fatty liver disease can be through a whole host of things. And then within that, we then have to parse out is this related to metabolic dysfunction, which was previously called non-alcoholic fatty liver disease or is it related to excess alcohol use.

Scott Steele: So, another term that you mentioned is obviously the metabolic dysfunction-associated steatohepatitis or MASH. How does this condition fit into the bigger picture?

Sobia Laique: Initially, what's going to happen is... And to help understand this, you have to understand what the disease trajectory or the natural progression of it is going to be. So, when you have a patient with metabolic dysfunction, which is driven by things like obesity or insulin resistance, diabetes, you will start getting fat accumulation within the liver cells. So, that is simple steatosis or fatty liver. Now, unfortunately, fat or adipose tissue is toxic to the liver cells. So, over time we're going to start seeing inflammation of the liver cells, and then cell injury and cell death. And that is when you start developing MASH or metabolic dysfunction-associated steatohepatitis.

So, initially, there was just fat buildup in the liver. Now the fat is actually causing liver cell damage and cell death. And when this process is left unchecked, you then start progressing to MASH-related fibrosis, which is when as there's more cell injury and cell death happening, the liver is trying to recover or regenerate. But in the process, starts causing activation of a particular group of cells called the hepatic stellate cells, which then start laying down scar tissue or fibrotic tissue within the liver.

Scott Steele: So, does a person who gets fatty liver disease actually have to have morbid obesity or are specific risk factors that make some people more likely to develop it?

Sobia Laique: Great question again. So, it's interesting. With MASLD, what we realize is, is that at the core of it it's driven by metabolic dysfunction. However, the rates of progression of the disease, the severity of the disease are dictated by other things like a patient's genetic risk profile and what we call their epigenetics, which is their lifestyle choices. So, when you have a patient who has metabolic syndrome, we typically see this in patients who either are struggling with being overweight or having obesity for a prolonged period of time.

The other group of patients we see this in who have underlying insulin resistance, such as in women who might have Polycystic Ovarian Syndrome, which unfortunately then leads them down the line to develop type two diabetes. So, the bulk of the patients who develop MASLD will have obesity or type two diabetes driving the disease. And then other metabolic dysfunction parameters, such as high cholesterol, high blood pressure, also further propagate or promote the disease.

Scott Steele: So, are there any early warning signs of MASLD?

Sobia Laique: Unfortunately, in the initial stages of disease, there are actually minimal to no warning signs. And so, oftentimes, the way the disease is actually recognized is if you go in for either routine labs through your primary care and they notice that your liver numbers are elevated, or you have abdominal imaging, like an ultrasound or a CAT scan done for whatever reason, and they identify that there's fat buildup on your liver. And so, unfortunately, because of this reason, we were identifying patients when it was already too late in the disease. Or by the time that they were developing symptoms, they had already progressed to liver cirrhosis. However, the good thing is, I think as we're developing increased awareness of the disease, healthcare providers have become more cognizant of screening for the disease earlier. So, most patients who may have obesity or type two diabetes, their primary care physicians, endocrinologists, are being strongly encouraged now to screen for the disease earlier.

Scott Steele: So, how is MASLD diagnosed? And if I'm a patient listening to this podcast, is there something that I should say, "Hey, listen, I'm worried about my liver and I need to go ask my doctor about it?"

Sobia Laique: Great question. And I think that's such an important part of patient advocacy. So, if you're a patient who has a diagnosis of obesity, type two diabetes, high cholesterol or high blood pressure, you absolutely should be asking your healthcare team to screen you for MASLD. Now, the way to do that is there's typically a step-wise approach. So, the first thing we're going to do is assess your complete metabolic panel, essentially check your liver numbers. And if they are elevated, then we will recommend that you undergo some kind of non-invasive liver testing. And the one that's typically recommended and readily available is having an imaging test done called a FibroScan or vibration-controlled transient elastography. And this is a quick test that we can do in our liver clinic. And what it does for us is it gives us a crude estimation of the amount of fat buildup on the liver, and then also tells us if there's potentially any liver scarring.

Because what we do with the FibroScan is we measure how stiff the liver is, which then correlates to any scar tissue buildup. Now, to supplement that, we do have more sophisticated tests, like certain specialized MRIs, such as an MRI elastography with protein density fat fraction. These are tests that can then accurately quantify for us the percentage of fat buildup and scar tissue in the liver. And then in certain cases, we might recommend a liver biopsy as well. And that might be because there's some diagnostic uncertainty regarding what the severity or extent of your liver disease is or there's concern that there might be something else at play.

Scott Steele: So, how do you treat MASLD? Is it something, lifestyle changes, diet, exercise, or do you need medication or how do you go about this?

Sobia Laique: So, when I talk to patients about management strategies or treatment for MASLD, what I tell them is that you have to go back to the core problem, which is we need to address the metabolic dysfunction. And automatically, we will address the MASLD. So, a lot of our management strategies are actually targeted at optimizing your weight, optimizing your diabetes control, blood pressure and cholesterol. Because what we've seen is that as patients start losing weight and then sustaining that weight loss, the disease starts reversing. And so, usually, the numbers we're coding patients is that if you lose about seven to 10% of your weight, the inflammation in the liver moves down. And then over time the fat starts reversing and hopefully the scar tissue as well.

So, at the core of it, we're really recommending implementation of lifestyle changes, which is you need to optimize your diet and your exercise. And typically, from a diet perspective, we're recommending heart-healthy diet or Mediterranean diet principles. And then from an exercise perspective, we're recommending that they build in, at least based on the CDC guidelines, 150 minutes of moderate to high intensity exercise per week. And whether that's aerobic, whether that's strengthening, whatever suits the patient best. So, that is the foundation. However, we do now have medications that we use to supplement or complement these efforts.

And a lot of these medicines are targeted at weight loss strategies, which will ultimately help reverse the fat buildup and the inflammation. We fortunately enough, were able to get the first FDA-approved medication for MASH with fibrosis in 2024, which is called resmetirom. And so, we now finally have a medication that we can make available to our patients. And the other drugs that are in the pipeline are a lot of the medicines that already are well-known within obesity and diabetes space, such as your GLP-1 agonist. So, there's a lot of data now coming out showing that medicines such as semaglutide, tirzepatide, even liraglutide help reverse the disease and so are being used in a complementary fashion.

Scott Steele: So, let's go the other direction. If MASLD is left untreated, what happens? How serious can it get?

Sobia Laique: I think that's such an important conversation to have, because it really allows patients to take onus of the disease. And so, unfortunately, what we've seen is, is because of the rising rates of obesity and diabetes, 30% of the population now has MASLD. So, that nearly equates to 100 million patients in the United States. And unfortunately, if you don't get control of the disease at an earlier stage, over time it will progress to MASH, subsequently MASH with fibrosis, and then eventually liver cirrhosis, which is then irreversible damage to the liver, at which point we will then start seeing liver function decline. So, our aim of treatment is really to prevent progression to liver cirrhosis.

And then the other complication that we worry about is development of liver cancer. So, MASH with fibrosis is strongly linked to development of liver cancer as well. And so, unfortunately, once a patient progresses to either liver cirrhosis or liver cancer, the ultimate treatment we then can only offer our patients is liver transplantation. And so, that is really the idea behind early screening case identification and management to prevent these life-threatening complications.

Scott Steele: So, you mentioned end-state treatment with surgery being a liver transplant. But short of that, does other surgery play a role in MASLD? Does bariatric surgery, weight loss surgery play a role or any other specific surgical operations for MASLD?

Sobia Laique: Absolutely. So, any intervention that is targeted at weight loss will tremendously help the patient. So, bariatric surgery time and time again has shown significant efficacy in terms of weight loss. And not just losing the weight, but also sustaining that weight loss. And so, with that, you simultaneously also get control of your diabetes, cholesterol and blood pressure, and subsequently reversal of your MASH and liver fibrosis. So, there's extensive data showing that if we offer bariatric surgery or what we call metabolic surgery now to patients at an earlier stage, it will reverse the disease, so much so that we're even now offering it to our patients once they progress to liver cirrhosis.

Scott Steele: So, is MASLD preventable?

Sobia Laique: I would say yes, because ultimately the disease is significantly driven by lifestyle choices. So, if you're making mindful lifestyle choices and following a Mediterranean diet, staying active, abstaining from alcohol, absolutely, the disease is preventable.

Scott Steele: And so, for those who have already been diagnosed, what does daily life look like with MASLD? Is there a cure? You talked about the fact that it is reversible, but can you live just on the edge with it that you never really get all the way back to normal? And is there things that you have to do in terms of long-term management?

Sobia Laique: Absolutely. So, I think for patients who are already diagnosed with MASLD, your daily life really involves, again, making mindful lifestyle choices in terms of dietary adjustments, regular exercise. But then also working with your healthcare team to ensure that you're getting regular checkups, to ensure that you're not developing life-threatening complications from the disease. But then also having conversations regarding what medication options we can offer you, what surgical options we can offer you to hopefully reverse the disease.

Scott Steele: So, looking into the future, are there any new exciting trends or treatments, or advances in research for MASLD? What's on the horizon?

Sobia Laique: I absolutely love this question. So, I think for scientists and clinicians who've worked in this field for the past two to three decades, I would say, it's a really exciting time for the field because there's several promising treatments that are on the horizon. So, the biggest breakthrough we had was with the FDA-accelerated approval of resmetirom in 2024. But then there's a lot of other medication classes, such as the GLP-1 receptor agonist that are showing significant promise in the treatment of MASLD. And there's multiple clinical trials evaluating their efficacy and long-term benefit. There's also different combinations, drug therapies that are coming out, looking at drug classes like FGF21 and 19 as agents to reverse fibrosis. So, a lot of ongoing research in this space. And I think in the next couple of years, we'll see quite a few medications receive FDA approval for treatment.

Scott Steele: That's fantastic. So, now it's time for a quick hitter. It's a chance to get to know you a little bit better. First of all, what is your favorite sport?

Sobia Laique: Oh, tennis.

Scott Steele: What is your favorite food?

Sobia Laique: That's a hard one, but I'm going to say Mexican cuisine wins each time.

Scott Steele: What was your first car?

Sobia Laique: So, my first car was a present from my father, and it was a Tesla.

Scott Steele: Oh, fantastic. That's a good first car. And so, finally, if you had a superhero power that you could garner, what would it be?

Sobia Laique: Being able to read people's minds.

Scott Steele: That's fantastic. And so, do you have a final take-home message for our listeners?

Sobia Laique: So, I think one of the things I try to really empower my patients with is knowledge, because at the end of the day, knowledge is power. And so, I think understanding MASLD and its implications really empowers patients to take charge of their liver health. And I think by adopting a healthy lifestyle, you can significantly reduce your risk of developing the disease, or if you already have it, then managing the disease really well.

Scott Steele: Fantastic advice. And so, to learn more about MASLD or to schedule an appointment for treatment at Cleveland Clinic, please call the Digestive Diseases, 216.444.700. That's 216.444.7000. You can also visit our website at clevelandclinic.org/digestive. That's clevelandclinic.org/digestive. Dr. Laique, thanks so much for joining us on Butts & Guts.

Sobia Laique: Thank you.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.