In Episode 54, Dr. Sarkar welcomes Dr. Jamie Hamilton, who will be talking with us about diabetes and metabolic dysfunction associated stenotic liver disease or MASLD. Dr. Hamilton is an associate professor of medicine in the division of gastroenterology and hepatology. He is the interim director of gastroenterology and hepatology and the director of hepatology for Johns Hopkins Medicine. Dr. Hamilton’s clinical specialties include Wilson’s Disease, cystic fibrosis related liver disease, liver transplantation, hepatocellular carcinoma, cirrhosis. Portal hypertension, acute and chronic viral non-alcoholic fatty liver disease, autoimmune,and cholestatic liver disease.  Dr. Hamilton is a recipient of the National Institutes of Health National Research Scholar Award for gastroenterology and hepatology.

Sudipah Sarkar: [00:00:00] Welcome to Diabetes Deconstructed, a podcast for people interested in learning more about diabetes. I’m your host, Dr. Sudi Sarkar at Johns Hopkins. we developed this podcast as a companion to our Patient Guide to Diabetes website. If you want a trusted and easy to understand resource for diabetes or to listen to previous podcasts, please visit hopkins diabetes info.org.

Today we’re excited to welcome Dr. Jamie Hamilton, who will be talking with us about diabetes and metabolic dysfunction associated stenotic liver disease or MASLD. Dr. Hamilton is an associate professor of medicine in the division of gastroenterology and hepatology. He is the interim director of gastroenterology and hepatology and the director of hepatology for Johns Hopkins Medicine.

Dr. Hamilton’s clinical specialties include Wilson’s Disease, cystic fibrosis related liver disease, liver transplantation, hepatocellular carcinoma, cirrhosis. Portal hypertension, acute and chronic viral non-alcoholic fatty liver disease, autoimmune, [00:01:00] and cholestatic liver disease. His research interests include copper homeostasis and its regulation of lipid metabolism and liver injury, fundamental mechanisms regulating liver fibrosis and the molecular genetics of hepatocellular carcinoma in early detection Biomarkers.

Dr. Hamilton is a recipient of the National Institutes of Health National Research Scholar Award for gastroenterology and hepatology. Welcome, Dr. Hamilton.

Jamie Hamilton: Thank you Dr. Sarkar.

Sudipah Sarkar: One question that we wanted to start off with today is, what exactly is metabolic dysfunction associated ketotic liver disease or MASLD? And could you tell us a little bit about what the name used to be and how did that shift and how does it better reflect how we understand the disease?

Jamie Hamilton: The disease used to be called “non-alcoholic fatty liver disease”. That was considered not to be a great name because it was a diagnosis of exclusion and many people didn’t really pay attention to the diagnosis because they just said the liver enzymes are mildly elevated [00:02:00] and it’s not that big of a deal. The reason for the name change was to really understand who was at risk for this disease, then make a diagnosis of the disease, and then who is at risk for developing serious liver problems from the disease? So there are five criteria, metabolic criteria that we use to determine who is at risk for the disease. And that’s having a obesity or overweight, so A BMI in Caucasians of over 25, and then E East Asians of over 23.

Or an an increased waist circumference of over 90 centimeters in men or 80 in women. Having a high triglyceride count over 150, having a low HDL less than 40, or on medicines to control lipids having high blood pressure or on medicines to control blood pressure or having most importantly type two diabetes and insulin resistance.

So people who have those problems are at risk for having fat in their liver. And we don’t like to use the word fatty liver ’cause fatty is not really a nice word. So we call it steatosis or st thetic liver. And that’s just a [00:03:00] doctor word for fat in the liver. There’s three main reasons why people get fat in the liver.

First one is alcohol. Second one are these metabolic problems. And then the third one. Is much more uncommon. It can be genetically caused or from medicines. But the main reason was take away the stigma of the word “fatty.” Take away the word “non-alcoholic” and really be more inclusive by saying, these are these in really important metabolic problems. Those people with those metabolic problems are at risk for having fat in their liver.

Sudipah Sarkar: Thank you. That’s very helpful. This is a podcast about diabetes and I know a lot of our listeners will be asking which comes first, is it that someone has diabetes and then they develop MASLD? Or do people usually have MASLD and then develop diabetes?

Jamie Hamilton: Usually they develop concomitantly or at the same time, usually at the time of a diagnosis of type two diabetes, the person, a patient will have some fat in their liver. It’s not as though it’s pretty, it would be pretty uncommon for someone to have fatty liver [00:04:00] first or steato liver first and then be diagnosed with diabetes later. But it is possible.

But they’re very tightly linked because. People who have type two diabetes have resistance to the insulin that they’re making, as and among other hormone problems they get. With this insulin resistance, you end up storing fat. In the liver inappropriately, and that’s what leads to the fatty liver.

And you mobilize fat from the your adipose tissues that goes to the liver. And then your liver continues to make its own fat and not checking that you or stopping that in the presence of having fat in the liver, but it can continues to make its own fat. And then of course you get fat from the diet.

Sudipah Sarkar: Another question that many listeners might have is how do you detect maced or how can a patient or their provider find out if they have MASLD?

Jamie Hamilton: The first thing obviously is just a routine checkup with either your diabetes specialist or primary care physician in which liver enzymes can be checked.

And they could be elevated, but that really shouldn’t be the [00:05:00] only test that are is done. There’re an ultrasound of the liver, which is a very non-invasive, easy test to be done should be done to measure fat in the liver. And so what is recommended now is someone who has these risk factors should be screened for fat in the liver, with liver enzymes and with an ultrasound.

And then there’s another simple test that you can use with existing blood tests. It’s called A Fib four, and it stands for Fibrosis four. And the four labs that we use or values that we use are the A ST, the A LT, which are liver enzymes, the platelet count, which is part of the complete blood count, and then the patient’s age.

And you put those numbers into a formula and it can put out a number. If that number is greater than 1.3, then the person could potentially have scar tissue in the liver. And if it’s greater than 2.6, the person, the patient likely has scar tissue in the liver and that should prompt further investigation as well.

So looking for fibrosis is really the most important thing in these [00:06:00] when you make these diagnoses, because that’s what really leads to liver damage is fibrosis in the liver.

Sudipah Sarkar: Based on the FIB four score, what further imaging tests could a general practitioner or endocrinologist order especially if it if it’s exceeds one of the cutoffs.

Jamie Hamilton: So what we generally recommend is something, there’s a thing called a FibroScan, which is an another non-invasive test. It requires a patient fasts for four hours prior to the exam, and then they put a probe on the abdomen over the liver and it measures the amount of fat in the liver and it measures the stiffness of the liver.

And from that, we can determine if there is scar tissue or not. There’s no IV needed. There’s no dye, there’s no biopsy needed in that situation. It’s it’s pretty non-invasive. There’s also a blood test called ELF or Elevated liver fibrosis, which is available at most commercial laboratories.

And that’s a really good blood test too, that can be used to estimate fibrosis. We don’t generally recommend something called the Nash fibro [00:07:00] brochure. That test is is pretty unreliable. And we don’t recommend that.

Sudipah Sarkar: At what point would you say that a patient should be referred to a liver specialist,

Jamie Hamilton: Anybody who has suspected fat in their liver and fibrosis.

Now, of course, if the problem is this is. This liver disease is the most common in the world, and about 30% of Americans probably have fat in their liver. So we can’t see all of them. So we do try and limit our evaluations to those who are just suspected to have fibrosis. One thing I will say too is patients that fib four test is not very reliable.

Once a patient gets over 65 or so. Then it starts to overestimate fibrosis. And so that can be more tricky. And in those patients you might want to go directly to a FibroScan to assess for fibrosis.

Sudipah Sarkar: In terms of treatment, what are treatments that are recommended to treat MASLD ?

Jamie Hamilton: The first thing we always recommend is trying to improve your metabolic risk factors and that we do that through dieting and exercise [00:08:00] because we know that weight loss can improve this condition markedly.

So we recommend generally what’s called a Mediterranean style diet, which is of course, rich in fruits and vegetables and lean proteins such as fish and chicken, and avoiding things like high carbohydrate diets, high fat containing diets, fatty meats like steak, And really portion control as many of your diabetic patients are aware of.

We also ask people to really reduce or avoid alcohol entirely because there really is no amount of alcohol that is safe for the liver. And then we also recommend routine exercise. Trying to exercise 30 minutes, five days a week, 30 days, 30 minutes a day, five days a week. Is ideal. If you do more than that’s even better.

And we studies have shown that if patients engage in that type of activity and are able to lose weight they do improve their metabolic risk factors and then they approve their fatty liver. But when someone has fibrosis, it’s a little bit more serious. And so in that case, there is one medicine that is [00:09:00] approved for this condition and it’s called Remeron.

And it was approved in March of 2024. And and it’s only approved in patients who have fat in their liver and stage two to three fibrosis. And so we determine that through a FibroScan. You can also do a liver biopsy In general, I don’t do liver biopsies for this condition too much unless there’s a competing diagnosis. And there’s also something called an MRI Elastography, which can also measure liver fibrosis, but of course that’s a more expensive test. But this drug rasmaderon. It was shown after a one the clinical trial was about one year long, and they enrolled patients many of whom had diabetes but all of whom had.

Fat in their liver in stage two to three fibrosis, and about 30% of patients at the end of that first year had a full one stage reduction or more in their liver fibrosis and in resolution of their steato hepatitis or their fatty liver. That is what we do for patients who have fibrosis.

I will say that really any strategy to reduce weight improves fatty liver. So many of the drugs that are used now [00:10:00] in diabetes also have the benefit of weight loss. So drugs like Mounjaro or ozempic or other types of what we call GLP one analogs they tend to help people lose weight and their fatty liver often improves.

And there been recently some clinical trials showing. Real benefit in patients with fatty liver disease and fibrosis in particular manjaro. Tirzepatide. It was published in the New England Journal of Medicine, a phase three trial showing about 50% of patients had a one or more stage reduction in their scar tissue.

So that’s an emerging indication for this condition, this fatty liver disease. But it’s not yet FDA approved it’s not a standalone drug just for this condition. Some people who have very significant obesity will also benefit from bariatric procedures. And in those patients, their metabolic risk factors rapidly improve after weight loss from those conditions.

So that’s always something to consider too. So things like endoscopic sleeve gastrectomy or surgical sleeve gastrectomy or gastric bypass can be of use.

Sudipah Sarkar: [00:11:00] Are there any exciting avenues of research and innovation that you could share with us in the field of MASLD and metabolic disease?

Jamie Hamilton: I think that the pharmaceutical industry is extraordinarily excited about this condition just because it really affects a third of the world’s population. So there’s something like 75 clinical trials that are ongoing right now at various different stages of development. And and all of these have very exciting preclinical data and e even some small, clinical trials showing benefit.

That’s really the major area of research is actually getting to the patient soon. Is are all these different meds that affect the way the liver handles fat and reduces inflammation and reduces fibrosis.

Sudipah Sarkar: In your experience, what would a coordinated care model look like for someone who has both MA and diabetes?

Jamie Hamilton: So I think a nice coordinated care model would be a team, a team that includes a liver specialist, an endocrine diabetes specialist and perhaps someone who specializes in medical weight loss [00:12:00] therapies. And sometimes in some cases, patient someone that specializes in lipid control lipid medicine sorry, lipid lowering therapies.

And sometimes that can be just a really good primary care doctor. And sometimes some cases it can be a specialist. But those are usually the general people that would be involved.

Sudipah Sarkar: Are there any over the counter medications that are used for treatment of MASLD?

Jamie Hamilton: I would not necessarily recommend over the counter supplements for the treatment of this condition. There are a lot of nutraceuticals or remedies that are out there in the lay media and in and in your health store that have been. Touted to help fatty liver disease. None of those have really been rigorously studied and have shown no benefits that we know of.

So I would be really cautious about using any of those. And many herbal preparations or holistic therapies can actually be liver toxic. So I would caution people against using those without the advice of a healthcare professional.

Sudipah Sarkar: Dr. Hamilton, are there any symptoms that a patient with diabetes [00:13:00] might see if they have MASLD.

Jamie Hamilton: That’s a really good question. So unfortunately, when maed in its early stages, it’s really asymptomatic.

You may have mild elevations of the liver enzymes. You may have some abdominal pain in the right side, that’s just vague and hard to describe. But in general, it doesn’t really cause a lot of symptoms. Unfortunately, by the time that. Liver disease really progresses towards cirrhosis.

You can have symptoms and that can be fatigue. It can be yellowing of the skin, it can be swelling of the legs. You can have bleeding problems, you can have confusion, but we really want to find people and treat people well before that happens.

So the answer to the question in the beginning stages, there’s really no symptoms. But as the disease progresses, it can have a lot of different symptoms and much of which can be vague. But fatigue, itching, yellowing of the skin would be really big things of concern.

Sudipah Sarkar: What complications is associated with both liver complications and heart complications.

Jamie Hamilton: [00:14:00] So the the most important liver complication is, is cirrhosis which is a scarring of the liver that can lead to liver failure and it can lead to liver cancer. So MASLD d is the second leading cause of liver transplantation in United States and North and and Western Europe. Oh. And it’s a fire alarm. The and then the heart complications of people with MASL D or fatty liver disease are things like coronary artery disease and heart attacks and arrhythmias and heart failure, all related to the same risk factors that cause the liver disease often cause heart disease as well.

Sudipah Sarkar: What resources do you recommend to your patients for more education about MASLD?

Jamie Hamilton: We try and give a lot of education in our clinics, but we also refer patients to the Hopkins website for information about the Mediterranean diet, for example. That, that is really the main resource we use. And we give out in our after visit summaries, we give out information on diet plans and exercise plans.

Sudipah Sarkar: Dr. Hamilton, thanks so much for your time. It’s been great talking with you and thanks for sharing your recommendations and experience.

Jamie Hamilton: Great. [00:15:00] Thank you so much.