How I Treat NASH (MASH)

Dr Lizaolo-Mayo discusses factors to consider when diagnosing and treating patients without obesity or overweight who may have metabolic-associated steatohepatitis (MASH).

Blanca Lizaolo-Mayo, MD, is the medical director of transplant hepatology at the Mayo Clinic in Scottsdale, Arizona.

TRANSCRIPT:

Good morning, everyone. Good day. I'm Blanca Lizaola Mayo. I am a transplant hepatologist at Mayo Clinic in Arizona. I am the medical director of the liver transplant center and it's for me a big honor to be here today talking to you about a quite prevalent disease called lean MASH.

As we know recently the nomenclature of what we used to know as nonalcoholic fatty liver disease or NAFLD as changed to a new name called MASLD or MASH. The reason why we wanted to change this nomenclature is because, number one, we wanted to remove the stigma around alcohol and fatty, and number two, we now understand that this is a little bit better and we wanted to have a name that really was able to explain in a better way what MASLD means.

So let's jump into that. What's MASLD? What we know about MASLD and the way that I see MASLD is the liver manifestation of metabolic syndrome. For example, when a person has high blood pressure, diabetes, obesity, prediabetes, and in some patients, like we're going to discuss today, even no obesity, however, they do have other metabolic risk factors, like high blood pressure as well or high cholesterol, sleep apnea or, for example, PCOS, these patients can develop MASLD.

Why? Because when the patients have fat accumulation in the liver and they have all these metabolic risk factors or metabolic syndrome, the liver manifestation of metabolic syndrome is MASLD. Now, we talked specifically about MASLD. We know that there are two categories. One is MASLD, where there's fat accumulation in the liver that is not causing inflammation. And the other one is where there's MASLD with inflammation. And this is the one that we call metabolic dysfunction-associated steatohepatitis (MASH). And this is important one, right? Because this is where we need to keep an eye on our patients as this can progress after several years into cirrhosis.

Just to give you a little bit of an example, we have patients that are considered rapid progressors, which means that around 20% of patients with MASH can progress to cirrhosis within 10 years. And on the other hand, normally in average, a normal patient can progress to cirrhosis in those with MASH every 7 to 10 years. However, why is so important to identify

MASLD or diagnosed MASLD and screen our patients for advanced fibrosis? When I mean advanced fibrosis, I mean stage 2 fibrosis or above. Liver fibrosis is divided into 5 different categories: stage 0 or F), where the patient does not have any degree of fibrosis or scar tissue in the liver; F1 where there's mild fibrosis; F2 where we start getting concerned that this is what we called advanced fibrosis. And the reason why we start getting concerned and the reason why we want to identify these patients that have stage 2 is because now we know that stage 2 or F2 is the one that is related to liver-related outcomes—for example, development of hepatocellular carcinoma, cardiovascular disease and progression to cirrhosis.  Stage three is when patients have more fibrosis in the liver and that fibrosis starts bridging. Up to here, this is reversible and it's one of the most important things that we need to tell our patients, that MASLD is a disease and MASH as well is a disease that can be treated and can be reverted. And stage 4, cirrhosis, end stage liver disease, which is not reversible.

The way that we diagnose MASLD nowadays is by finding hepatic acidosis of 5 or more percent through a cross-sectional imaging—for example, an ultrasound, a CT scan, or an MRI—plus 1 out of 5 cardiometabolic risk factors, which include having high blood pressure or being on medication’ having diabetes or prediabetes or being on medication for diabetes; having obesity or being overweight; having low HDL—less than 50 in women and less than 40 in men; and having high triglycerides.

So if we identify a patient that has hepatic steatosis or fat accumulation in the liver, plus one out of 5 cardiometabolic risk factors, and we have also ruled out other potential causes of steatotic liver disease—which means fat accumulation in the liver—this is how we diagnose MASLD.

Briefly, I want to mention what are the other potential causes of steatotic liver disease. We now know that alcohol use disorder or alcohol-related liver disease is another very important cause of liver disease in the world and there's a new nomenclature called Met-ALD because we have identified patients that have metabolic syndrome and also have heavy consumption of alcohol. We need to make sure that the patient is not consuming alcohol. We also need to make sure that the patient doesn't have other chronic liver diseases like, for example, hepatitis C, genotype 3 specifically, celiac disease, autoimmune hepatitis among others. And of course, there's always cryptogenic liver disease that can cause steatotic liver disease or medications, for example, prednisone, tamoxifen, or methotrexate.

So once we have ruled out, we have a diagnosis of MASLD. And how do we treat this? And how do we specifically treat this in patients with lean MASLD or lean MASH? Remember that there are a lot of patients that can have MASLD or MASH and have normal liver enzymes. So it's very important to be able to screen our patients for that advanced fibrosis of F2 that we already mentioned. The way that we classify lean MASLD is in those patients that are typical, they have a normal weight, meaning that BMI that we are still using from 19 to 24.9, which is considered normal weight. A patient is considered overweight when the patient has a BMI of 25 to 29.9 and is considered to have obesity once the patient goes beyond a BMI of 30.

It's very important to remember that in the Asian population, these cutoffs are different. And this is a population that tends to have more lean MASLD. We also see this in a lot of other Asian countries, for example. So in these patients, the cutoffs, as I mentioned, is a little bit different. The normal weight is considered from 18.5 to 22.9. Overweight is considered from 23 to 24.9 and obese is considered above 25. It's important to take this into account and remember that patients that are lean can also have MASLD and even MASH and this patients can progress to cirrhosis.

So how do we treat MASH and lean MASLD? The treatment of MASLD is exactly the same as the treatment for patients with that have obesity. How do we treat lean MASLD? It's very important to understand that MASLD and the culprit and the main thing to be able to treat MASLD is to treat the metabolic syndrome. If we see our MASLD patients as just looking at their liver, we're not going to be able to get anywhere. We need to treat all their comorbidities. We need to really improve that insulin resistance or that diabetes, make sure that our patients start exercising and start developing muscle mass, which is going to help them to decrease that metabolic syndrome.

As we already talked, the cut-offs for the Asian population are for lean muscle, they are a little bit different. However, in these patients, we still recommend for them to lose 3.5 % of their current weight. But being able to do this, they're going to be able to, number one, decrease the inflammation in the liver, number two, remove the fat in the liver, and number three, the liver is going to be able to regenerate and remove that fibrosis from the liver. When I see cpatients in clinic, I tend to ask them, number one, the reason why, for example, if they exercise or not, go through all their diet, really dig into that, because as we know, for example, in many Asian countries, their diet is heavily based on rice, for example. And as we know, it's a carbohydrate. So by making little changes throughout their diet, with the help of our nutritionists, we're able to make a big difference.

When we talk about prediabetes or insulin resistance, we have medications to treat this, for example. We know that metformin, for example, is a medication that is used throughout the world. But I have found this medication to be very helpful in those patients with lean MASLD with insulin resistance. That's one of the main effects, to decrease that insulin resistance, and if you pair this with exercise, the effect is going to be even better.

Other recommendations that I give to my patient is try to avoid alcohol completely. Normally, once we are able to revert that fibrosis or remove that steatosis or that accumulation of fat in the liver, that's when we start considering, you know, for them to have a glass of wine if they would like to have one. But remember, alcohol has a double hit. Number one, it has a lot of calories, and number two, it goes directly into the liver and hurts the liver.

Another thing that I always recommend for my patients is to avoid any type of supplements. As we know, the only thing that cleanses the liver is the liver itself. The only substance that has proven to be helpful for the liver is coffee, black caffeinated coffee, which I love. So the more coffee that you can drink, at least 3 cups of coffee per day, the better. And you will keep the hepatologist away, as I always say. And apart from that, we don't really recommend any other type of supplements.

If specifically for patients, if any of your relatives have some sort of liver disease or have been told to have fatty liver disease, I would recommend for them to ask their primary care providers to screen them for that advanced fibrosis that we mentioned. And the ways that we screen for advanced fibrosis is originally, or the first thing that we do is perform a FIB-4 score that is done by calculating and adding some laboratory workup with your age, with the patient's age. And depending on the FIB-4, we can determine if the patient does not have advanced fibrosis and these patients can continue with lifestyle modifications as we already discussed.

But if the patient actually is indeterminate or has high likelihood of having advanced fibrosis, this patient should be referred to a hepatologist for further treatment. As we know, and as you have heard in prior talks, the world around MASLD, obesity, diabetes is very exciting with introduction of these new medications, that GLP-1s. And recent data has shown that these medications are very effective for MASLD and that are also able to revert liver fibrosis. We also need to take into account that specifically the GLP1s, apart from having this excellent metabolic effect, unfortunately they will also make us lose muscle mass. So that's why teaching our patients and educating them regarding the importance of exercising and resistance training, it's so important.

So lastly, I would like to finish by saying that MASLD and lean MASLD or lean MASH is highly prevalent in the world. We know that number right now is the number 1 cause of chronic liver disease in the world, and it's expected to become the number 1 cause for liver transplantation by 2030. So it's important to screen our patients. It's important to be alert that our patients may have it despite having normal liver enzymes and we need to screens for that advanced fibrosis or F2 fibrosis. Thank you very much.