Hirsh Trivedi, MD, on How I Treat MASH

Dr Hirsh Trivedi details how he approaches the diagnosis and management of metabolic-dysfunction associated fatty liver disease (MAFLD, formerly NAFLD) and metabolic associated steatohepatosis (MASH, formerly NASH.)

Hirsh Trivedi, MD, is an assistant professor of medicine and hepatologist at Cedars-Sinai Medical Center in Los Angeles, California.

Good morning. My name is Dr. Hirsh Trivedi and I'm currently an assistant professor of medicine at Cedar-Sinai Medical Center here in Los Angeles, California. I wanted to briefly talk to you about how I approach the treatment of MASLD and MASH, which was formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The first thing I do when I see a patient in my clinic with MASH is I try to identify their risk factor profile, particularly what are the risk factors for metabolic syndrome? Do they have insulin resistance or prediabetes or even type 2 diabetes, and if so, is it controlled or uncontrolled? Then I try to risk stratify their liver health by trying to determine whether they have the more severe form of MASLD called MASH, or do they have any liver fibrosis. Much of my initial workup is geared towards their fibrosis evaluation, since it is the worst predictor of liver related outcomes.

I typically try to start by getting noninvasive fibrosis measurement, usually with transient elastography, especially in those with a lower BMI below 35 and provided they have an ALT level below 100. However, if they do have an elevated BMI of 35 or above, or a high ALT above 100, then usually I go directly to MR-based elastography.

If there's any discordance in these results or any limitation in the findings of my noninvasive measurements or if I'm considering a coexisting diagnosis, then I will consider a liver biopsy to more definitively diagnose their fibrosis level and rule out other causes of their liver disease. If I find that the patient does have cirrhosis, then I'll go on to initiate cirrhosis-related screening protocols, particularly for liver cancer as well as portal hypertension related complications. If they have stage 3 level of scarring or fibrosis from mash, that also warrants liver cancer surveillance, and I typically do this with ultrasound plus alpha-fetoprotein level every 6 months.

If they have stage 2 to 3 level of fibrosis, I will then consider them for the newly FDA approved medication, resmetirom, which is at thyroid hormone receptor beta agonist, which may potentially help improve their level of fibrosis. If they don't have stage 2 to 3 fibrosis and if they have a limited stage of fibrosis classified as stage 0 or 1 fibrosis, then I really start focusing on improving their metabolic risk factor profile. If they have peripheral insulin resistance, I talk to them about ways of improving their insulin sensitivity.

Having said that, regardless of their fibrosis level, it's important to spend a lot of time trying to address these metabolic risk factors even in patients who have more advanced stages of fibrosis. For example, if I think a patient's elevated BMI or insulin resistance is the primary driver of their MASH liver disease, then I will counsel them on optimizing healthy lifestyle interventions. This includes increasing their weight resistance training, exercising regularly, at least 150 minutes per week as prescribed by national guidelines, also improving their protein intake and their nutrition.

Additionally, I try to emphasize the importance of maintaining some amount of skeletal muscle mass in these patients, especially because it's been linked to associated improved metabolic health. It improves metabolic insulin sensitivity if they have better skeletal muscle index, and it also improves other metabolic parameters that can contribute to the development or progression of MASH. Nutrition is also key, so I focus a few minutes every clinic visit on optimizing their nutritional status. I usually advocate for a plant-based diet with lean sources of protein. Typically, the Mediterranean diet has the most amount of evidence, but I also talk to my patients to ensure they're getting lean sources of protein, whether it be vegetable protein or meat such as chicken or fish.

Weight loss is obviously important and we usually aim for 5 to 10% of weight loss of their body weight. This has been shown to reverse the steatosis from MASH and also potentially some fibrosis if they have sustained weight loss. Of course, maintaining the sustained weight loss is really the challenge in these patients, so constant guidance, repeated counseling for lifestyle interventions, becomes very important. After I try lifestyle interventions for about 6 to 12 months, and depending on the severity of their metabolic risk factor profile, I do oftentimes resort to the new novel antiobesity medications, specifically the GLP-1 analogs or the GLP-1/GIP agonists in my practice, especially if it's for the right patient. Having said that, I try to counsel my patients on the importance of maintaining their lean muscle mass while on these medications since they can be associated with skeletal muscle loss, which can, I believe, in the long-term, worsen frailty down the line and lead to poor long-term outcomes. So it's vitally important that when you prescribe a patient these GLP-1 or combination therapies that we're continually counseling them on measures to improve their skeletal muscle health throughout, such as weight/ resistance training, cardiovascular activity, and increasing their protein intake is of paramount importance.

It's also important part of their management to try to engage other members of their health care team. For example, if a patient has a primary care physician or an endocrinologist or even is being seen in the weight loss clinic, it's important to make sure that each member of the team is involved in their care to provide a more cohesive/comprehensive approach to their care.

Ultimately, if none of these measures work, I oftentimes get the bariatric surgeons involved to see if the patient who has a severely elevated BMI may benefit from bariatric surgery. A lot of the evidence of bariatric surgery has shown that it can improve steatosis and even fibrosis in patients with MASH and MASLD, so whether this is a function of the weight loss associated with bariatric surgery or the surgery itself is yet to be determined, but this is one of the tools that we have in our toolbox that we could use to potentially optimize our patient's long-term outcomes.

Thank you so much for listening to this talk today, and I hope that you learn something on how to treat these patients with MASH.