How I Treat MASLD/MASH: Manal Abdelmalek, MD

Dr Abdelmalek reviews her approach to screening, diagnosis, treatment, and monitoring of metabolic dysfunction-associated steatotic liver disease.

Manal Abdelmalek, MD, is a professor of medicine and director of MASLD Clinical Research at Mayo Clinic in Rochester, Minnesota.

MASLD/MASH Management: Risk-Stratified, Patient-Centered Treatment Approach

• Metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH): Initial evaluation focuses on confirming hepatic steatosis (histology, imaging, or FibroScan with elevated CAP score) plus ≥1 cardiometabolic risk factor, followed by assessment of modifiable drivers, including diet, physical activity, alcohol use, hypertension, dyslipidemia, obesity, type 2 diabetes, and obstructive sleep apnea. Lifestyle modification remains first-line for simple steatosis without steatohepatitis or fibrosis.
• At-risk MASH with fibrosis: Fibrosis risk is assessed using FIB-4, FibroScan (VCTE), or MR elastography to guide therapy. FDA-approved liver-directed therapies include resmetirom (approved March 2024; improvement in steatohepatitis and fibrosis at 52 weeks) and semaglutide (Wegovy) (approved August 2025; comparable treatment effect with assessment at 72 weeks). Therapy selection is individualized based on fibrosis stage and cardiometabolic needs.
• Monitoring and long-term follow-up: Treatment response is reassessed with VCTE or MR elastography plus liver enzymes and cardiometabolic measures at 6 and 12 months. Patients with advanced fibrosis or cirrhosis undergo ongoing surveillance, including hepatocellular carcinoma screening every 6–12 months, MELD score monitoring, and liver transplant evaluation when MELD >15. Liver-directed therapies are currently recommended for fibrosis stages 2–3 and are not approved for cirrhosis.

Hello, my name is Manal Abdelmalek. I am the director of the MASLD Clinical Research Program and a professor of medicine here at the Mayo Clinic in Rochester, Minnesota. And I have been asked to address how do I treat MASLD and MASH for any patient that would come into my clinic.

I must say this is a very heterogeneous population of patients. I first evaluate a patient with the question of MASLD and MASH, which stands for metabolic dysfunction-associated steatotic liver disease and its progressive form of steatohepatitis. For their underlying risk factors, these patients need to have some evidence of a fatty liver, whether it be on prior histology or even any abdominal imaging study or FibroScan with an elevated CAP score in the presence of at least one cardiometabolic risk factor. And my first blush at a patient is really to evaluate their underlying drivers of disease.

I drill down into social alcohol use, diet, exercise, and their cardiometabolic risk factors, the presence or absence of high blood pressure, hypercholesterolemia or dyslipidemia, obesity or overweight status, type 2 diabetes and yes, even the presence of metabolic drivers such as untreated or undiagnosed obstructive sleep apnea. And my first dialogue with a patient is really to reverse any modifiable risk factor that we possibly can— converting from a Western diet to a more Mediterranean style diet with a reduction in social alcohol use, reduction in red meat intake, and certainly the avoidance of any sweetened beverages; increasing their physical activity and really tailoring it to what their likes or dislikes are. Exercise is only sustainable if you enjoy doing it and it doesn't really matter what approach they take, whether it be resistance or aerobic exercise as long as they do something. And so those are two modifiable approaches that I can take right away.

I may integrate nutritional counseling into that to help them drill down into the specific foods that they would enjoy eating and a change in diet that they can sustain hopefully for a lifetime. And then I really evaluate the patient's metabolic drivers, whether it be their weight, whether they have overweight or obese status, the presence or absence of impaired glycemic control or diabetes, cholesterol, and I treat each of these factors independently. So for patients who have high blood pressure, I will consider whether they're on an ACE inhibitor or an ARB, as there has been some evidence that these may improve clinical outcomes in MASLD and MASH. Certainly the treatment of dyslipidemia with a statin, as the leading cause of morbidity and mortality is cardiac. And so it really makes sense to treat the patient very holistically and there's no evidence that there is any risk for utilizing a statin in the context of underlying liver disease.

So I will liberally use statin therapy in my patients and then I really drill down and look at their glycemia presence or absence of diabetes and overweight status because that brings into the equation the potential use of GLP-1 agonists to improve both glycemia and overweight or obese status. And I modify any one of these risk factors. For patients who are lean and who don't have overweight or obese status, I may evaluate other risk factors a little bit more thoroughly such as celiac disease, ensure that I'm not missing Wilson's disease, and certainly am not overlooking obstructive sleep apnea as a modifiable risk factor. So I will drill down into symptoms of chronic fatigue, daytime somnolence or sleepiness, and maybe consider doing a sleep study.

After addressing that, I really need to assess where patients are in the spectrum of their disease. Patients who have simple steatosis without steatohepatitis or fibrosis will probably fare well with lifestyle modifications, whereas patients who have clinically significant steatohepatitis and clinically significant fibrosis will likely need liver-directed pharmacotherapy. So after evaluating the presence of MASLD and being confident that this is their underlying liver disease, I will do a second assessment of fibrosis risk. Now that may be in, a general practice, a FIT-4 score, but for my practice, I'll perform a point-of-care FibroScan or an assessment of elastography by MR elastography, because those patients who have evidence of chronic liver injury with increased liver stiffness, I start thinking about liver-directed pharmacotherapies. There are two approved right now by the FDA. We saw the approval of resmetirom in March of 2024 and subsequently semaglutide in the form of Wegovy in August of 2025.

But my approach to choice of therapies really becomes one that is patient-centered and individualized. I do have a detailed discussion with my patients about both therapies. The treatment effect size for both MASH resolution and fibrosis regression I believe is pretty comparable with both. Resmetirom demonstrated improvement in steatohepatitis and fibrosis at 52 weeks and semaglutide at 72 weeks.

And for those patients that have a reason to optimize their cardiometabolic risks, particularly those with diabetes or poorly controlled diabetes in the context of obesity, I will engage in a discussion first around a GLP-1 agonist, because my primary concern is a significant improvement in glycemia and potentially weight. And then after 6 months to a year of use of the GLP-1 agonist, considering whether they've had a treatment response or maybe need add-on therapy with resmetirom, I will perform a repeat FibroScan at 6 months along with liver enzymes and assessment of their cardiometabolic risks, their blood sugar, their lipids, an assessment of blood pressure, and work on continuing to modify these therapies and I will perform another assessment of treatment response at 12 months after initiation of a GLP-1. For patients who are risk averse to using an injectable therapy, then I will start off with resmetirom, but I'll also use resmetirom in patients with lean MASH who do not have significant need to lose weight urgently or markedly improve glycemic control as a primary driver of their disease.

Fortunately, these therapies may be used either in obesity or in lean MASH, but for patients who may be intolerant to the GLP-1 because of their gastrointestinal side effects or do not need to lose a substantial amount of weight or get glucose lowering, I may preferentially favor resmetirom as a first-line therapy, but I've had no reservations about using these therapies in combination or in synchrony. I do, however, not initiate them concomitantly because I at that juncture may not be able to discern which treatment is accounting for side effects if such side effects were to occur, but I do tailor my approach to initiation of treatment with a very detailed discussion with my patients about the risks, benefits, and alternatives to both and really allow the patient to guide next steps in therapy. Irrespective of what treatment I do initiate that's tailored to my patient, I will re-evaluate the same baseline surrogates of disease activity with a vibration control transient elastography or magnetic residency elastography both at 6 and potentially even 12 months to really assess whether there is reason for long-term therapy and whether an initial treatment response has occurred.

For patients with advanced hepatic fibrosis whose liver stiffness by VCTE is well above 15 or have had a historical biopsy demonstrating the presence of advanced hepatic fibrosis or cirrhosis, those patients really do remain in my practice for long-term assessment of liver synthetic function as well as routine surveillance and screening for hepatocellular carcinoma. I do alternate ultrasound-based assessments of liver cancers with an abdominal ultrasound alternating with magnetic resonance imaging or cross-sectional imaging every 6 months to a year, and I will routinely perform an assessment of MELD score in those patients with cirrhosis to ensure that they get timely referral for consideration of liver transplantation if they otherwise meet transplant eligibility with a MELD score of over 15.

So that's how I follow and assess my patients in my liver clinic — risk stratification, assessment of the presence or absence of at-risk MASH, an evaluation of the presence or absence of cirrhosis, and a tailoring of pharmacotherapies based on metabolic drivers of disease and liver-directed pharmacotherapy at this juncture, strictly for patients with fibrosis stage 2 and 3, recognizing that these therapies are not yet approved for use in patients with cirrhosis, although the GLP-1 therapies are approved for other indications such as obesity, sleep apnea or diabetes, and could be used in the context of patients with more advanced liver disease for those indications, semaglutide has been shown to be safe in cirrhosis but does not have any efficacy data in cirrhosis.

But for those patients, I do follow very carefully and routinely to ensure no complications of their treatment.