Key Clinical Summary: Advanced Care Strategies for Metabolic Dysfunction-Associated Steatohepatitis

This is a micro-learning module summary of Dr Blanca Lizaola-Mayo's MASH Academy session which you can find here.

Before participating please read our CME and disclosure information which can be found here.

The MASH Academy was supported by an independent medical education grant from Novo Nordisk.

Introduction:

This summary addresses comprehensive care strategies for patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH), emphasizing a multidisciplinary approach, collaboration with various specialists, and patient education to enhance treatment adherence and outcomes.

Nomenclature Update:

• The term "non-alcoholic fatty liver disease" (NAFLD) has been replaced by Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
• "NASH" is now known as MASH (Metabolic Dysfunction-Associated Steatohepatitis).
• This change aims to be more affirmative, less stigmatizing, and to better reflect the cardiometabolic nature of the disease.
• MET-ALD refers to patients with MASLD and significant alcohol consumption.
• The presentation stresses the importance of recognizing the updated terminology.

Diagnosing MASLD:

• MASLD is diagnosed in patients with hepatic steatosis (on imaging) and at least one of five cardiometabolic risk factors:
• BMI ≥ 25 kg/m² (overweight) or increased waist circumference (ethnicity-specific cutoffs)
• Elevated glucose levels (fasting ≥ 100 mg/dL, 2-hour postprandial ≥ 140 mg/dL, HbA1c ≥ 5.7%) or type 2 diabetes
• Elevated blood pressure (≥ 130/85 mmHg) or antihypertensive medication use
• Elevated triglycerides (≥ 150 mg/dL) or anti-lipid medication use
• Low HDL cholesterol (< 40 mg/dL in men, < 50 mg/dL in women)
• It is important to accurately assess alcohol consumption in patients, as alcohol use disorder is prevalent and can overlap with MASLD (MET-ALD).

Epidemiology of MASLD:

• MASLD and MASH are increasingly prevalent.
• By 2030, MASLD is projected to become the leading cause of liver transplantation.
• Risk factors for MASLD include:
• Male sex
• Hispanic ethnicity
• Obesity
• Type 2 diabetes
• Hypercholesterolemia
• Hypertension
• The global prevalence of fatty liver disease is estimated to be 25-30%.
• There is an increased risk of MASH progression in post-menopausal women due to hypoestrogenism.

MASLD vs. MASH:

• MASLD: Hepatic steatosis (≥ 5% hepatocytes) without significant inflammation.
• MASH: Hepatic steatosis with inflammation and hepatocyte injury (ballooning).
• The distinction is important for patient education, as MASLD is often reversible.
• The presentation provides an overview of the natural history of MASLD, including the progression from steatosis to MASH, advanced fibrosis, and cirrhosis.
• MASH is reversible if cirrhosis has not developed.

Identifying Patients at Risk and Screening:

• Patients at high risk for MASLD should be screened. These include those with:
• Two or more cardiometabolic risk factors
• Type 2 diabetes
• Liver steatosis on imaging
• Elevated aminotransferases (ALT > 30 U/L in women, ALT > 40 U/L in men) for more than 6 months
• Referral to GI/hepatology is recommended for patients with:
• Indeterminate or high risk based on fibrosis risk stratification.
• Evidence of advanced liver disease.
• Abnormal liver enzymes for more than 6 months.

MASLD Treatment: Multidisciplinary Approach:

• A multidisciplinary, personalized approach is essential.
• Treatment components include:
• Lifestyle modifications (diet and exercise)
• Medications
• Weight loss interventions (bariatric surgery, endobariatrics)
• MASLD should be addressed as part of the metabolic syndrome, treating all associated conditions.
• A thorough review of the patient's medication list is crucial to identify and potentially switch obesogenic medications.

Lifestyle Modifications:

• Patient education is critical to emphasize the importance of diet and exercise.
• Weight loss of 3-5% can improve steatosis, 7% can improve MASH, and 10% or more can improve fibrosis.
• Patients should be advised that improvements in body composition (muscle gain, fat loss) may not always be reflected in scale weight.
• Dietary recommendations include:
• Calorie restriction (500-1000 calories/day)
• Limiting red meat, processed foods, and high-fructose foods
• Encouraging caffeinated coffee consumption (3 cups/day)
• Avoiding herbal supplements and dietary teas (except coffee)
• Vaccination against hepatitis A is recommended.
• Screening for other cardiometabolic diseases, such as sleep apnea (using the STOP-BANG questionnaire), is important.

Dietary Considerations in Cirrhosis:

• In patients with compensated cirrhosis and MASLD, weight loss of 5-10% is still recommended.
• Patients with obesity and cirrhosis should consume 15-20 kcal/kg/day and > 1.5 g/kg/day of protein.
• In decompensated cirrhosis, prolonged fasting should be avoided, and a high-protein diet with a nightly high protein snack is important.

Dietary Patterns and Exercise:

• The Mediterranean diet has shown the most cardiometabolic benefits.
• The best diet is the one the patient can adhere to.
• Alcohol should generally be avoided in patients with cirrhosis or advanced fibrosis.
• Exercise recommendations:
• 150-180 minutes of moderate-intensity exercise per week
• 75-150 minutes of vigorous-intensity exercise per week
• Exercise is not contraindicated in decompensated cirrhosis, but the type should be adjusted.
• Patients should be encouraged to find enjoyable forms of exercise for better adherence.
• Developing muscle mass is essential for improving insulin resistance and metabolic syndrome.

Weight Loss Interventions:

• Lifestyle modifications typically lead to about 5% weight loss.
• Combining lifestyle changes with other interventions can improve outcomes:
• Oral medications: ~10% weight loss
• Injectable medications (GLP-1s): 15-26% weight loss
• Bariatric surgery and endobariatrics: More significant weight loss

Pharmacological Treatments for Obesity:

• FDA-approved medications for obesity (GLP-1s, phentermine, orlistat, etc.) are being used in MASLD management.
• GLP-1 receptor agonists (e.g., semaglutide) are effective for weight loss.
• Studies show that weight loss is maintained with continued semaglutide use, but weight regain occurs after discontinuation.
• Common side effects of GLP-1s include gastrointestinal symptoms (nausea, vomiting, diarrhea).
• Tirzepatide (GLP-1 and GIP receptor agonist) is highlighted as a promising medication for weight loss and MASH treatment, showing significant weight loss and fibrosis reversal in clinical trials.
• The importance of educating patients about potential side effects and the need for ongoing treatment to maintain weight loss is emphasized.

Conclusion:

• MASLD is a prevalent condition requiring a comprehensive and multidisciplinary approach.
• Accurate diagnosis, lifestyle modifications, and management of cardiometabolic risk factors are crucial.
• Pharmacological interventions, especially GLP-1s, are playing an increasingly important role in MASLD treatment.
• Patient education and support are essential for treatment adherence and achieving optimal outcomes.