Treatment of Non-Alcoholic Steatohepatitis (NASH)

Introduction to NASH Treatment

The American College of Gastroenterology recommends lifestyle modification with a target weight loss of 7-10% as the cornerstone of NASH treatment, with pharmacotherapy reserved for biopsy-proven NASH with significant fibrosis (≥F2) 1, 2

For low-risk NASH (F0-F1 fibrosis), focus exclusively on lifestyle modifications without liver-directed pharmacotherapy 1
For high-risk NASH (F2-F3 fibrosis), intensive lifestyle modifications plus pharmacotherapy are recommended 1
High-risk NASH patients have approximately 10% risk of progression and require hepatologist-coordinated multidisciplinary care 3

Achieve 7-10% weight loss to significantly improve liver histology, reduce steatosis and inflammation, and potentially reverse NASH 1, 2
Implement a Mediterranean diet: reduced carbohydrates, increased monounsaturated and omega-3 fatty acids, rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil 1, 2
Prescribe 150-300 minutes of moderate-intensity exercise (3-6 metabolic equivalents) OR 75-150 minutes of vigorous-intensity exercise per week 3

For non-diabetic patients with biopsy-proven NASH and significant fibrosis (≥F2), vitamin E 800 IU daily is recommended 3, 1, 2
For diabetic patients with biopsy-proven NASH and significant fibrosis (≥F2), pioglitazone 30 mg daily is the first-line pharmacotherapy 1, 2
Consider GLP-1 receptor agonists, such as semaglutide, for diabetic NASH patients, particularly those with significant fibrosis (≥F2) 3, 1, 2

Use statins for dyslipidemia management—they are safe in NASH patients and have beneficial pleiotropic properties 3
Manage hypertension according to standard guidelines 3
Optimize glycemic control with glucose-lowering medications, prioritizing GLP-1RAs, SGLT2 inhibitors, and pioglitazone as they provide dual benefits for diabetes and NASH 3

Patients with FIB-4 >2.67, liver stiffness >12.0 kPa by transient elastography, or biopsy-proven clinically significant fibrosis should be managed by a hepatologist-coordinated multidisciplinary team 3