From the Guidelines
The optimal management of lean Metabolic Associated Steatohepatitis (MASLD) requires a multifaceted approach focusing on lifestyle modifications and targeted pharmacotherapy, prioritizing improvements in metabolic health and liver injury over weight loss. According to the most recent guidelines 1, the primary goal in managing lean MASLD is not weight reduction but rather enhancing metabolic health through dietary quality improvements. This involves reducing fructose and processed carbohydrates while increasing Mediterranean diet components, which have been shown to have added value for liver lipid reduction and cardiometabolic health 1.
Key lifestyle modifications include:
- Dietary improvements: Focusing on a Mediterranean diet pattern, limiting ultra-processed foods, and avoiding sugar-sweetened beverages 1.
- Regular moderate exercise: Prescribing 150-300 minutes of moderate exercise weekly, with an emphasis on both aerobic and resistance training, as this has been associated with reduced risk for liver fibrosis, cirrhosis, all-cause mortality, and hepatocellular carcinoma (HCC) 1.
Pharmacological interventions may also be considered:
- Pioglitazone (15-45 mg daily) has shown efficacy in improving insulin sensitivity in lean MASLD patients, despite potential mild weight gain 1.
- Vitamin E (800 IU daily) may be beneficial for non-diabetic patients with biopsy-proven NASH.
- GLP-1 receptor agonists like semaglutide can be considered in patients with comorbid diabetes.
Management should also address associated metabolic conditions, including diabetes, dyslipidemia, and hypertension. Regular monitoring with liver enzymes, non-invasive fibrosis tests, and imaging is essential, with follow-up every 3-6 months initially 1. This comprehensive approach targets the underlying pathophysiology of lean MASLD, which involves insulin resistance, dysfunctional adipose tissue, and genetic factors rather than excess adiposity alone.
From the Research
Optimal Management Approach for Lean MASLD
The optimal management approach for patients with lean Metabolic Associated Steatohepatitis (MASLD) involves a combination of lifestyle modifications and pharmacological interventions.
- Lifestyle modifications, such as a Mediterranean-like dietary pattern and individualized lifestyle interventions, are the cornerstone of MASLD treatment 2.
- A careful evaluation of alcohol intake and active treatment of all metabolic co-morbidities are also recommended 2.
- For "at-risk" MASH, reversal of fibrosis by one stage or resolution of MASH with no worsening in fibrosis as a surrogate end-point will need to be accompanied by overall survival benefits 2.
Pharmacological Interventions
Several pharmacological interventions have shown efficacy in treating MASLD, including:
- Thiazolidinediones (TZDs), vitamin E plus pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, and fibroblast growth factor-21 (FGF-21) analogue, which have a higher surface under the cumulative ranking curve (SUCRA) regarding NASH resolution 3.
- Obeticholic acid, lanifibranor, and silymarin, which have been shown to improve liver fibrosis stage 3.
Cardiovascular Morbidity and Mortality
Lean MASLD patients have a higher risk of cardiovascular mortality compared to non-lean MASLD patients, despite having a favorable cardiometabolic profile and comparable MACE rates 4.
- The odds of cardiovascular mortality are 50% higher in lean MASLD patients compared to non-lean MASLD patients 4.
- Lean MASLD patients also have a 40% higher odds of all-cause mortality compared to non-lean MASLD patients 4.
Clinical Implications
The management of lean MASLD patients requires a comprehensive approach that takes into account their unique clinical characteristics and risk factors.