Treatment of Non-Cirrhotic MASH with Significant Liver Fibrosis (Stage ≥2)
This protocol addresses adults with metabolic dysfunction-associated steatotic liver disease (MASLD) presenting specifically as non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with confirmed significant liver fibrosis at stage 2 or above, with cirrhosis excluded.
Clinical Scenario
Non-cirrhotic MASH with significant liver fibrosis (stage ≥2) represents a distinct and clinically important sub-population within MASLD. Confirmed absence of cirrhosis is a defining prerequisite for this treatment pathway. Histological assessment establishes the fibrosis stage prior to initiating MASH-targeted therapy.
Approach to Treatment
An oral, liver-directed thyroid hormone receptor beta agonist is the MASH-targeted therapy recommended for eligible adults in this population, based on histological efficacy demonstrated in a large phase III registrational trial. The full protocol — including complete eligibility criteria and all structured treatment parameters — is available via the regimen below.
Treatment Goals
- Resolution of steatohepatitis without worsening of fibrosis
- Regression of at least 1 fibrosis stage without worsening of steatohepatitis
- Greater than 30% reduction in hepatic lipid content by MRI-PDFF
- 120% increase in sex hormone-binding globulin
References
DOI: 10.1016/j.jhep.2024.04.031
If approved locally and dependent on the label, adults with non-cirrhotic MASH with significant liver fibrosis (stage >2) should be considered for treatment with resmetirom as a MASH-targeted therapy, as this treatment demonstrated histological efficacy on steatohepatitis and fibrosis in a large phase III registrational trial with an acceptable safety and tolerability profile (LoE 2, strong recommendation, consensus).
As per regulatory guidance, the primary endpoints in registrational phase III clinical trials for non-cirrhotic MASH are: (a) resolution of steatohepatitis without worsening of fibrosis and (b) regression of at least 1 stage in fibrosis without worsening of steatohepatitis.
In the MAESTRO-NASH trial, a >30% reduction in hepatic lipid content by MRI-PDFF and a 120% increase in SHGB were associated with a positive treatment response.
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