Fatty liver, an increasing global health concern
Metabolic dysfunction-associated steatotic liver disease (MASLD), commonly referred to as fatty liver disease, is becoming a global health concern, with over 30% of adults affected. In regions like South America and the Middle East, this rate can increase to 40%–45%. The buildup of excess fat in the liver not only contributes to an increase in cardiac and liver-related mortality but has also made MASLD a leading cause of liver transplants due to hepatocellular carcinoma (HCC) in many Western nations.
Given these increasing statistics, developing effective treatments to prevent the progression of MASLD/MASH to cirrhosis and its complications has been a major focus—and challenge—of liver disease research over the past decade. The goal has been to reduce liver-related morbidity and mortality in affected patients.
New treatment
Now, there’s promising news: the FDA has approved a new medication specifically targeting this condition—Resmetirom, previously known as MGL-3196, which will be marketed as ‘Rezdiffra.’
Resmetirom is an oral medication, liver-targeted thyroid hormone selective drug for the treatment of adults with non-cirrhotic MASH with moderate to advanced fibrosis. This new discovery could be seen as a breakthrough for the field and people affected by MASH.
Fatty liver and thyroid hormones association
Primary hypothyroidism is known to increase the risk of MASLD/MASH, and studies suggest they might be directly connected. Even in people with normal thyroid levels, severe liver disease can cause the liver to turn thyroid hormone T4 into an inactive form (rT3) rather than the active form (T3). Additionally, people with MASH often have issues with how thyroid hormones work in the liver, reducing their effectiveness.
There has long been a recognized connection between overt primary hypothyroidism and increased liver fat, with studies showing a clear correlation between higher serum thyrotropin (TSH) levels—a measure of the pituitary’s response to low thyroid hormone levels—and indicators of liver cell damage.
In a study with liver biopsies of patients with suspected MASH, even subjects with low-normal thyroid function (TSH level in the upper half of the ‘normal’ range), demonstrated increased probability of a MASLD diagnosis and a higher liver fibrosis stage.
These and other gathered data, encouraged researchers to try dosing ultra-low doses of thyroid hormone replacing therapy and remarkably without changes in circulating T3 and free T4 levels, levothyroxine treatment was able to reduce liver lipid content in patients with type 2 diabetes and MASLD. These findings indicate that thyroid hormones play a positive role in reducing fat buildup in the liver.
Resmetirom studies
In a recent study, 125 overweight or obese adults with MASH (confirmed by liver biopsy) were given Resmetirom 80 mg (about the weight of a business card) daily. This treatment was more effective than a placebo at reducing liver fat, especially with longer use.
Beyond reducing liver fat, Resmetirom also helped lower liver enzyme levels and markers of liver fibrosis. Patients who showed improvements in liver fat and liver tissue also reported better overall health and quality of life.
A larger study with 966 obese adults confirmed these findings, showing that Resmetirom works well over a longer period of time.
Results so far
Results of the whole investigational programme for this drug will help us understand if Resmetirom treatment will also aid in reduction of other liver related complications such as cirrhosis, liver transplant, hepatocellular carcinoma and, ultimately, mortality and not only in the cellular fatty infiltration.
Conclusion
As we acknowledge the FDA’s conditional approval of Resmetirom for treating adults with non-cirrhotic MASH and moderate to advanced fibrosis, it’s clear that significant challenges remain before it can be fully integrated into everyday clinical practice. Given the complexity of MASLD, which impacts multiple systems, the future of treatment may involve combining Resmetirom with other therapies. This could include medications that protect the liver and address the elevated risk of heart and metabolic problems associated with MASLD/MASH.
FOMAT Medical Research is leading the way in this crucial work, and we encourage you to participate in our ongoing MASH trials in California. Participants may be eligible for compensation for their time and travel. For more details on how you can get involved, please visit FOMAT Medical Research’s Active Trials page. Your participation could make a significant impact in the fight against MASLD and MASH.