Health. Towards a first treatment for “fatty liver” disease?

Health.  Towards a first treatment for “fatty liver” disease?

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“Metabolic dysfunction-associated steatohepatitis” (Mash, formerly called Nash) refers to the accumulation of fat in the liver disrupting lipid metabolism.

It mainly affects overweight individuals, those suffering from type 2 diabetes or those with metabolic syndrome.

It can progress to cirrhosis and hepatocellular cancer and even have consequences on brain health. The frequency of this disease, “initially anecdotal in the early 2000s, follows the trend of major metabolic diseases, with an increasing prevalence of severe forms”explains Dr Guillaume Lassailly, hepato-gastroenterologist (Lille University Hospital).

One figure among others to illustrate this progression: fatty liver disease (all stages of development combined) is expected to increase by 23% in the United States by 2050, according to a publication published at the American congress of the association on the study of liver diseases (AASLD), end of 2023.

30% disappearance of fatty liver thanks to resmetiron

After several years of unsuccessful research, several drug advances are emerging in Mash, including resmetiron (an oral THR-β agonist).

It is able to modulate fat (lipid) metabolism in the liver. “Thanks to this treatment, resolution of Mash would occur in 29.9% of patients treated with resmetirom dosed at 100 mg (compared to 9.7% in the placebo group)”specifies the specialist.

These figures come from the highly anticipated international study, Maestro-Nash, which has just been published in a major scientific journal. We finally have the first treatment for this inflammatory liver disease.

Who to treat?

In an editorial linked to the publication, Dr. Kenneth Cusi, an endocrinologist at the University of Florida, points out that with this drug, almost two in ten treated patients will experience resolution of their liver fat-related disease, while About one in ten will show improvement in fibrosis.

Fibrosis is the consequence of the accumulation of fat on the liver tissues which become fibrous.

But there remains a problem to resolve: who to treat? In fact, two thirds of patients do not respond to resmetirom. But due to the lack of specific markers (biological molecules or chemical substances), it is currently difficult to identify the people in whom this molecule could be effective, and the others.

To this end, international research programs on biomarkers are underway and some are subsidized by the European Commission.

Resmetiron is expected in the coming months in the United States and Europe. The United States Food and Drug Administration (FDA) granted provisional marketing authorization (MAA) to resmetirom on March 15.

To note : weight loss of at least 10% leads to a notable improvement in fatty liver disease (the amount of fat in the liver), reduces inflammation, and allows up to 80 to 90% disappearance of fatty liver disease ( Mash).

Source : Interview with Dr Guillaume Lassailly (Lille University Hospital); Harrison SA, Bedossa P, Guy CD, et al. MAESTRO-NASH Investigators. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024 Feb 8;390(6):497-509.

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