2.5 NASH. What’s in a name? Mash and Nash both spell liver disease

Non-alcoholic steatohepatitis (NASH) and its precursor non-alcoholic fatty liver disease (NAFLD) have recently been redesignated as MASH and MASLD – metabolic dysfunction-associated steatohepatitis and metabolic dysfunction-associated steatotic liver disease, respectively. What hasn’t changed is the sheer difficulty of establishing clinical efficacy in these indications. They have long been known as a ‘silent killer’, owing to the asymptomatic nature of the pathology. And yet, the gradual accumulation of fat in the liver leads eventually to inflammation (or hepatitis), fibrosis (or scarring), cirrhosis (severe scarring), and, possibly to loss of function, liver failure, and liver cancer. Conducting clinical trials isn’t easy, given the slowly progressing course of the condition. Moreover, they also require numerous invasive tissue biopsies, to assess whether an investigational agent is having an effect. 

Madrigal Pharmaceuticals will learn on or before 14 March next whether the FDA will approve its application for resmetirom, which activates the thyroid hormone beta-receptor. If it’s successful, it could be the first of a slew of drugs that address a range of different targets. But will the rise of the skinny jabs (AKA the Glucagon-like receptor 1 agonists) provide an effective way of preventing fatty acid liver disease from progressing in the first place? 

Companies mentioned in this episode: 
AstraZeneca, Alnylam Pharmaceuticals, Boehringer Ingelheim, Intercept Pharmaceuticals, Ionis Pharmaceuticals, Madrigal Pharmaceuticals, Novo Nordisk, Madrigal Pharmaceuticals, Zealand Pharma

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