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Metabolic-associated steatotic hepatitis (MASH) is primarily managed through lifestyle modifications, such as adopting a restricted diet high in antiinflammatory ingredients like fruits, vegetables and whole grains, planned exercise routines and cutting out alcohol. However, precision medicine approaches are also showing promise for not only managing the condition, but improving the diagnostic process, enabling early detection and preventing disease progression. Below, we explore the data-driven insights precision medicine is starting to enable in MASH.
Emerging biomarkers
Several biomarker types have now been identified for MASH, including lipid-related biomarkers and insulin resistance markers, as well as promising indications of genetic associations. For example, one study reported improved prediction of MASH based on genetic risk variants in the PNPLA3, TM6SF2, and FNDC5 genes. Additionally, another study was able to show that a combination of genetic variants in the PNPLA3, TM6SF2 and MBOAT7 genes was able to improve the accuracy of predicted hepatocellular carcinoma (the most common type of liver cancer), in MASLD patients.
Advances in diagnostic tools
Advances in data analysis and diagnostic tools are also aiding the development of precision medicine approaches for MASH, which is an often silent condition that is under-diagnosed. The recently developed NIS4 and SomaSignal tests, which use blood samples to analyze various biomarkers to identify patient risk, have been able to successfully identify patients at risk of developing MASH.
The development of the FAST algorithm, a non-invasive statistical analysis tool, has also been able to successfully identify MASH patients. This predictive logistic regression-based algorithm uses Fibroscan data to identify and diagnose MASH without the need for patients to undergo an invasive liver biopsy.
Targeted therapies
In March 2024, the US Food and Drug Administration approved resmetirom as the first ever drug specifically for the treatment of MASH. The drug, which is an agonist of thyroid hormone receptor-β which promotes fat metabolism in the liver and helps prevent damage, is able to support resolution of MASH and aid improvement of fibrosis. Importantly, the FDA’s approval of resmetirom does not require patients to undergo liver biopsy in order to qualify for the treatment, reducing patient burden and making the therapy more accessible.
At the same time there are several other exciting therapies targeting specific genetic and metabolic pathways which are currently in late stage clinical trials. Novo Nordisk’s Phase III ESSENCE trial is due to finish at the end of 2024 and is focused on demonstrating the efficacy of semaglutide, a GLP-1 receptor agonist already approved for use in obesity and Type 2 Diabetes, for treatment of MASH.
In October 2024, pharmaceutical giant Boehringer Ingelheim was also granted breakthrough therapy designation for survodutide, which is intended to treat MASH patients with moderate or advanced fibrosis. In light of this new designation the company has launched two Phase III clinical trials, LIVERAGE and LIVERAGE-Cirrhosis, focusing on patients with moderate or advanced fibrosis and on those with liver cirrhosis.
For more information, please download our complimentary full report on the state of precision medicine in cardiovascular and metabolic disease.
