- Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, is characterized by fat storage in the liver, leading to inflammation and cellular damage. Patients suffering from it are at risk of progression to cyrrhosis, liver failure, or liver cancer.
- It is the most severe form of metabolic dysfunction-associated liver disease and shows a variable response to investigational drugs. Its symptoms are often silent or non-specific, which makes diagnosis difficult.
Madrid, July, 03, 2024.
MASH is a complex, multifactorial disease that requires a comprehensive approach integrating both liver and cardiovascular health. Formerly known as NASH (non-alcoholic steatohepatitis), it is characterized by difficulties in early detection and a variable response to investigational drugs. So far, no specific treatment for it has been approved, but several ongoing clinical trials currently focus on improving its management and prognosis.
It is the most severe form of metabolic dysfunction-associated liver disease (MASLD). It affects between 1.5% and 6.5% of the world population, showing an increase in its global prevalence in recent decades. It can be defined as the hepatic manifestation of a metabolic disorder and is characterized by fat storage in the liver, leading to inflammation and cellular damage. Patients suffering from it are at risk of progression to cyrrhosis, liver failure, or liver cancer. Moreover, these patients have an increased risk of developing cardiovascular disease.
Its symptoms are often silent or non-specific, which hinders and delays diagnosis. In its early stages, patients can present with fatigue or abdominal discomfort and may ignore their condition until they reach advanced stages of the disease. Liver biopsy is currently the standard method for diagnosing MASH; however, it is an invasive technique that entails some risks, which limits its application.
Health in Code’s MASH/NASH genetic testing
Health in Code works to understand how the genomics of MASH patients influences their therapeutic response to the drugs under development for the treatment of this disease, as well as to analyze the genetic cardiovascular risk inherent to each patient.
For this purpose, we have developed a MASH genetic panel to study both genetic variants related to the patient’s predisposition to develop or be protected against MASH (which will allow stratifying drug efficacty according to genetics) and genetic variants associated with the patient’s predisposition to cardiovascular risk. In the short term, this will help to understand drug safety, while in the long term it will allow guaranteeing the reliability of results from clinical trials.
The advantages of Health in Code’s MASH/NASH genetic panel
The MASH genetic panel developed by Health in Code allows analyzing the efficacy and safety of drugs under investigation in clinical trials from a genetic standpoint by a single test.
On one hand, in terms of prognostic assessment, the developed panel includes two validated polygenic risk scores (PRSs):
- PRS-NASH is based on the identification of five well-described polymorphisms associated with this disease in genes PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17813. This score is predictive of the development of liver cell carcinoma and NAFLD/NASH.
- PRS-CV includes 50 polymorphisms associated with the genetic risk of developing a cardiovascular event within the next 20 years. It defines five risk categories, of which the highest ones are the most informative. We have selected this model because of its accessible application in routine clinical practice and because its discrimination capacity does not substantially differ from those PRSs that include millions of variants.
On the other hand, the panel identifies polymorphisms in genes that show epidemiological evidence of their association with the development of one or several stages of the disease, from the development of fatty liver disease to steatohepatitis and fibrosis, either as risk factors or as protective factors. The report provided for each variant includes a brief clinical summary about the evidence for this association, along with literature references. It also discusses its potential association with the development of cardiovascular diseases, as well as the pathophysiological pathway in which the product of the gene containing the variant is involved.
The added value of Health in Code’s MASH/NASH genetic testing
Moreover, the design of the panel comprises the study of 419 genes related to rare monogenic diseases whose clinical manifestations include fatty liver. These diseases mainly correspond to some inborn errors of metabolism, disorders of lipid metabolism, and monogenic obesity, among others.
Additionally, Health in Code offers Olink proteomic analysis, which studies more than 3,000 proteins to complete the detection of omic biomarkers in MASH. This information is essential for understanding the disease at the molecular level and promoting the development of more accurate diagnostic tools, more effective therapies, and a more personalized approach to the management of this complex and increasingly prevalent liver disease.
Our aim is to help those companies that are striving to develop treatments for MASH, facilitating all the necessary technical and regulatory aspects for the development of genetic diagnosis, which must go hand in hand with any drug in order to guarantee treatment efficacy and safety for the benefit of the patients.
For more information, consult our clinical Atherosclerosis team: ateroesclerosis@healthincode.com.
