Unveiling MASH: a comprehensive review highlighting experimental insights, molecular pathogenesis, and therapeutic approaches

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a widespread hepatic disorder that arises from metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterized by fat deposition throughout the hepatocytes accompanied by lobular inflammation that may eventually lead to progressive fibrosis. This is driven by different metabolic disturbances including hyperglycemia, hyperlipidemia, and obesity. Thus, the disease has a growing prevalence among the general population due to the widespread occurrence of these metabolic conditions. Patients with MASH have a much higher mortality rate compared to the general population or those without this inflammatory subtype of MASLD. MASH is accompanied by a high mortality rate, so it is considered a crucial point under study. OBJECTIVE: The current review outlines MASH features, its pathogenesis which is based on 'two hits' and 'multiple hits' theories and its great rate of incidence. The review also displays detailed explanations of the invasive and noninvasive methods for diagnosis focusing on NAS scoring system. Moreover, this review offers critical presentation of the most important experimental models and their drawbacks. Additionally, a summary of the substantial emerging pathways of molecular pathogenesis, therapeutic approaches (non-pharmacological and pharmacological), and up-to-date clinical drug trials are elucidated. CONCLUSION: Data presented in our review could facilitate understanding the molecular mechanisms involved in MASH development and interference by effective therapeutic modalities.