Complexity of metabolic dysfunction-associated steatotic liver disease: State of the art review

This article reviews the advancements made in the diagnosis and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH). For inhibition of the MASLD progression, newly approved thyroid hormone receptor β agonists and potential agents, including farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists, and or GIP/GLP-1/glucagon receptor co-agonists, offering new prospects for the pharmacological management of MASLD. Lifestyle interventions, particularly personalized dietary and exercise regimens, as well as multidisciplinary collaboration, are recognized as vital components of treatment strategies. Although surgical options can yield significant benefits in certain cases, their risks and the criteria for patient selection necessitate more stringent research and guidance. Given the complexity of MASLD-related hepatocellular carcinoma (HCC), various insulin resistance, oxidative stress, gut-liver axis dysregulation, genetics, and epigenetics-based anti-tumor treatments have been ongoing explored to improve outcomes. Considering the global prevalence of MASLD and the relatively young age of disease onset, healthcare providers should be more vigilant in the timely diagnosing of MASLD progression to MASH, cirrhosis, and HCC. Likewise, regular medical check-ups are essential for early disease diagnosis and prevention before the development of complications, thereby improving their overall quality of life. Significant progress has been made in the research surrounding MASLD, MASH, and HCC, instilling new hope for future clinical practices.