Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative...

Area of Science:

• Hepatology
• Genetics
• Personalized Medicine

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are leading causes of liver cirrhosis and hepatocellular carcinoma (HCC).
• Effective screening and management strategies for MASLD and MASH patients are urgently needed.

Purpose of the Study:

• To review genetic variations associated with MASLD and MASH pathogenesis.
• To evaluate the utility of polygenic risk scores (PRS) in predicting MASLD, MASH, cirrhosis, and HCC.
• To highlight the role of genetic susceptibility in personalized medicine for liver disease.

Main Methods:

• Narrative review of existing literature.
• Analysis of genetic variations (e.g., PNPLA3, TM6SF2, GCKR, MBOAT7, MERTK, HSD17B13).
• Evaluation of polygenic risk scores (PRS) as predictive markers.

Main Results:

• PNPLA3 genetic variants show a strong association with increased pathogenesis of MASLD, MASH, cirrhosis, and HCC.
• Polygenic risk scores (PRS) demonstrate superior predictive capability for MASLD, MASH, cirrhosis, and HCC compared to single-nucleotide polymorphisms.
• Therapeutic strategies targeting genetic variations (e.g., RNA interference for PNPLA3) are under development.

Conclusions:

• Genetic susceptibility, particularly PRS, are crucial predictive markers for MASLD and MASH.
• Personalized medicine approaches incorporating genetic insights are vital for future patient management.
• Multidisciplinary collaboration is essential for addressing complex challenges in MASLD and MASH.