Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism

Area of Science:

• Hepatology
• Epigenetics
• Metabolomics

Background:

• Abnormal epigenetic patterns are key drivers in metabolic-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC) progression.
• Research highlights the interplay between epigenetics and metabolic pathways in MASLD-associated HCC, suggesting reversible epigenetic changes as therapeutic targets.
• Diverse etiologies of HCC present challenges in identifying effective epigenetic targets.

Purpose of the Study:

• To summarize key factors in MASLD-driven hepatocarcinogenesis.
• To explore epigenetic mechanisms in MASLD-associated HCC.
• To present the bidirectional interplay between metabolomics and epigenetics in MASLD-associated HCC and discuss therapeutic strategies.

Main Methods:

• Literature review focusing on epigenetic modifications and metabolic reprogramming in MASLD-associated HCC.
• Analysis of the bidirectional relationship between metabolomic changes and druggable epigenetic alterations.
• Synthesis of current understanding of hepatocarcinogenesis driven by MASLD.

Main Results:

• Epigenetic alterations are crucial in MASLD progression and HCC development.
• Targeting metabolic reprogramming, particularly lipid anabolism, shows promise for MASLD-associated HCC.
• A comprehensive understanding of metabolomic changes linked to epigenetic modifications is vital.

Conclusions:

• Epigenetic modifications and metabolic reprogramming are intricately linked in MASLD-associated HCC.
• Reversible epigenetic changes offer potential therapeutic avenues.
• Targeting both epigenetic and metabolomic alterations presents a promising strategy for treating MASLD-associated HCC.