Molecular mechanisms in MASLD/MASH-related HCC

Authors

Xiaobo Wang
Liang Zhang
Bingning Dong

Language

English

Publication Date

11-1-2025

Journal

Hepatology

DOI

10.1097/HEP.0000000000000786

PMID

38349726

PMCID

PMC11323288

PubMedCentral® Posted Date

8-13-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such as genetic mutations, carcinogen exposure, immune microenvironment, and microbiome. MASH-HCC exhibits distinct molecular and immune characteristics compared to other causes of HCC and affects both men and women equally. The management of early to intermediate-stage MASH-HCC typically involves surgery and locoregional therapies, while advanced HCC is treated with systemic therapies, including anti-angiogenic therapies and immune checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings while also providing the most current insights into the intricate molecular processes underlying MASH-HCC development. We delve into MASH-HCC-associated genetic variations and somatic mutations, disease progression and research models, multiomics analysis, immunological and microenvironmental impacts, and discuss targeted/combined therapies to overcome immune evasion and the biomarkers to recognize treatment responders. By furthering our comprehension of the molecular mechanisms underlying MASH-HCC, our goal is to catalyze the advancement of more potent treatment strategies, ultimately leading to enhanced patient outcomes.

Keywords

Humans, Carcinoma, Hepatocellular, Liver Neoplasms, Non-alcoholic Fatty Liver Disease, Tumor Microenvironment, Fatty Liver, MASH, MASLD, Fibrosis, Tumorigenesis, Tumor Microenvironment

Published Open-Access

yes

Recommended Citation

Xiaobo Wang, Liang Zhang, and Bingning Dong, "Molecular mechanisms in MASLD/MASH-related HCC" (2025). Faculty and Staff Publications. 4915.
https://digitalcommons.library.tmc.edu/baylor_docs/4915