Yannan Xie, Xusheng Zhang, Bendong Chen
Research linking GLP-1RAs to the MASLD-MASH-HCC continuum is expanding rapidly. The available evidence suggests that GLP-1RAs are best investigated as upstream disease-modifying and risk-reducing agents in metabolically high-risk populations rather than as established direct anti-HCC therapies. Prospective studies with stage-specific liver and cancer outcomes are required to test this translational hypothesis.
BACKGROUND: Metabolic dysfunction increasingly shapes the burden of hepatocellular carcinoma (HCC) by linking obesity, type 2 diabetes, insulin resistance, and metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis, fibrosis, cirrhosis, and HCC. GLP-1 receptor agonists (GLP-1RAs) target several upstream metabolic drivers, but the structure and evolution of research connecting GLP-1RAs with the MASLD-MASH-HCC continuum remain unclear.
METHODS: We searched Web of Science Core Collection, PubMed, and Scopus for English-language articles and reviews published from January 1, 2000, to May 25, 2026. A GLP-1RA or related incretin concept was mandatory for inclusion, together with relevance to HCC and metabolic liver disease. After removal of 450 duplicates and relevance screening, 534 publications were analyzed for publication trends, collaboration networks, journals, authors, and keyword evolution. Bibliometric themes were subsequently interpreted through an expert synthesis of independent mechanistic and clinical evidence.
RESULTS: Research output accelerated after 2020; the United States remained the leading contributor, while China showed rapid recent growth. Keyword evolution shifted from glucose lowering, obesity, and insulin resistance toward MASLD/MASH, liver fibrosis, HCC risk, drug therapy, and clinical outcomes. These bibliometric patterns informed-but did not independently establish-a four-domain interpretive framework comprising systemic metabolic remodeling, intrahepatic lipotoxicity relief, inflammation-fibrosis regulation, and HCC risk and premalignant microenvironment modulation, with clinical translation considered across all four domains.
CONCLUSION: Research linking GLP-1RAs to the MASLD-MASH-HCC continuum is expanding rapidly. The available evidence suggests that GLP-1RAs are best investigated as upstream disease-modifying and risk-reducing agents in metabolically high-risk populations rather than as established direct anti-HCC therapies. Prospective studies with stage-specific liver and cancer outcomes are required to test this translational hypothesis.