Background Extrahepatic cancers have been recognized as a significant outcome of non-alcoholic fatty liver disease (NAFLD)--redefined as metabolic dysfunction-associated steatosis liver disease (MASLD) with five cardiometabolic risk factors including hypertension which is associated with several cancers’ tumorigenesis or anti-cancer treatment. We aimed to investigate the association between hypertension, liver fibrosis and extrahepatic cancers in MASLD population.

Methods This multicenter cross-sectional study was based on MASLD population derived from hospital-based database across 11 centers in the nationwide of China, according to MASLD diagnostic criteria based on keywords and ICD-10 codes. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) between risk factors and extrahepatic cancers.

Results Totally 103,652 MASLD individuals were identified, with 6,605 diagnosed extrahepatic cancers. The primary outcome showed that hypertension (OR 1.15, 95% CI: 1.05, 1.26), and its combination with hyperglycemia (OR 1.33, 95% CI: 1.19, 1.48) were significantly associated with extrahepatic cancers in MASLD population. Over 40-year-old, female gender, AST/ALT over ULN were also risk factors. Metabolic-based treatments including ACEIs/ARBs (aOR 0.68, 95% CI:0.61,0.76), Fibrates (aOR 0.46, 95% CI:0.34,0.61), GLP-1 RA (aOR 0.54, 95% CI:0.37,0.79), and Thiazolidinediones (aOR 0.45, 95% CI:0.26,0.79) were significantly protective factors. After adjusting confounding factors, FIB-4 index associated with extrahepatic cancers in all age groups. In hypertension subgroup, FIB-4 between 1.3-2.66 and over 3.48 were associated with extrahepatic cancers in aged 35 to 65, consistent with those over 65 with FIB-4 over 2.

Conclusion Hypertension combined with liver fibrosis is associated with extrahepatic cancers in MASLD population.

The authors have declared no competing interest.

This study was funded by National Key R&D Program of China,named Exploration and Clinical Validation of Host-Gut Microbiota Co-metabolic Molecular Markers for MAFLD, Programme code 2022YFA1303800, named Host-Gut Microbiota Co-metabolic Mechanisms and Target Discovery in MAFLD, Project code 2022YFA1303804,and Chief Scientist Research Project of Hubei Shizhen Laboratory, code HSL2024SX0001.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was reviewed and approved by Beijing Tsinghua Changgung Hospital Ethics Committee, which waived the need for informed consent since the study only used deidentified databases, ID for ethics approval: 25469-0-01. We will adhere to all recommendations and requirements set forth by the board.

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All data produced in the present study are available upon reasonable request to the authors

Xinyue Zhao and Lai Wei are accepting full responsibility for the conduct of the study. They have access to the data and have control of the decision to publish.