Hypertension associated with the risk of extrahepatic cancers in MASLD population: a multicenter cross-sectional study in China

  1. Xinyue Zhao
  2. Feng Xue
  3. Shanshan Wang
  4. Haiyun Ding
  5. Dong Li
  6. Huiying Rao
  7. Fanpu Ji
  8. Jidong Jia
  9. Xiong Ma
  10. Peng Hu
  11. Xiaoguang Dou
  12. Keshu Xu
  13. Shuangqing Gao
  14. Ming Yang
  15. Lai Wei
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Abstract

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.

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  1. Version published to 10.1101/2025.07.28.25332237 on medRxiv