Enterohepatic Shunt-Driven Cholemia Predisposes to Liver Cancer

• DOI: 10.1053/j.gastro.2022.08.033
• Publication Date: 2022-08-18T15:17:17Z
• Authors: Beng San Yeoh; Piu Saha; Rachel M. Golonka; Jun Zou; Jessica L. Petrick; Ahmed A. Abokor; Xia Xiao; Venugopal R. Bovilla; Alexis C.A. Bretin; Jesús Rivera-Esteban; Dominick Parisi; Andrea A. Florio; Stephanie J. Wein...; Demetrius Albanes; Gordon J. Freeman; Amira F. Gohara; Andreea Ciudin; Juan M. Pericàs; Bina Joe; Robert F. Schwabe; Katherine A. McGlynn; Andrew T. Gewirtz; Matam Vijay-Kumar
• Keywords: Liver Cancer; Pathogenesis

Pathogenesis of hepatocellular carcinoma (HCC), which kills millions annually, is poorly understood. Identification risk factors and modifiable determinants mechanistic understanding how they impact HCC are urgently needed.We sought early prognostic indicators in C57BL/6 mice, we found were prone to developing this disease when fed a fermentable fiber-enriched diet. Such markers used phenotype interrogate stages development. Their human relevance was tested using serum collected prospectively from an HCC/case-control cohort.HCC proneness mice dictated by the presence congenitally present portosystemic shunt (PSS), resulted markedly elevated bile acids (BAs). Approximately 10% various sources exhibited PSS/cholemia, but lacked overt standard chow. However, PSS/cholemic compositionally defined diets, developed BA- cyclooxygenase-dependent liver injury, exacerbated uniformly progressed diets enriched with fiber inulin. progression cholestatic associated cholemia immunosuppressive milieu, both required that prevented impeding BA biosynthesis or neutralizing interleukin-10 programmed death protein 1. Analysis sera revealed future development HCC.PSS relatively common causes silent cholemia, predisposes injury HCC, particularly Incidence PSS/cholemia humans awaits investigation. Regardless, measuring may aid assessment, potentially alerting select individuals consider dietary interventions.