RT Journal Article
T1 Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.
A1 Fedirko, Veronika
A1 Tran, Hao Quang
A1 Gewirtz, Andrew T
A1 Stepien, Magdalena
A1 Trichopoulou, Antonia
A1 Aleksandrova, Krasimira
A1 Olsen, Anja
A1 Tjønneland, Anne
A1 Overvad, Kim
A1 Carbonnel, Franck
A1 Boutron-Ruault, Marie-Christine
A1 Severi, Gianluca
A1 Kühn, Tilman
A1 Kaaks, Rudolf
A1 Boeing, Heiner
A1 Bamia, Christina
A1 Lagiou, Pagona
A1 Grioni, Sara
A1 Panico, Salvatore
A1 Palli, Domenico
A1 Tumino, Rosario
A1 Naccarati, Alessio
A1 Peeters, Petra H
A1 Bueno-de-Mesquita, H B
A1 Weiderpass, Elisabete
A1 Castaño, José María Huerta
A1 Barricarte, Aurelio
A1 Sanchez-Perez, Maria-Jose
A1 Dorronsoro, Miren
A1 Quirós, J Ramón
A1 Agudo, Antonio
A1 Sjöberg, Klas
A1 Ohlsson, Bodil
A1 Hemmingsson, Oskar
A1 Werner, Mårten
A1 Bradbury, Kathryn E
A1 Khaw, Kay-Tee
A1 Wareham, Nick
A1 Tsilidis, Konstantinos K
A1 Aune, Dagfinn
A1 Scalbert, Augustin
A1 Romieu, Isabelle
A1 Riboli, Elio
A1 Jenab, Mazda
K1 Endotoxins
K1 Flagellin
K1 Hepatocellular carcinoma
K1 Lipopolysaccharide
K1 Prospective studies
AB Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
YR 2017
FD 2017-04-04
LK http://hdl.handle.net/10668/11045
UL http://hdl.handle.net/10668/11045
LA en
DS RISalud
RD Apr 19, 2025