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Title: Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.
Authors: Fedirko, Veronika
Tran, Hao Quang
Gewirtz, Andrew T
Stepien, Magdalena
Trichopoulou, Antonia
Aleksandrova, Krasimira
Olsen, Anja
Tjønneland, Anne
Overvad, Kim
Carbonnel, Franck
Boutron-Ruault, Marie-Christine
Severi, Gianluca
Kühn, Tilman
Kaaks, Rudolf
Boeing, Heiner
Bamia, Christina
Lagiou, Pagona
Grioni, Sara
Panico, Salvatore
Palli, Domenico
Tumino, Rosario
Naccarati, Alessio
Peeters, Petra H
Bueno-de-Mesquita, H B
Weiderpass, Elisabete
Castaño, José María Huerta
Barricarte, Aurelio
Sánchez, María-José
Dorronsoro, Miren
Quirós, J Ramón
Agudo, Antonio
Sjöberg, Klas
Ohlsson, Bodil
Hemmingsson, Oskar
Werner, Mårten
Bradbury, Kathryn E
Khaw, Kay-Tee
Wareham, Nick
Tsilidis, Konstantinos K
Aune, Dagfinn
Scalbert, Augustin
Romieu, Isabelle
Riboli, Elio
Jenab, Mazda
Keywords: Endotoxins;Flagellin;Hepatocellular carcinoma;Lipopolysaccharide;Prospective studies
metadata.dc.subject.mesh: Adult
Carcinoma, Hepatocellular
Case-Control Studies
Cohort Studies
Immunoglobulin A
Immunoglobulin G
Liver Neoplasms
Middle Aged
Prospective Studies
Risk Factors
Issue Date: 4-Apr-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.1186/s12916-017-0830-8
Appears in Collections:Producción 2020

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