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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Authors: Veronika Fedirko, Hao Quang Tran, Andrew T. Gewirtz, Magdalena Stepien, Antonia Trichopoulou, Krasimira Aleksandrova, Anja Olsen, Anne Tjønneland, Kim Overvad, Franck Carbonnel, Marie-Christine Boutron-Ruault, Gianluca Severi, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Christina Bamia, Pagona Lagiou, Sara Grioni, Salvatore Panico, Domenico Palli, Rosario Tumino, Alessio Naccarati, Petra H. Peeters, H. B. Bueno-de-Mesquita, Elisabete Weiderpass, José María Huerta Castaño, Aurelio Barricarte, María-José Sánchez, Miren Dorronsoro, J. Ramón Quirós, Antonio Agudo, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Kathryn E. Bradbury, Kay-Tee Khaw, Nick Wareham, Konstantinos K. Tsilidis, Dagfinn Aune, Augustin Scalbert, Isabelle Romieu, Elio Riboli, Mazda Jenab

Published in: BMC Medicine | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
Authors
Veronika Fedirko
Hao Quang Tran
Andrew T. Gewirtz
Magdalena Stepien
Antonia Trichopoulou
Krasimira Aleksandrova
Anja Olsen
Anne Tjønneland
Kim Overvad
Franck Carbonnel
Marie-Christine Boutron-Ruault
Gianluca Severi
Tilman Kühn
Rudolf Kaaks
Heiner Boeing
Christina Bamia
Pagona Lagiou
Sara Grioni
Salvatore Panico
Domenico Palli
Rosario Tumino
Alessio Naccarati
Petra H. Peeters
H. B. Bueno-de-Mesquita
Elisabete Weiderpass
José María Huerta Castaño
Aurelio Barricarte
María-José Sánchez
Miren Dorronsoro
J. Ramón Quirós
Antonio Agudo
Klas Sjöberg
Bodil Ohlsson
Oskar Hemmingsson
Mårten Werner
Kathryn E. Bradbury
Kay-Tee Khaw
Nick Wareham
Konstantinos K. Tsilidis
Dagfinn Aune
Augustin Scalbert
Isabelle Romieu
Elio Riboli
Mazda Jenab
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0830-8

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