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

Fedirko, Veronika; Tran, Hao Quang; Gewirtz, Andrew T.; Stepien, Magdalena; Trichopoulou, Antonia; Aleksandrova, Krasimira; Olsen, Anja; Tjønneland, Anne; Overvad, Kim and Carbonnel, Franck, et al. (2017) In BMC Medicine 15(1).
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... (More)

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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keywords
Endotoxins, Flagellin, Hepatocellular carcinoma, Lipopolysaccharide, Prospective studies
in
BMC Medicine
volume
15
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85016932578
  • wos:000398034900001
ISSN
1741-7015
DOI
10.1186/s12916-017-0830-8
language
English
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yes
id
4639ae85-9e10-4c8b-a422-c74160a88d7b
date added to LUP
2017-05-08 14:00:51
date last changed
2017-09-18 11:35:25
@article{4639ae85-9e10-4c8b-a422-c74160a88d7b,
  abstract     = {<p>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 <sub>trend</sub> = 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.</p>},
  articleno    = {72},
  author       = {Fedirko, Veronika and Tran, Hao Quang and Gewirtz, Andrew T. and Stepien, Magdalena and Trichopoulou, Antonia and Aleksandrova, Krasimira and Olsen, Anja and Tjønneland, Anne and Overvad, Kim and Carbonnel, Franck and Boutron-Ruault, Marie Christine and Severi, Gianluca and Kühn, Tilman and Kaaks, Rudolf and Boeing, Heiner and Bamia, Christina and Lagiou, Pagona and Grioni, Sara and Panico, Salvatore and Palli, Domenico and Tumino, Rosario and Naccarati, Alessio and Peeters, Petra H. and Bueno-de-Mesquita, H B and Weiderpass, Elisabete and Castaño, José María Huerta and Barricarte, Aurelio and Sánchez, María-José and Dorronsoro,, Miren and Quirós, J Ramón and Agudo, Antonio and Sjöberg, Klas and Ohlsson, Bodil and Hemmingsson, Oskar and Werner, Mårten and Bradbury, Kathryn E and Khaw, Kay-Tee and Wareham, Nick and Tsilidis, Konstantinos K and Aune, Dagfinn and Scalbert, Augustin and Romieu, Isabelle and Riboli, Elio and Jenab, Mazda},
  issn         = {1741-7015},
  keyword      = {Endotoxins,Flagellin,Hepatocellular carcinoma,Lipopolysaccharide,Prospective studies},
  language     = {eng},
  month        = {04},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Medicine},
  title        = {Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma : A nested case-control study},
  url          = {http://dx.doi.org/10.1186/s12916-017-0830-8},
  volume       = {15},
  year         = {2017},
}