@article{3174719,
    title = "Exposure to bacterial products lipopolysaccharide and flagellin and
hepatocellular carcinoma: a nested case-control study",
    author = "Fedirko, Veronika and Hao Quang Tran and Gewirtz, Andrew T. and Stepien, and Magdalena and Trichopoulou, Antonia and Aleksandrova, Krasimira and and Olsen, Anja and Tjonneland, Anne and Overvad, Kim and Carbonnel, Franck and and Boutron-Ruault, Marie-Christine and Severi, Gianluca and Kuhn, and Tilman and Kaaks, Rudolf and Boeing, Heiner and Bamia, Christina and and Lagiou, Pagona and Grioni, Sara and Panico, Salvatore and Palli, and Domenico and Tumino, Rosario and Naccarati, Alessio and Peeters, Petra and H. and Bueno-de-Mesquita, H. B. and Weiderpass, Elisabete and Castano, and Jose Maria Huerta and Barricarte, Aurelio and Sanchez, Maria-Jose and and Dorronsoro, Miren and Quiros, J. Ramon and Agudo, Antonio and Sjoberg, and Klas and Ohlsson, Bodil and Hemmingsson, Oskar and Werner, Marten and and Bradbury, Kathryn E. and Khaw, Kay-Tee and Wareham, Nick and Tsilidis, and Konstantinos K. and Aune, Dagfinn and Scalbert, Augustin and Romieu, and Isabelle and Riboli, Elio and Jenab, Mazda",
    journal = "BMC Medicine",
    year = "2017",
    volume = "15",
    publisher = "BMC",
    issn = "1741-7015",
    doi = "10.1186/s12916-017-0830-8",
    keywords = "Hepatocellular carcinoma; Lipopolysaccharide; Flagellin; Endotoxins;
Prospective studies",
    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."
}