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