Περίληψη:
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.
Συγγραφείς:
Fedirko, Veronika
Hao Quang Tran
Gewirtz, Andrew T.
Stepien,
Magdalena
Trichopoulou, Antonia
Aleksandrova, Krasimira and
Olsen, Anja
Tjonneland, Anne
Overvad, Kim
Carbonnel, Franck
and Boutron-Ruault, Marie-Christine
Severi, Gianluca
Kuhn,
Tilman
Kaaks, Rudolf
Boeing, Heiner
Bamia, Christina and
Lagiou, Pagona
Grioni, Sara
Panico, Salvatore
Palli,
Domenico
Tumino, Rosario
Naccarati, Alessio
Peeters, Petra
H.
Bueno-de-Mesquita, H. B.
Weiderpass, Elisabete
Castano,
Jose Maria Huerta
Barricarte, Aurelio
Sanchez, Maria-Jose and
Dorronsoro, Miren
Quiros, J. Ramon
Agudo, Antonio
Sjoberg,
Klas
Ohlsson, Bodil
Hemmingsson, Oskar
Werner, Marten and
Bradbury, Kathryn E.
Khaw, Kay-Tee
Wareham, Nick
Tsilidis,
Konstantinos K.
Aune, Dagfinn
Scalbert, Augustin
Romieu,
Isabelle
Riboli, Elio
Jenab, Mazda
