C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients.
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but this remains controversial. We aimed to investigate whether associations between various features of NAFLD and hs-CRP are independent of body mass index (BMI) in its broad range among obese patients.


METHODS
A total of 627 obese adults (80% females), representing three cohorts from France and Belgium, had information on liver histology obtained from liver biopsies and measures of hs-CRP and BMI. We investigated whether the different features of NAFLD and BMI were associated with hs-CRP, with and without mutual adjustments using linear regression.


RESULTS
BMI and hs-CRP were strongly associated. Per every 10% increase in BMI the hs-CRP level increased by 19-20% (p<0.001), and adjustment for NAFLD-stage (including no-NAFLD) did not influence the association. We found no BMI-independent association between NASH and hs-CRP. However, a positive association between degree of steatosis and hs-CRP was observed (p<0.05) and this effect remained significant after adjusting for BMI, lobular inflammation, hepatocyte ballooning, and fibrosis. We found no significant associations between the other features of NAFLD and hs-CRP.


CONCLUSIONS
This study indicates that it is the accumulation of fat -both in the adipose tissue and in liver steatosis- that leads to increased hs-CRP levels among obese patients. Thus, hs-CRP may be a marker of steatosis, but not of severity of NAFLD, in obese patients.
Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark; Institute of Biomedical Sciences, University of Copenhagen, Denmark. Electronic address: ez@ipm.regionh.dk.
Esther
E
Zimmermann
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Rodolphe
R
Anty
INSERM, Nutriomique, U872, Paris F-75006, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris F-75006, France; Université Paris Descartes, UMR S 872, Paris F-75006, France; Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris F-75013, France; CRNH-Ile de France, Paris F-75013, France.
Joan
J
Tordjman
Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
An
A
Verrijken
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Philippe
P
Gual
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Albert
A
Tran
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Antonio
A
Iannelli
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Jean
J
Gugenheim
Assistance Publique-Hôpitaux de Paris, Beaujon Hospital, Pathology Department, Clichy F-92110, France; Centre de Recherche Bichat-Beaujon, INSERM U773, Clichy F-92110, France.
Pierre
P
Bedossa
Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
Sven
S
Francque
Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, "Hepatic Complications in Obesity", Nice, F-06204 Cedex 3, France; Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, F-06202 Cedex 3, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, F-06107 Cedex 2, France.
Yannick
Y
Le Marchand-Brustel
INSERM, Nutriomique, U872, Paris F-75006, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris F-75006, France; Université Paris Descartes, UMR S 872, Paris F-75006, France; Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris F-75013, France; CRNH-Ile de France, Paris F-75013, France.
Karine
K
Clement
Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
Luc
L
Van Gaal
Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
Thorkild I A
TIA
Sørensen
Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: TJS@ssi.dk.
Tine
T
Jess
D050154:Adiposity; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
D015415:Biomarkers; D002097:C-Reactive Protein