Fatty liver index, gamma-glutamyltransferase, and early... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Kozakova, Michaela1,*,†; Palombo, Carlo1; Eng, Marco Paterni2; Dekker, Jacqueline3; Flyvbjerg, Allan4; Mitrakou, Asimina5; Gastaldelli, Amalia2; Ferrannini, Ele1 ; and the RISC Investigators

1 From the Department of Internal Medicine, University of Pisa, Pisa, Italy

2 Fondazione Toscana G. Monasterio and Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche Pisa, Pisa, Italy

3 Department of Epidemiology and Biostatistics, EMGO VU University Medical Center, Amsterdam, The Netherlands

4 Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

5 Diabetes and Metabolism Unit, Department of Clinical Therapeutics, University of Athens, Athens, Greece

* Address reprint requests to: Department of Internal Medicine, University of Pisa, Via Roma, 67, 56122 Pisa, Italy.

E-mail:[email protected]

Received 9 September 2011; Accepted 28 November 2011

Potential conflict of interest: Nothing to report.

The European Group for the Study of Insulin Resistance (EGIR) RISC study was partly supported by EU grant QLG1-CT-2001-01252. Additional support has been provided by AstraZeneca (Södertälje, Sweden). The EGIR is supported by Merck (Santé, France).

† fax: +39 050 553235

View this article online atwileyonlinelibrary.com.

Abstract

An association between fatty liver and carotid atherosclerosis has been established; however, it is not clear whether this relationship is a consequence of shared conventional risk factors or whether it is determined by specific circulating factors originating from liver or adipose tissue. To identify the factors possibly linking fatty liver and atherosclerosis, we assessed, in 1,012 subjects free of confounding diseases (e.g., hypertension, diabetes, cardiovascular diseases, and dyslipidemia) and metabolic syndrome, the relationship between the presence of early plaques at carotid bifurcation and fatty liver index (FLI; a validated surrogate marker of fatty liver), as well as the associations between carotid plaque presence and established atherosclerotic risk factors, family history of cardiovascular disease (FH-CVD) or diabetes, insulin sensitivity, serum liver enzymes, adipokines, fatty free acids, and high-sensitivity C-reactive protein (hsCRP). A total of 55 of 1,012 subjects (5.4%) had small plaque at carotid bifurcation. Subjects with plaque were older and had higher prevalence of FLI ≥60 and FH-CVD, higher blood pressure, plasma low-density lipoprotein cholesterol, glucose, gamma-glutamyltransferase (GGT), and hsCRP, as compared to subjects without plaques ( P < 0.05). In a logistic regression model, adjusted for sex, liver transaminase, and alcohol consumption, the independent predictors of plaque presence were age ( P < 0.0005), FLI ≥60 ( P < 0.0005), and current smoking ( P < 0.05). When FLI in the model was replaced by variables used in its equation (e.g., body mass index, waist circumference, plasma triglycerides, and GGT), the independent determinants of plaque presence were age ( P < 0.001), GGT ( P = 0.001), and current smoking ( P < 0.05).

Conclusions:

Our cross-sectional study suggests that subjects with FLI ≥60 are at higher risk of atherosclerotic lesions, independently of established risk factors, and that serum GGT may represent a link between fatty liver and the development of early atherosclerosis. (Hepatology 2012)