Elsevier

Journal of Hepatology

Volume 62, Issue 4, April 2015, Pages 928-933
Journal of Hepatology

Research Article
Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: Association with the severity of liver disease

https://doi.org/10.1016/j.jhep.2014.11.030Get rights and content

Background & Aims

Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk, including coronary artery disease and cardiac dysfunction. In addition, recent evidence highlighted the possible role of epicardial fat as a new cardiometabolic risk factor. We tested the correlation between epicardial fat, alterations in cardiac geometry and function, and severity of liver damage, in patients with biopsy-proven NAFLD.

Methods

The anthropometric, biochemical and metabolic features were recorded in 147 consecutive biopsy-proven NAFLD cases (Kleiner score). Epicardial fat thickness was measured by echocardiography.

Results

Epicardial fat was higher in patients with severe vs. milder fibrosis (8.5 ± 3.0 vs. 7.2 ± 2.3 mm; p = 0.006); this association was maintained at multivariate logistic regression analysis (OR 1.22, 95%C.I. 1.01–1.47; p = 0.04) after correction for gender, age >50 years, visceral obesity, IFG/diabetes, non-alcoholic steatohepatitis and severe steatosis. Of note, 37.1% of patients with epicardial fat >7 mm (median value) had severe liver fibrosis, compared to 18.3% of the cases with lower epicardial fat (p = 0.01). As for echocardiographic indices, after adjusting for cardiometabolic confounders, diastolic posterior-wall thickness (p = 0.01), left ventricular mass (p = 0.03), relative wall thickness (p = 0.02), and left atrial volume (0.04), as well as ejection fraction (p = 0.004), lower lateral TDI e′ (p = 0.009), E/A ratio (0.04) (cardiac geometry alterations and diastolic dysfunction) were linked to severe liver fibrosis.

Conclusions

In patients with NAFLD, a higher epicardial fat thickness is associated with the severity of liver fibrosis, in keeping with a possible pathogenic role of ectopic fat depots in whole body organ damage. In addition, morphological and functional cardiac alterations are more pronounced according to the severity of fibrosis. Further studies are needed to validate our results.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, affecting roughly 20–30% of the general population [1]. In addition to an expected risk for disease progression from non-alcoholic steatohepatitis (NASH) to bridging fibrosis, cirrhosis and its complications [1], NAFLD patients are also at higher risk of early asymptomatic cardiovascular alterations and/or frank cardiovascular disease [2]. Specifically, NAFLD, diagnosed either by ultrasonography or by liver biopsy, has been associated with a higher prevalence of low coronary flow reserve [3], coronary calcification [4], and carotid atherosclerosis [5], [6], [7], well before the occurrence of cardiovascular events. These alterations have been partly associated with the severity of liver damage, measured by both lobular inflammation and fibrosis. Accordingly, cross sectional studies showed an association between NAFLD and the presence/extent of coronary, cerebral and peripheral cardiovascular involvement [8], whereas longitudinal studies identified NAFLD as a risk factor for incident cardiovascular events after adjustment for cardiometabolic confounders [9].

In the last few years, a number of studies also assessed the association between cardiac morphology or function, and the presence of NAFLD. Specifically, studies in small cohorts of subjects at high [10], [11] or low [12] cardiometabolic risk highlighted the association of an ultrasonographic diagnosis of NAFLD, after adjustment for metabolic confounders, with a significant impairment in echocardiographic diastolic function compared to non-NAFLD cases. Along this line, a recent study on a small cohort of NAFLD patients reported significant changes in cardiac structure and function as assessed by MRI, in the absence of metabolic changes or overt cardiac disease [13]. No data were, however, available on the impact of the severity of liver damage on these cardiac alterations. The complex interplay between liver fat and heart function has been further demonstrated by studies reporting an association between NAFLD and epicardial fat thickness. Epicardial fat thickness, assessed by either magnetic resonance imaging (MRI) [14] or echocardiography [15], [16], was higher in NAFLD subjects compared to non-NAFLD. In addition, a correlation was reported between epicardial fat thickness and ALT levels [17], the severity of ultrasonographic (US) [15] or MR spectroscopy [18] steatosis, and the Non-alcoholic Activity Score (NAS) in un-adjusted analyses [16].

In a consecutive cohort of patients with biopsy-proven NAFLD, we assessed whether epicardial fat is correlated to the severity of liver damage, and whether liver damage is linked to cardiac alterations in morphology and function.

Section snippets

Patients

The study involved 147 consecutive patients with NAFLD, recruited at the Gastrointestinal & Liver Unit of Palermo University Hospital, and fulfilling all the inclusion and exclusion criteria detailed below. Inclusion criteria were: (1) a histological diagnosis of NAFLD on a liver biopsy done less than 6 months before enrollment, showing steatosis (>5% of hepatocytes) with or without necroinflammation and/or fibrosis including cirrhosis. (2) The pre-biopsy assessment of NAFLD was based on

Patients

Mean age was 47 years, with a higher prevalence of males (64%) (Table 1). Eighty-five percent of patients fitted the criteria for visceral obesity, while IFG/diabetes, diabetes and hypertension were observed in 30%, 25%, and 35% of subjects, respectively. All subjects with diabetes or hypertension were drug-treated. Mean values for total, HDL-cholesterol, and triglycerides were within the normal range, and 6% of patients were on statins.

At liver biopsy, two thirds of patients had grade 2–3

Discussion

In a Western cohort of biopsy-proven NAFLD patients with a high prevalence of NASH and severe liver fibrosis, we observed that epicardial fat thickness is significantly associated with the severity of liver fibrosis, and that morphological and functional cardiac alterations by echocardiography are inversely correlated with the severity of liver damage. Of note, these associations were maintained after correction for both cardiometabolic and hepatic confounders.

Different lines of clinical

Financial support

This study was funded by grants from PRIN 2010–2011 (Prot. N. 2010C4JJWB).

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Authors’ contributions

S. Petta, M.C. Argano, D. Colomba, C. Cammà, V. Di Marco, D. Cabibi, A. Tutolomondo, G. Marchesini, A. Pinto, G. Licata, A. Craxì take full responsibility for the study design, data analysis and interpretation, and preparation of the manuscript. All authors were involved in planning the analysis and drafting the manuscript. All authors approved the final draft manuscript.

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