Original article
Pancreas, biliary tract, and liver
Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Nonalcoholic Steatohepatitis

https://doi.org/10.1016/j.cgh.2015.01.027Get rights and content

Background & Aims

The association between quantity of liver fat and the presence of metabolic syndrome needs to be assessed systematically. We aimed to determine the association between the quantity of liver fat and the presence of the metabolic syndrome in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), independent of nonalcoholic steatohepatitis (NASH).

Methods

We recruited 146 patients with well-characterized biopsy-proven NAFLD and 50 individuals without NAFLD (controls) to participate in a case–control study at the NAFLD Translational Research Unit at the University of California San Diego. Liver fat was quantified in patients with NAFLD and controls using an advanced magnetic resonance imaging–based biomarker, the proton-density-fat-fraction (MRI-PDFF). Patients with NAFLD were divided into groups based on whether they were above or below the median MRI-PDFF value (15.4% in patients with NAFLD); the MRI-PDFF value for controls was less than 5%. The primary outcome was the presence of the metabolic syndrome using Adult Treatment Panel III criteria without and with adjustment for the presence of NASH.

Results

Compared with NAFLD patients with MRI-PDFF values below the median, and compared with controls, NAFLD patients with MRI-PDFF values above the median were more likely to have abdominal obesity (P < .0001), lower levels of high-density cholesterol (P < .0001), higher levels of triglycerides (P < .0001), and higher fasting glucose levels (P < .001). Compared with NAFLD patients with MRI-PDFF values below the median, NAFLD patients with MRI-PDFF above the median were more likely to have the metabolic syndrome (60.3% vs 44.4%; P < .04), independent of biopsy-detected NASH.

Conclusions

Increased liver fat content in patients with NAFLD is associated with increased rates of the metabolic syndrome, independent of NASH. There appears to be an association between the quantity of liver fat and the risk for cardiovascular disease in patients with NAFLD.

Section snippets

Study Design and Patient Population

This was a cross-sectional analysis of a case–control study of 146 patients with biopsy-proven NAFLD and 50 uniquely well-phenotyped controls without NAFLD. Liver fat quantification was performed in both patients with NAFLD and non-NAFLD controls by an advanced MRI-based noninvasive biomarker: the MRI-PDFF. NAFLD patients were divided into 2 groups, a priori, 73 patients above and 73 patients below the median MRI-PDFF (the median MRI-PDFF value was 15.4% in patients with NAFLD), and 50

Demographic Characteristics

The baseline characteristics of patients with biopsy-proven NAFLD, stratified into 2 groups, 1 group above and 1 group below the median MRI-PDFF (15.4%), and controls without NAFLD, are shown in Table 1. The 3 groups were similar in age and sex distribution. As expected, both NAFLD groups had a significantly higher body weight (P < .0001) and body mass index (P < .0001) than non-NAFLD controls (Table 1).

Quantitative Evaluation of Metabolic Syndrome Traits

Compared with NAFLD patients with MRI-PDFF values below the median liver fat content of

Discussion

By using a uniquely well-phenotyped cohort of patients with and without NAFLD, we showed that an increased quantity of liver fat is associated with an increased prevalence of the metabolic syndrome independent of NASH. Among our cohort of 146 patients with biopsy-proven NAFLD, the metabolic syndrome was present in 60.3% of patients with PDFF above the median vs 44.4% in patients with PDFF below the median (P < .04). This difference remained statistically significant even after adjusting for the

Conclusions

Increased liver fat content in NAFLD is associated with increased rates of the metabolic syndrome independent of NASH. In contrast with conventional thinking that liver fat quantity is inconsequential among patients with biopsy-proven NAFLD, these data suggest the prognostic association between liver fat quantity and increased metabolic risk in NAFLD. Further studies are needed to show whether a reduction in liver fat quantity can decrease metabolic risk in NAFLD.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported in part by the American Gastroenterological Association Foundation (Sucampo) Association of Specialty Professors Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award (R.L.); and by Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, the American Gastroenterological Association (K23-DK090303-02), and the Clinical and Translational Research Institute at the University of California, San Diego, which is funded from awards issued by the National Center for Advanced Translational Sciences (UL1RR031980). The study sponsor(s) had no role in the study design, collection, analysis, or interpretation of the data, or drafting of the manuscript.

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