Liver Stiffness by Magnetic Resonance Elastography Is Associated With Increased Risk of Cardiovascular Disease in Patients With Non-alcoholic Fatty Liver Disease

Jung Gil Park; Jinho Jung; Kritin K. Verma; Min Kyu Kang; Egbert Madamba; Scarlett Lopez; Aed Qas Yonan; Amy Liu; Ricki Bettencourt; Claude Sirlin; Rohit Loomba

Disclosures

Aliment Pharmacol Ther. 2021;53(9):1030-1037. 

In This Article

Abstract and Introduction

Abstract

Background: Magnetic resonance elastography (MRE) is a reliable non-invasive alternative to liver biopsy for assessing liver fibrosis. There are limited data regarding an association between liver fibrosis by MRE and risk of cardiovascular disease (CVD).

Aim: To investigate the association of high-risk CVD phenotype determined by coronary artery calcification (CAC) with liver fibrosis by MRE in patients with non-alcoholic fatty liver disease (NAFLD).

Method: This was a cross-sectional analysis of well-characterised, prospective cohorts including 105 patients with NAFLD (MR imaging-derived proton density fat fraction ≥ 5%) with contemporaneous cardiac computed tomography (CT) and MRE. Patients were assessed using MRE for liver stiffness, and cardiac CT for the presence of CAC (defined as coronary artery calcium score > 0). Odds of presence of CAC were analysed using logistic regression analysis.

Results: The average age and body mass index were 54.9 years and 32.9 kg/m2 respectively. In this cohort, 49.5% of patients had CAC and 35.2% had significant liver fibrosis (defined as MRE ≥2.97 kPa). Compared to patients without CAC, those with CAC were older (50.0 [39.0–59.0] vs 63.0 [55.5–67.5], P < 0.001) and had higher Framingham risk score (FRS, 1.0 [0.5–3.5] vs 6.0 [2.0–12.0], P < 0.001). In multivariable-adjusted analysis, liver stiffness as a continuous trait on MRE was independently associated with the presence of CAC in a sex and age-adjusted model (adjusted odd ratios [aOR] = 2.23, 95% confidence interval [CI] = 1.31–4.34, P = 0.007) as well as in a FRS-adjusted model (aOR = 2.16, 95% CI = 1.29–4.09, P = 0.008). When analysed as a dichotomous trait, significant fibrosis (MRE-stiffness ≥2.97 kPa) remained independently associated with the presence of CAC in both FRS-adjusted model and sex and age-adjusted model (aOR = 3.21–3.53, P = 0.013–0.017). In addition, CAC was more prevalent in patients with significant fibrosis than those without as determined by MRE (67.6% vs 39.7%, P = 0.012).

Conclusion: Liver stiffness determined by MRE is an independent predictor for the presence of CAC in patients with NAFLD. Patients with NAFLD and significant fibrosis by MRE should be considered for further cardiovascular risk assessment, regardless of their FRS.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide, affecting approximately one fourth of the Western population.[1] NAFLD is a liver manifestation of metabolic syndrome characterised by hepatic fat accumulation ≥5%.[2,3] Although NAFLD can progress to fibrosis, cirrhosis and hepatocellular carcinoma, the most common cause of death in adults with NAFLD is cardiovascular disease (CVD).[4,5]

Many epidemiological studies have reported the association of NAFLD with increased risk of CVD.[6] While the evidence from these studies is robust, most non-invasive assessments of CVD risk, such as the Framingham risk score (FRS) and the atherosclerotic CVD risk algorithm, do not include the presence of NAFLD in calculating CVD risk.[7,8]

Due to NAFLD's high prevalence and heterogeneity of clinical course, it is important to identify predictors for incident CVD among patients with NAFLD.[4] Prior studies have reported that advanced fibrosis (stage ≥3) is associated with all-cause mortality in patients with NAFLD.[9,10] A recent study demonstrated the association of advanced fibrosis with incident CVD in a biopsy-proven NAFLD cohort.[11] However, liver biopsy is limited in clinical practice due to its invasiveness and sampling variability.[12] Non-invasive assessments for fibrosis based on indirect serum biomarkers such as NAFLD fibrosis score (NFS) and fibrosis-4 (FIB-4) index are also limited due to a significant proportion of patients being classified as having intermediate risk.[13]

Magnetic resonance elastography (MRE) is one of the most accurate non-invasive modalities for assessing liver stiffness[14] and has low technical failure rates compared with ultrasound-based elastography.[14] Recently, we demonstrated that liver stiffness by MRE is associated with increased CVD risk in patients with type 2 diabetes.[15] However, there are no data regarding association of liver stiffness by MRE with CVD risk in patients with NAFLD.

This study aimed to investigate the association of liver stiffness by MRE with high-risk CVD phenotype based on the presence of coronary artery calcification (CAC) in patients with NAFLD. Then, we further analysed the data with FRS of the patients to investigate association of significant fibrosis with risk of CVD.

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