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Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis

Madan, Shivank A.a; John, Febinb; Pyrsopoulos, Nikolaosc; Pitchumoni, Capecomorin S.b

European Journal of Gastroenterology & Hepatology: November 2015 - Volume 27 - Issue 11 - p 1237–1248
doi: 10.1097/MEG.0000000000000429
Review Article

Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19 274 adult participants: NAFLD=8652, controls=10 622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220–0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728–1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162–1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213–2.581, P=0.003), on pooling of 13 studies (14 445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840–1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457–1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.

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aDepartment of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York City, New York

bDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School/Saint Peters University Hospital, New Brunswick

cDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School/University Hospital, Newark, New Jersey, USA

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Correspondence to Shivank A. Madan, MD, MHA, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, 3400 Bainbridge Ave, MAP 7, New York, USA Tel: +1 281 216 5926; fax: +1 718 652 1833; e-mails:,

Received April 3, 2015

Accepted June 4, 2015

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