Volume 71, Issue 2, Pages 379-388 (August 2019) The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content  Yftach Gepner, Ilan Shelef, Oded Komy, Noa Cohen, Dan Schwarzfuchs, Nitzan Bril, Michal Rein, Dana Serfaty, Shira Kenigsbuch, Hila Zelicha, Anat Yaskolka Meir, Lilac Tene, Avital Bilitzky, Gal Tsaban, Yoash Chassidim, Benjamin Sarusy, Uta Ceglarek, Joachim Thiery, Michael Stumvoll, Matthias Blüher, Meir J. Stampfer, Assaf Rudich, Iris Shai  Journal of Hepatology  Volume 71, Issue 2, Pages 379-388 (August 2019) DOI: 10.1016/j.jhep.2019.04.013 Copyright © 2019 European Association for the Study of the Liver Terms and Conditions

Journal of Hepatology 2019 71, 379-388DOI: (10. 1016/j. jhep. 2019. 04 Copyright © 2019 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Hepatic fat content at baseline and after 18 months of intervention by subgroups. Bar values in the fig. are means ± SE of HFC, at baseline and after 18-month of intervention. Numbers represent relative changes. Data were analyzed using a repeated measures ANOVA across all subgroups. *p <0.05 for models without adjustment. $p <0.05 for models adjusted for visceral adipose tissue changes. Males and groups with higher BMI and visceral fat at baseline show larger decreases in HFC for both models. BMI, body mass index; HFC, hepatic fat content. Journal of Hepatology 2019 71, 379-388DOI: (10.1016/j.jhep.2019.04.013) Copyright © 2019 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Changes from baseline of the intake of energy and macro- and micro-nutrients between the diet intervention groups. Changes from baseline between the diet intervention groups in macro- and micro-nutrients. The Mediterranean/low-carbohydrate (MED/low-carb) diet more greatly decreased the intake of (A) carbohydrate, trans-fat and more greatly increased (B) nut consumption. (A) The low-fat diet more greatly decreased the intake of total fat, monounsaturated fat and cholesterol and tended to decrease polyunsaturated and saturated fat more. Analysis of variance with a covariance (ANCOVA) test was used. *p <0.05, #p <0.1. Carb, carbohydrate; Chol, cholesterol; Mono, monounsaturated fat; Poly, polyunsaturated fat; SFA, saturated fatty acids; Trans, trans-fat. Journal of Hepatology 2019 71, 379-388DOI: (10.1016/j.jhep.2019.04.013) Copyright © 2019 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Hepatic and cardiometabolic markers associated with 18 months hepatic fat content loss. Values are the β coefficients of the associations between 18-month changes in hepatic fat content and the indicated parameters at the X-axis. Multivariate model adjusted for age, sex and intervention groups (model 1); age, sex, intervention groups and body weight change (model 2); age, sex, intervention groups and visceral fat change (model 3). *p <0.05. %HbA1c, % glycated hemoglobin; ALT, alanine aminotransferase; Chol/HDL, total cholesterol to high-density lipoprotein ratio; GGT, gamma-glutamyl transferase; TG/HDL, triglyceride to high-density lipoprotein ratio. Journal of Hepatology 2019 71, 379-388DOI: (10.1016/j.jhep.2019.04.013) Copyright © 2019 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Effect of dietary strategies on cardiometabolic state beyond changes of weight, visceral and hepatic fat content. Values in the figure are means ± SE. The statistical analysis was performed by multivariate general linear regression models adjusted for age, sex, and baseline abdominal obesity. *p <0.05. The MOD model was further adjusted for 18-month weight changes (grey); 18-month visceral fat changes (green); 18-month hepatic fat changes (turquoise). Intention-to-treat analyses, including all 278 participants by multiple imputation technique. After 18 month of intervention, 38 participants dropped out and had incomplete sets of observations (86.3% adherence). Cardiovascular risk scores include the Framingham risk score, Systematic Coronary Risk Evaluation (SCORE), and the American College of Cardiology/American Heart Association (ACC/AHA). BP, blood pressure; CV, cardiovascular; MOD, mean-of-differences; TG/HDL, triglyceride to high-density lipoprotein ratio. Journal of Hepatology 2019 71, 379-388DOI: (10.1016/j.jhep.2019.04.013) Copyright © 2019 European Association for the Study of the Liver Terms and Conditions