BACKGROUND/AIMS:The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) is multifactorial, with evidence suggesting a protective role for the soluble receptor for advanced glycation end-products (sRAGE). While gut microbiota dysbiosis and MASLD have been linked, evidence of their association with sRAGE remains limited. We aimed to test the prospective association between serum sRAGE levels and MASLD and to explore associated patterns of gut microbiota composition. METHODS:A prospective cohort study assessed serum sRAGE levels and MASLD at two time points, with new-onset or persistence of MASLD evaluated by ultrasonography or controlled attenuation parameter. A cross-sectional analysis was performed on a sub-sample with gut microbiota measurements using 16S rRNA sequencing (V3-V4, Illumina MiSeq). RESULTS:Among 289 subjects in the prospective analysis (mean follow-up: 6.67 ± 0.73 years, mean age: 58.54 ± 6.54 years, 57.8% men), low sRAGE levels were associated with 2.22-fold greater odds of new-onset/persistent MASLD (95% CI 1.15-4.26, p = 0.017), with a dose-response association across sRAGE tertiles. The cross-sectional analysis with a subsample of 136 subjects showed significant α- and β-diversity differences between MASLD and non-MASLD groups. Moreover, β-diversity variation across sRAGE groups resembled that observed between the MASLD groups. Shared taxa linked to low sRAGE levels and MASLD included Streptococcaceae, Enterobacteriaceae, Streptococcus, Dorea, and Klebsiella. Non-MASLD and high sRAGE levels were associated with Christensenellaceae, Akkermansiaceae, Christensenellaceae R-7 group and Akkermansia. CONCLUSIONS:Low sRAGE levels are associated with higher odds of MASLD. MASLD and low sRAGE levels share a similar gut microbiota signature, suggesting a potential biological link that warrants further investigation.

Background & Aims High intake of ultra-processed food (UPF) and its subcategories of processed meats, snacks, and beverages is associated with increased cardiometabolic risk. This study aimed to assess the validity of a Short Processed Food Questionnaire (SPFQ) against a validated food frequency questionnaire (FFQ) and to explore the predictive validity for metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic outcomes. Methods A validation and a prospective cohort study, including adults who participated in a metabolic and hepatic screening survey at Tel-Aviv Medical Center and arrived to follow-up at least five years later. MASLD was evaluated by ultrasound/controlled attenuation parameter. At baseline, participants completed a 118-item FFQ; 49 items were classified as UPF (NOVA 4). The 23-item SPFQ includes 15 UPF items, which were mapped to FFQ data to simulate responses. Relative validity was assessed by comparing UPF estimates using paired t-tests, Pearson correlation, and tertile agreement with weighted kappa. Predictive validity was evaluated by multivariable logistic regression. Results A total of 789 subjects were included. Correlations between the two questionnaires were strong for total UPF and its subcategories processed meat, snacks, and beverages (r≥0.91; all P<0.001). Tertile agreement across total UPF and subcategories was high, with 78.3%, 90.0%, 94.6%, and 96.5% classified in the same tertile by both questionnaires (kappa≥0.81; all P<0.001). In the prospective cohort (n=316; mean follow-up 6.7 years), the highest UPF tertile by SPFQ was associated with higher odds of new-onset/persistent metabolic syndrome (OR=2.05, 95%CI 1.10–3.83), hypertension (2.37, 1.03–5.41), and low HDL-C (2.19, 1.06–4.50). A similar, non-significant trend was observed for MASLD (1.83, 0.82–4.07). Conclusion The SPFQ has a strong relative validity for estimating UPF intake and suggests predictive utility for cardiometabolic outcomes.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an unhealthy lifestyle. However, there is limited prospective evidence regarding the association between combined lifestyle factors and MASLD. This study aims to test the association of a combination of lifestyle components, expressed as a healthy lifestyle index (HLI), and unhealthful eating behavior habits with MASLD, insulin resistance (IR), liver fibrosis, and metabolic dysfunction-associated steatohepatitis. METHODS:A prospective cohort study was conducted among participants of metabolic and hepatic screening surveys. MASLD was evaluated by ultrasonography or controlled attenuation parameter at 2 time points to assess new-onset, persistence, or remission, and IR was estimated by homeostasis model assessment. Presumed liver fibrosis and metabolic dysfunction-associated steatohepatitis were evaluated using FibroMax biomarkers. The HLI was calculated as the sum of 4 lifestyle components: nonsmoking, healthy weight, healthy diet, and physical activity. RESULTS:The final cohort included 315 subjects with 6.7 years of follow-up, 40-70 years old. In multivariable analyses, a favorable lifestyle (≥3 components) was independently associated with lower odds of new-onset MASLD (OR = 0.42; 95% CI: 0.19-0.90). Similarly, a favorable lifestyle was associated with lower odds of new-onset/persistent (vs. never/remission) MASLD and IR, respectively (OR = 0.49; 95% CI: 0.30-0.80; OR = 0.40; 95% CI: 0.24-0.66). There was a dose-response association between HLI and new-onset/persistent MASLD and IR. A favorable lifestyle was associated with lower odds of new-onset metabolic dysfunction-associated steatohepatitis (OR = 0.50; 95% CI: 0.27-0.95). Adjusting for HLI, unhealthful eating behavior habits were associated with higher odds of MASLD prevalence (OR = 1.81; 95% CI: 1.07-3.06). CONCLUSIONS:Adherence to a healthy lifestyle is prospectively associated with lower odds of MASLD, markers of liver damage, and IR. A holistic approach that considers overall lifestyle and eating behavior may be useful for preventing MASLD.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly related to nutrition. However, only a few human and animal studies have tested the association between MASLD and dairy consumption and the effect of milk fat on liver damage. Therefore, we aimed at testing the association between consumption of dairy product and the incidence of MASLD and fibrosis markers in humans, and the effect of milk fat vs. other fats on MASLD in animal studies. Methods: A prospective 7-year follow-up cohort study was performed including baseline and follow-up fasting blood tests, liver evaluation and a face-to-face interview on health status and behaviour using structured questionnaires. MASLD was determined by ultrasonography or by controlled attenuation parameter (CAP), and liver fibrosis by FibroTestTM TM or FibroScan (R). (R) . An animal study was performed in which 6-week-old C57BL/6j male mice were fed a high-fat diet (HFD) consisting of lard, soybean oil, and milk fat for 12 weeks. Metabolic impairment was assessed during the animal experiment, and serum advanced glycation end-products (AGEs) and liver damage were evaluated. Results: A total of 316 patients were included in the prospective cohort. In multivariable analysis, high consumption of low- medium fat low-sugar dairy products (g/day above the baseline sex-specific median) was associated with a lower risk for MASLD incidence (OR 0.42, 95% CI 0.18-0.95, p = 0.037) or incidence/persistence at follow-up (OR 0.58, 0.34-0.97, p = 0.039). Constantly high consumption of high-fat low-sugar dairy products was associated with greater odds for new onset/persistence of MASLD. Neither low-medium nor high-fat dairy consumption was related to fibrosis markers. In mice, all HFDs induced similar weight gain and steatosis and did not affect liver enzymes. Milk fat increases serum cholesterol and AGEs levels more than lard or soybean oil. Conclusions: Low-medium fat low-sugar dairy products may be protective and should be preferred over high-fat dairy to prevent MASLD. HFDs from different fat sources with a wide spectrum of fatty acid saturation content are equally deleterious. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objectives The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database. Methods A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015. A risk score was assigned according to the END-PAC model. Patients who developed PDAC over the 3-year period after NOD diagnosis were identified using the Israeli National Cancer Registry. Results Twenty-three percent (1245/5408) of NOD patients were classified as high-risk, of them 32 (2.6%) developed PDAC. Median follow-up time from NOD detection to PDAC diagnosis was 609 days (interquartile range, 367-997). The hazard ratio for PDAC diagnosis among individuals at the high-risk group compared with the low-risk group was 5.70 (95% confidence interval, 2.93-11.06). Using the high-risk group as the screening threshold, the sensitivity, specificity, positive predictive value and negative predictive value of the model were 54.2%, 76.98%, 2.57%, and 99.4%, respectively. Area under the curve of the model was 0.69. Conclusions Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.

Non-alcoholic fatty liver disease (NAFLD) has been associated with meat consumption in cross-sectional studies. However, only a few prospective studies have been conducted, and they did not test for liver fibrosis. We aimed to assess the association between meat consumption changes and the incidence and remission of NAFLD and significant liver fibrosis. We used a prospective cohort study design, including 316 subjects aged 40–70 years, participating in baseline and follow-up evaluations at Tel-Aviv Medical Center. NAFLD was determined by liver ultrasound or controlled attenuation parameter (CAP), and liver fibrosis was determined by FibroScan. Meat consumption (g/day) was assessed by a food frequency questionnaire (FFQ). In multivariable-adjusted analyses, high consumption of red and/or processed meat (≥gender-specific median) was associated with a higher risk of NAFLD with elevated alanine aminotransferase (ALT) (OR = 3.75, 1.21–11.62, p = 0.022). Consistently high (in both baseline and follow-up evaluations) total meat consumption was associated with 2.55-fold (95% CI 1.27–5.12, p = 0.009) greater odds for new onset and/or persistence of NAFLD compared to consistently low meat consumption. A similar association was shown for consistently high consumption of red and/or processed meat (OR = 2.12, 95% CI 1.11–4.05, p = 0.022). Consistently high red and/or processed meat consumption was associated with 4.77-fold (95% CI 1.36–16.69, p = 0.014) greater odds for significant fibrosis compared to consistently low consumption. Minimizing the consumption of red and/or processed meat may help prevent NAFLD and significant fibrosis.

Objectives The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database. Methods A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015. A risk score was assigned according to the END-PAC model. Patients who developed PDAC over the 3-year period after NOD diagnosis were identified using the Israeli National Cancer Registry. Results Twenty-three percent (1245/5408) of NOD patients were classified as high-risk, of them 32 (2.6%) developed PDAC. Median follow-up time from NOD detection to PDAC diagnosis was 609 days (interquartile range, 367–997). The hazard ratio for PDAC diagnosis among individuals at the high-risk group compared with the low-risk group was 5.70 (95% confidence interval, 2.93–11.06). Using the high-risk group as the screening threshold, the sensitivity, specificity, positive predictive value and negative predictive value of the model were 54.2%, 76.98%, 2.57%, and 99.4%, respectively. Area under the curve of the model was 0.69. Conclusions Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.

A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Background Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD. Methods Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months. Results Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis ( P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis ( P = 0.001). Conclusion Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population. Trial registration TRN NCT04561804 (9/17/2020)

BACKGROUND & AIMS:High consumption of ultra-processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non-alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related-liver damage.METHODS:A cross-sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non-invasive assessment of NASH and significant fibrosis. A food-frequency questionnaire was used to evaluate UPF consumption using the NOVA classification.RESULTS:A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31-2.71, P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07-2.19, P = .026; OR = 1.51, 1.08-2.11, P = .017; OR = 1.55, 1.05-2.29, P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07-3.38, P = .030; OR = 2.26, 1.20-4.26, P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03-3.45, P = .039; OR = 2.85, 1.14-7.14, P = .026 respectively).CONCLUSIONS:High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever-smoking may act synergistically with UPF to amplify the risk for fibrosis.

Background: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are associated with increased oxidative stress and lipid peroxidation, but large studies are lacking. The aim was to test the association of malondialdehyde (MDA), as a marker of oxidative damage of lipids, with NAFLD and liver damage markers, and to test the association between dietary vitamins E and C intake and MDA levels. Methods: A cross-sectional study was carried out among subjects who underwent blood tests including FibroMax for non-invasive assessment of NASH and fibrosis. MDA was evaluated by reaction with Thiobarbituric acid and HPLC-fluorescence detection method. NAFLD was diagnosed by abdominal ultrasound. Findings: MDA measurements were available for 394 subjects. In multivariate analysis, the odds for NAFLD were higher with the rise of MDA levels in a dose–response manner, adjusting for age, gender, BMI, and lifestyle factors. Only among men, higher serum MDA was associated of higher odds for NAFLD and NASH and/or fibrosis (OR = 2.59, 95% CI 1.33–5.07, P = 0.005; OR = 2.04, 1.02–4.06, P = 0.043, respectively). Higher vitamin E intake was associated with lower odds of high serum MDA level (OR = 0.28 95% CI 0.13–0.62, P = 0.002). In conclusion, serum MDA is associated with NAFLD and markers of NASH or fibrosis among men. Dietary vitamin E may be protective among women.

Background & Aims: The inverse association between non-alcoholic fatty liver disease (NAFLD) and diets rich in fruit and vegetables has been demonstrated, but the specific compounds that may be responsible for this association need to be elucidated. The aim of this studywas to test the association between phenolic acid consumption, NAFLD, and insulin resistance (IR). Methods: A cross-sectional cohort of individuals included in a metabolic screening program was studied. Liver steatosis was evaluated by ultrasonography and quantified by the hepatorenal index (HRI); fibrosis was assessed by FibroTest; IR by the sample upper quartile of the homeostatic model assessment score. Dietary intake was measured by a food frequency questionnaire. The phenolic acid content of food was calculated according to Phenol-Explorer. Results: A total of 789 individuals were included (52.6% men, age 58.83 +/- 6.58 years). Higher (above the upper median) phenolic acid intake was inversely associated with the presence of NAFLD (odds ratio [OR] 0.69; 95% CI 0.49-0.98; p = 0.036), higher HRI (OR 0.64; 95% CI 0.45-0.91; p = 0.013) and higher IR (OR 0.61; 95% CI 0.42-0.87; p = 0.007), when adjusted for age, gender, body mass index, and lifestyle factors. Considering specific classes of phenolic acids, higher hydroxybenzoic acid intake was independently associated with lower odds of NAFLD, higher HRI and fibrosis. Higher hydroxycinnamic acid intake was independently associated with lower odds of IR. Conclusion: A higher intake of phenolic acids is associated with a lower prevalence of liver steatosis and IR in a crosssectional study, suggesting a possible protective effect that requires confirmation in prospective studies. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

Nonalcoholic fatty liver disease (NAFLD) is characterized by substantial diagnostic and evaluation gaps with no systematic screening. Even recognized cases are undercoded because of the perceived benign nature of disease and current absence of approved pharmacologic treatment. NAFLD is often detected incidentally, particularly in the asymptomatic early phase. We doubled NAFLD detection via natural language processing of 1 million imaging reports combined with laboratory data from an unselected population. We describe NAFLD comorbidities and health care utilization as compared with age, sex, and body mass index matched control subjects.

Abstract Background: Budd-Chiari syndrome (BCS) is a rare disease defined as hepatic venous outflow obstruction at any level from the hepatic venules up to the cavo-atrial junction. Transjugular Intrahepatic Portosystemic Shunt (TIPS) is performed as a decompressive treatment in some patients.Aim: To evaluate the potential role of Transient Elastography (TE) in assessing liver stiffness in patients with primary BCS.Methods: Twenty one BCS patients and 10 patients with liver cirrhosis with different underlying etiologies underwent abdominal ultrasound and TE.Results: Ninety-five percent of BCS patients had liver stiffness compatible with F4 with a median of 21 kPa, values which are usually obtained in patients with liver cirrhosis. Ten BCS and 10 cirrhotic patients underwent repeated TE with a median of 320 days between exams for BCS and 4.5 years for cirrhotic patients. The change of liver stiffness in BCS patients was 5.75 kPa (range − 0.4 to 26.6), compared with − 4.85 kPa (range − 15.6 to 15.0) in cirrhotic patients (p-value = 0.0029). Change in liver stiffness from baseline to follow-up in BCS patients who underwent TIPS (n = 4) was 0.2 kPa (range − 0.4 to 15.3), whereas in patients without intervention (n = 6) it was 6.75 kPa (range 1.3 to 26.6). The difference was not statistically significant.Conclusion: Liver stiffness in BCS patients is a dynamic progressive process with parameters of TE resembling liver cirrhosis. Even if TIPS seem to slow down the increment of liver stiffness, because of decreased liver congestion, it kept most patients with high score. The TE in BCS patients may be considered for monitoring for stable or upfront disease deterioration.

Background & aims: Although antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers. Methods: Cross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis >= F1-F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ). Results: Overall, 789 subjects were included (52.6% men, age 58.83 +/- 6.58 years), 714 had reliable Fibro-Max. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43-0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30-0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47-0.99, P = 0.045; OR = 0.57, 0.38-0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest. Conclusion: Vitamin E and C intake may be protective from NAFLD-related liver damage. (c) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be positively associated with serum advanced glycation end products (AGEs) and negatively with soluble receptor for AGE (sRAGE) in a few small studies. We aimed to test the association between lifestyle and sRAGE levels and the association between sRAGE levels or AGEs intake and NAFLD, insulin resistance (IR), and elevated alanine aminotransferase (ALT). METHODS: Cross-sectional analysis among participants of a screening study. Fasting blood tests and serum sRAGE levels were obtained. NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment, respectively. Nutritional intake was measured by food frequency questionnaire, and the intake of dietary AGEs was calculated. RESULTS: A total of 743 subjects were included (52.6% men, mean age 58.83 ± 6.58 years, 38.7% NAFLD). Exercise was independently protective from low sRAGE levels (odds ratio [OR] = 0.71, 95% confidence interval 0.52–0.97, P = 0.031). Pack-years, working time, and sedentary time (OR = 1.51, 1.03–2.22, P = 0.036; OR = 1.66, 1.18–2.35, P = 0.004; OR = 1.64, 1.18–2.29, P = 0.004, respectively), and intake of red and/or processed meat or processed meat alone (OR = 1.01, 1.04–2.21, P = 0.045; OR = 1.49, 1.00–2.21, P = 0.048, respectively) were associated with increased odds for low sRAGE levels. Low sRAGE levels were independently associated with elevated ALT (OR = 1.69, 1.11–2.57, P = 0.014) and NAFLD with elevated ALT (OR = 2.17, 1.23–3.83, P = 0.007). High intake of dietary AGEs was associated with IR (OR = 2.04, 1.25–3.34 P = 0.004). DISCUSSION: Lifestyle is associated with sRAGE levels and, in turn, low levels of sRAGE are associated with NAFLD and elevated ALT.

Longitudinal assessment of body composition following bariatric surgery allows monitoring of health status. Our aim was to elucidate trends of anthropometric and clinical outcomes 3 years following sleeve gastrectomy (SG). A prospective cohort study of 60 patients who underwent SG. Anthropometrics including body composition analysis measured by multi-frequency bioelectrical impedance analysis, blood tests, liver fat content measured by abdominal ultrasound and habitual physical activity were evaluated at baseline and at 6 (M6), 12 (M12), and 36 (M36) months post-surgery. Sixty patients (55% women, age 44.7 ± 8.7 years) who completed the entire follow-up were included. Fat mass (FM) was reduced significantly 1 year post-surgery (55.8 ± 11.3 to 26.7 ± 8.3 kg; P < 0.001) and then increased between 1 and 3 years post-operatively, but remained below baseline level (26.7 ± 8.3 to 33.1 ± 11.1 kg; P < 0.001). Fat free mass (FFM) decreased significantly during the first 6 months (64.7 ± 14.3 to 56.9 ± 11.8 kg; P < 0.001), slightly decreased between M6 and M12 and then reached a plateau through M36. Weight loss “failure” (< 50% excess weight loss) was noticed in 5.0% and 28.3% of patients at M12 and M36, respectively. Markers of lipid and glucose metabolism changed thereafter in parallel to the changes observed in FM, with the exception of HDL-C, which increased continuingly from M6 throughout the whole period analyzed (45.0 ± 10.2 to 59.5 ± 15.4 mg/dl; P < 0.001) and HbA1c which continued to decrease between M12 and M36 (5.5 ± 0.4 to 5.3 ± 0.4%; P < 0.001). There were marked within-person variations in trends of anthropometric and clinical parameters during the 3-year follow-up. Weight regain primarily attributed to FM with no further decrease in FFM occurs between 1 and 3 years post-SG. FM increase at mid-term may underlie the recurrence of metabolic risk factors and can govern clinical interventions.