Lifestyle Modification: Evaluation of the Effects of Physical Activity and Low-Glycemic-Index Mediterranean Diet on Fibrosis Score.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one the most prevalent causes of chronic liver disease worldwide. In the absence of an approved drug treatment, lifestyle modification is the first intervention strategy. This study aimed to estimate the main effect of two different physical activity (PA) programs, and a Low-Glycemic-Index Mediterranean Diet (LGIMD), or their combined effect on liver fibrosis parameters in subjects with NAFLD. METHODS: Subjects with moderate or severe NAFLD grade of severity (n = 144) were randomly assigned to six intervention arms for three months: LGIMD, PA programs, and their combination. Data were collected at baseline, 45 days, and 90 days. Transient elastography was performed to assess the outcome. RESULTS: at 90 days, a statistically significant reduction in kPa was found among subjects following LGMID (-2.85, 95% CI -5.24, -0.45) and those following an LGIMD plus PA1 (-2.37, 95% CI -4.39, -0.35) and LGIMD plus Pa2 (-2.21, 95% CI -4.10, -0.32). The contrast between time 2 and time 1 of the LGIMD plus PA2 treatment showed a statistically significant increase, and vice versa: the contrast between time 3 and time 2 of the same treatment showed a statistically significant reduction. The PA1 and PA2 arms also showed reduced kPa, although the results did not reach statistical significance. CONCLUSIONS: The intervention arms, LGIMD, LGIMD+PA1, and LGIMD+PA2, reduced the fibrosis score.

Diet and Exercise Exert a Differential Effect on Glucose Metabolism Markers According to the Degree of NAFLD Severity.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes (T2D) are highly prevalent diseases worldwide. Insulin Resistance (IR) is the common denominator of the two conditions even if the precise timing of onset is unknown. Lifestyle change remains the most effective treatment to manage NAFLD. This study aimed to estimate the effect of the Low Glycemic Index Mediterranean Diet (LGIMD) and exercise (aerobic and resistance) over a one-year period on the longitudinal trajectories of glucose metabolism regulatory pathways. MATERIALS AND METHODS: In this observational study, 58 subjects (aged 18-65) with different degrees of NAFLD severity were enrolled by the National Institute of Gastroenterology-IRCCS "S. de Bellis", to follow a 12-month program of combined exercise and diet. RESULTS: The mean age was 55 ± 7 years old. Gender was equally distributed among NAFLD categories. There was a statistically significant main effect of time for glycosylated hemoglobin (Hb1Ac) over the whole period (-5.41, 95% CI: -7.51; -3.32). There was a steady, statistically significant decrease of HbA1c in participants with moderate and severe NAFLD whereas this effect was observed after the 9th month in those with mild NAFLD. CONCLUSIONS: The proposed program significantly improves glucose metabolism parameters, especially HbA1c.

The Effect of Low Glycemic Index Mediterranean Diet and Combined Exercise Program on Metabolic-Associated Fatty Liver Disease: A Joint Modeling Approach.

BACKGROUND: Excessive caloric intake and reduced energy expenditure are associated with the onset of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to probe the benefits of a low glycemic index Mediterranean diet (LGIMD) and a combined exercise program (CEP) on MAFLD by monitoring the clinical process through anthropometric measurement, body mass index (BMI), and specific biomarkers, such as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). METHODS: The study was conducted at the National Institute of Gastroenterology, 'S. de Bellis', Italy. Subjects were invited to join the study for 12 months. RESULTS: 54 participants were enrolled. Joint modeling of longitudinal and time-to-event data was applied. Overall, a statistically significant direct effect of LGIMD/CEP adherence on ln (BMI), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a strong statistically significant direct effect of log (BMI) on time-to-event were observed. In addition, a statistically significant direct effect of LGIMD/CEP adherence on ln(HOMA-IR), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a statistically significant direct effect of ln(HOMA-IR) on time-to-event were observed. CONCLUSIONS: LGIMD/CEP significantly improved MAFLD status; in addition, longitudinal BMI and HOMA-IR were good predictors of the disappearance of diagnostic criteria for MAFLD.

Effects of weight change on all causes, digestive system and other causes mortality in Southern Italy: a competing risk approach.

Weight change is associated with all causes of death, cardiovascular, and cancer mortality and a heterogeneous group of other causes of death. We aimed to estimate the effect of weight change on all causes and cause-specific mortality in a cohort with a high prevalence of deaths due to diseases of the digestive system.MethodsIn this prospective cohort study, 2230 subjects aged 30 to 50 years were examined. The study consisted of a 32-year longitudinal study period (January 1985 to December 2017) and mortality follow-up. Outcomes were mortality from all causes and deaths from gastrointestinal disease. Root Mean Squared Error (RMSE) was evaluated to capture individual residual variation in Body Mass Index (BMI) after adjustment for baseline BMI, and the relationship of residual variation with mortality was calculated as cumulative incidence function and cause-specific hazard (CSH) rate.ResultsIn total, 793 participants died during the follow-up, 96 of them due to Digestive system causes. Magnitude of residual variation weight in the last quintile was associated with all-cause mortality (relative risk, 2.00; 95% CI, 1.54-2.59) and Digestive system causes (relative risk, 3.82; 95% CI, 1.86-7.81).ConclusionThe findings suggest an association between weight change and gastrointestinal disease mortality. Epidemiological works studying the correlation between weight change and mortality should consider this aspect.

Modified WCRF/AICR Score and All-Cause, Digestive System, Cardiovascular, Cancer and Other-Cause-Related Mortality: A Competing Risk Analysis of Two Cohort Studies Conducted in Southern Italy.

BACKGROUND: In real life, nutrition goes beyond purely biological domains. Primary prevention is the most efficient approach for reducing the risk of mortality. We aimed to study the association of lifestyle, as measured by a modified World Cancer Research Fund/American Institute for Cancer Research (mWCRF/AICR) scoring system with all-cause, digestive system disease-related (DSD-related), cardiovascular disease-related (CVD-related), cancer-related and other cause-related mortality using data from two population-based cohort studies conducted in Southern Italy. METHODS: A random sample of 5271 subjects aged 18 years or older was enrolled in 2005-2006 and followed up until 2020. Usual food intakes were estimated using a validated dietary questionnaire. Competing risks survival models were applied. RESULTS: High adherence to the mWCRF/AICR score was found to be statistically significant and negatively associated with all-cause mortality (HR 0.56, 95%CI 0.39; 0.82), DSD-related mortality (SHR 0.38, 95%CI 0.15; 0.97) and cancer-related mortality (SHR 0.43, 95%CI 0.19; 0.97) in the male sub-cohort and other-cause mortality (SHR 0.43, 95%CI 0.21; 0.88) only in the female group. CONCLUSIONS: This mWCRF/AICR score can be seen as a simple, easy tool for use in clinical practice to evaluate both qualitative and quantitative aspects of the diet.

Development and validation of a neural network for NAFLD diagnosis.

Non-Alcoholic Fatty Liver Disease (NAFLD) affects about 20-30% of the adult population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Liver ultrasound (US) is widely used as a noninvasive method to diagnose NAFLD. However, the intensive use of US is not cost-effective and increases the burden on the healthcare system. Electronic medical records facilitate large-scale epidemiological studies and, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Our goal was to develop and validate a simple Neural Network (NN)-based web app that could be used to predict NAFLD particularly its absence. The study included 2970 subjects; training and testing of the neural network using a train-test-split approach was done on 2869 of them. From another population consisting of 2301 subjects, a further 100 subjects were randomly extracted to test the web app. A search was made to find the best parameters for the NN and then this NN was exported for incorporation into a local web app. The percentage of accuracy, area under the ROC curve, confusion matrix, Positive (PPV) and Negative Predicted Value (NPV) values, precision, recall and f1-score were verified. After that, Explainability (XAI) was analyzed to understand the diagnostic reasoning of the NN. Finally, in the local web app, the specificity and sensitivity values were checked. The NN achieved a percentage of accuracy during testing of 77.0%, with an area under the ROC curve value of 0.82. Thus, in the web app the NN evidenced to achieve good results, with a specificity of 1.00 and sensitivity of 0.73. The described approach can be used to support NAFLD diagnosis, reducing healthcare costs. The NN-based web app is easy to apply and the required parameters are easily found in healthcare databases.

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications. The present review is aimed to discuss on cellular and metabolic alterations associated with NAFLD, which can be helpful to identify new noninvasive biomarkers. The identification of accumulated lipids in the cell membranes, as well as circulating cytokeratins and exosomes, provides new insights in understanding of NAFLD. This review also suggests that lifestyle modifications remain the main prevention and/or treatment for NAFLD.

Decreased levels of physical activity: results from a cross-sectional study in southern Italy during the COVID-19 lockdown.

BACKGROUND: During the COVID-19 pandemic, the Italian government took security measures to try to limit infections. Restrictive measures included social distancing, home confinement and the closure of all public structures like gyms and swimming pools. The impact of these limitations on health and lifestyle was inevitably negative. The purpose of this study was to establish the level of physical activity (PA), expressed as energy expenditure (MET-minute/week) in a Southern Italian population before and during the COVID-19 lockdown. METHODS: An adapted version of the International Physical Activity Questionnaire-short form (IPAQ-SF) was published on the official website of the National Institute of Gastroenterology IRCCS S. de Bellis, Castellana Grotte, Bari, Italy and on several social media in May 2020. RESULTS: Three hundred ten replies (72% women) from Apulia (60%), Calabria (28%), Campania (11%) and Sicily (1%) were included in the study. The COVID-19 lockdown had a negative effect on the vigorous PA intensity level and on walking, but not on the moderate PA intensity level. Additionally, daily time spent sitting down increased by more than 12% during the COVID-19 lockdown. CONCLUSIONS: Isolation changed PA behaviors. The decreased energy expenditure (MET-minute/week) during the lockdown had a negative impact in both genders, especially on the young adults and adults' groups.

The effect of the Mediterranean Diet on lifespan: a treatment-effect survival analysis of a population-based prospective cohort study in Southern Italy.

BACKGROUND: The Mediterranean diet (MedDiet) is associated with good health. We aimed to estimate the effect of levels of adherence to the MedDiet on lifespan by performing treatment effects survival analysis. METHODS: A sample of 5250 subjects aged ≥18 years were randomly selected from the electoral list of Castellana Grotte and Putignano (Apulian Region, Italy). Cohorts were enrolled in 2005-06 and followed-up until December 2018. The adherence to the MedDiet was measured by the relative Mediterranean score (rMED) and categorized as high, medium and low. Time-to-death (all-causes) as estimated by average treatment effect on the treated (ATET), potential outcome mean (POM) and relative efficiency of exposure were the outcomes. RESULTS: A total of 4896 subjects were included. The median follow-up time was 12.82 (inter quartile range (IQR) 12.22-13.05), 12.91 (IQR 12.21-13.27) and 12.84 (IQR 12.19-13.03) years for high, medium and low rMED subjects respectively. By December 2018, 453 (9.25%) had died. There was a strong effect of medium and low rMED {ATET, -5.10 [95% confidence interval (CI) -9.39, -0.80] and -8.91 (95%CI -13.37, -4.45), respectively}. High rMED has an important effect on mean age at death [POM 90.16 (95% CI 86.06, 94.25)]. The relative effect size for medium and low rMED subjects was a lower lifespan of 5.62% (95% CI 1.01, 10.3) and 9.90% (95% CI 5.30, 5.30), respectively. CONCLUSIONS: We observed an important benefit in additional years of survival from adherence to MedDiet in this southern Italian cohort. Further investigation corroborating our findings in other population groups in other geographic regions will be an important contribution to promoting health and longevity.

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide, and lifestyle modification is the current standard treatment. The aim of the study was to estimate the effect of two different physical activity (PA) programs, a Low Glycemic Index Mediterranean Diet (LGIMD), and their combined effect on the NAFLD score as measured by FibroScan®. METHODS: Moderate or severe NAFLD subjects (n = 144) were randomly assigned to six intervention arms during three months. Interventions arms were a control diet, LGIMD, aerobic activity program (PA1), combined activity program (PA2), and LGIMD plus PA1 or LGIMD plus PA2. The data were compared at baseline, at 45 days, and at 90 days. Analysis of variance was performed under the intention-to-treat principle. RESULTS: There was a statistically significant reduction in the NAFLD score after 45 days of treatment in every working arm except for Arm 1 (control diet). After 90 days, the best results were shown by the intervention arms in which LGIMD was associated with PA: LGIMD plus PA1 (-61.56 95% CI -89.61, -33.50) and LGIMD plus PA2 (-38.15 95% CI -64.53, -11.77). CONCLUSION: All treatments were effective to reduce NAFLD scores, but LGIMD plus PA1 was the most efficient.

Selecting the best machine learning algorithm to support the diagnosis of Non-Alcoholic Fatty Liver Disease: A meta learner study.

BACKGROUND & AIMS: Liver ultrasound scan (US) use in diagnosing Non-Alcoholic Fatty Liver Disease (NAFLD) causes costs and waiting lists overloads. We aimed to compare various Machine learning algorithms with a Meta learner approach to find the best of these as a predictor of NAFLD. METHODS: The study included 2970 subjects, 2920 constituting the training set and 50, randomly selected, used in the test phase, performing cross-validation. The best predictors were combined to create three models: 1) FLI plus GLUCOSE plus SEX plus AGE, 2) AVI plus GLUCOSE plus GGT plus SEX plus AGE, 3) BRI plus GLUCOSE plus GGT plus SEX plus AGE. Eight machine learning algorithms were trained with the predictors of each of the three models created. For these algorithms, the percent accuracy, variance and percent weight were compared. RESULTS: The SVM algorithm performed better with all models. Model 1 had 68% accuracy, with 1% variance and an algorithm weight of 27.35; Model 2 had 68% accuracy, with 1% variance and an algorithm weight of 33.62 and Model 3 had 77% accuracy, with 1% variance and an algorithm weight of 34.70. Model 2 was the most performing, composed of AVI plus GLUCOSE plus GGT plus SEX plus AGE, despite a lower percentage of accuracy. CONCLUSION: A Machine Learning approach can support NAFLD diagnosis and reduce health costs. The SVM algorithm is easy to apply and the necessary parameters are easily retrieved in databases.

Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.

BACKGROUND AND AIMS: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

The Effect of Three Mediterranean Diets on Remnant Cholesterol and Non-Alcoholic Fatty Liver Disease: A Secondary Analysis.

BACKGROUND: Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. METHODS: This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol-low density lipoprotein cholesterol (LDL-C)-high density lipoprotein cholesterol (HDL-C)]. RESULTS: REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. CONCLUSIONS: fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.

Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study.

Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95-0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34-0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74-0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01-1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01-1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01-1.21), fats (O.R. 1.12, 95% C.I. 1.01-1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.

Effectiveness of two physical activity programs on non-alcoholic fatty liver disease. a randomized controlled clinical trial.

Introduction: To estimate the effectiveness of two physical activity programs on NAFLD. Methods: Participants come from a survey conducted in southern Italy. Subjects with moderate or severe NAFLD were invited to participate. After giving informed consent, they completed a questionnaire, underwent ultrasonography and anthropometric measurements. Then they were randomized an Aerobic or a Combined Exercise program and followed up for six months. The first group followed a program of moderate aerobic activity lasting 30 minutes, 5 days per week. The second group did aerobic training with the addition of muscle training involving the large muscle groups, stimulating them to make more intense efforts, for a duration of 60 minutes, at least, 3 days a week. Compliance with the programs was measured. A mixed linear model was applied to the data. Results: Compliance with Aerobic Exercise was homogeneous and increased over time. Combined Program compliance was equal to 100%. There was no significant difference in the NAFLD mean score by treatment at baseline and after six months. However, there was a significant reduction in the NAFLD mean score for treatments after six months. The NAFLD measured score was reduced by 22% in the Aerobic treatment group when confronted with the other program. In the Combined program, after 6 months, results showed to be less effective than the Aerobic Exercise in reducing the NAFLD score. Conclusion: An aerobic exercise program is a realistic intervention which could be included as a part of primary prevention of several chronic diseases.

Introducción: Estimar la eficiencia de dos programas de actividad física sobre la NAFLD Métodos: Sujetos con NAFLD moderada o severa que habían participado a un estudio de pobación en el sur de Italia fueron invitados a participar. Fue completado un cuestionario, se tomaron medidas antropométricas y se realizó una ecografia hepática. Cada participante proveyó el consenso informato. Los participantes fueron aleatorizados a un programa aerobico (actividad aerobica moderada per 30 minutos, 5 veces a la semana) o un programa mixto (aerobico más entrenamiento de la fuerza de los grandes grupos musculares, 60 minutos, tres veces a la semana). Fue medida la adherencia a los programas y se aplicó un modelo linear mixto a los datos. Resultados: El programa aerobico tuvo muy buena adherencia y esta aumentó con el tiempo mientras el programa mixto tuvo 100% de adherencia. No hubo diferencias estadísticamente significativas en el score de NAFLD al enrolamiento, mientras hubo diferencias estadísticamente significativas en el score medio de NAFLD después de 6 meses pero el score en el grupo del programa aerobico tuvo una reducción del 22% más intensa que el programa mixto. Este último programa por lo tanto se ha mostrado menos efectivo que el programa aerobico. Conclusión: Un programa de actividad física aerobica es un tratamiento realístico que podría ser efectuado no solo para la NAFLD sino también como prevención primaria de otras enfermedades crónicas.

Reducing NAFLD-screening time: A comparative study of eight diagnostic methods offering an alternative to ultrasound scans.

BACKGROUND & AIMS: The use of ultrasound scan (US) in non-alcoholic fatty liver disease (NAFLD) screening overloads US waiting lists. We hypothesized and tested a hybrid two-step method, consisting of applying a formula, to exclude subjects at low risk, before US. METHODS: The sample included 2970 males and females (937 with NAFLD) diagnosed by US. We selected eight formulas: Fatty Liver Index (FLI), Hepatic Steatosis Index (HIS), body mass index (BMI), waist circumference (WC), Abdominal Volume Index (AVI), waist-to-height ratio (WHtR), waist/height0.5 (WHT.5R) and Body Roundness Index (BRI), and calculated their performance in the two-step method evaluating percentage reduction of the number of liver US (US reduction percentage), percentage of false negative and percentage of NAFLD identified. RESULTS: The US reductions percentage were 52.2% (WHtR), 52.1% (HIS), 51.8% (FLI), 50.8% (BRI), 50.7% (BMI and WHt_5R), 46.5% (WC) and 45.2% (AVI). The false negative percentage were 8.5% (WHtR), 7.9% (BRI), 7.3% (WHt_5R), 7.2% (BMI), 6.7% (HIS), 6.6% (FLI), 5.6% (WC) and 5.2% (AVI). The best percentage of NALFD identified was obtained using AVI (83.6%) before US, then WC (82.2%), FLI (79%), HIS (78.9%), BMI (77.3%), WHt_5R (76.9%), BRI (74.8%) and WHtR (73%). CONCLUSION: The best formula to use in two-step diagnostic NAFLD screening was AVI, which showed a low false negative rate and a higher percentage of identified NAFLD. Other studies evaluating the economic advantages of this screening method are warranted.

Aerobic Physical Activity and a Low Glycemic Diet Reduce the AA/EPA Ratio in Red Blood Cell Membranes of Patients with NAFLD.

Omega-6 Polyunsaturated Fatty Acids (PUFAs), through the eicosanoids derived from arachidonic acid (AA), are able to modulate the inflammatory processes, whereas omega-3 PUFAs, such as eicosapentaenoic acid (EPA), exert anti-oxidant and anti-inflammatory effects. An unbalanced AA/EPA ratio in favor of AA leads to the development of different metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effects of different diets, alone and in combination with two physical activity programs, on the AA/EPA ratio value in erythrocyte membranes of patients with NAFLD. One hundred forty-two subjects with NAFLD were enrolled in the study and randomized into six treatment groups. AA/EPA ratio was significantly reduced after 90 days of treatment with only a program of aerobic activity. However, it appears that the combination of physical activity and a Low Glycemic Index Mediterranean Diet (LGIMD) was more efficacious in reducing AA/EPA levels, at 45 days of treatment, even if this effect was not maintained over time. The combined effect of diet and physical activity reduced the AA/EPA ratio value improving the score of steatosis. Dietary intake of omega-3 PUFAs, in association with a healthy lifestyle, may be used in the prevention protocols for many chronic diseases, including NAFLD.

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. METHODS: This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. RESULTS: The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. CONCLUSIONS: Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.