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In this placebo-controlled, randomized trial of pioglitazone in subjects with nonalcoholic steatohepatitis, pioglitazone was associated with improvements in the results of liver-function tests, hepatic fat content, and hepatic insulin sensitivity. As compared with placebo, pioglitazone significantly reduced the histologic abnormalities of steatohepatitis but did not significantly reduce fibrosis. In subjects with nonalcoholic steatohepatitis, pioglitazone was associated with improvements in the results of liver-function tests, hepatic fat content, and hepatic insulin sensitivity. Pioglitazone significantly reduced the histologic abnormalities of steatohepatitis but did not significantly reduce fibrosis. Nonalcoholic steatohepatitis, a chronic liver condition that may progress to cirrhosis, is characterized by insulin resistance, the accumulation of hepatic fat, and predominantly lobular necroinflammation, with or without centrilobular fibrosis. The disorder is thought to be common, since the incidence of its typical features — fatty liver disease, obesity, and type 2 diabetes mellitus — is increasing. 1 Weight loss remains the standard of care because no pharmacologic therapy has conclusively proved to be effective for the treatment of this condition. Multiple pharmacologic interventions have been attempted with variable success; these include pentoxifilline, 2 orlistat, 3 vitamin E, 4 – 6 ursodeoxycholic acid, 7 and lipid-lowering . . .

Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P<0·05). BMI, waist circumference, serum aspartate aminotransferase, bilirubin, HDL-cholesterol and apo a1 were reduced significantly in both groups (P<0·05); however, there were no significant differences between the two groups (P>0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), and although calorie restriction is recommended in guidelines, but adherence is an issue. The current study aimed to determine the effectiveness of eight weeks intermittent fasting (IF) strategy in the control of NAFLD activity and the adherence rate of such strategy. This was a randomized controlled trial with modified alternate-day calorie restriction (MACR), a form of IF, as the active intervention and usual habitual diet as control. The outcome measures included changes in body mass index (BMI), blood lipids (cholesterol, LDL, HDL and triglyceride), fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasound measurements of liver steatosis and 2-dimensional shear wave elastography (SWE). Per-protocol (PP) analysis was performed with comparison within (post vs. pre-intervention) and between (MACR vs. control) groups and P < 0.05 as significant. Of 115 individuals with NAFLD, 43 satisfied the study entry criteria, and 33 were randomised to MACR and 10 to control group, and after 8 weeks, 30 from MACR and 9 from control group completed PP. Significant reduction in weight and BMI (P = 0.001 and 0.02 respectively) was observed in MACR vs. control. Likewise, ALT was reduced with MACR but not control (P = 0.02). No reductions in lipid parameters and FBS were found in between-group analyses (all P > 0.22). Both liver steatosis and fibrosis (SWE) scores were significantly reduced in MACR vs. controls (both P < 0.01). Adherence level for MACR remained between 75-83% throughout the study. As a conclusion, eight weeks of IF (MACR) strategy appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from “nonalcoholic fatty liver disease” (NAFLD) to “metabolic dysfunction-associated fatty liver disease” (MAFLD) and, finally, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut–liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.

Plant-based diets (PBDs) are gaining attention as a sustainable and health-conscious alternative for managing various chronic conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). In the absence of pharmacological treatments, exploring the potential of lifestyle modifications to improve biochemical and pathological outcomes becomes crucial. The adoption of PBDs has demonstrated beneficial effects such as weight control, increased metabolic health and improved coexisting diseases. Nonetheless, challenges persist, including adherence difficulties, ensuring nutritional adequacy, and addressing potential deficiencies. The aim of this review is to provide a comprehensive overview of the impact of PBDs on MASLD, emphasizing the need for tailored dietary interventions with professional support to optimize their effectiveness in preventing and treating metabolic diseases.

IntroductionMetabolic associated fatty liver disease (MAFLD) is internationally prevalent, resulting in considerable health and economic costs. Lifestyle adjustments, especially exercise, constitute fundamental treatments; nonetheless, sustained adherence poses significant challenges. This study is to assess the effectiveness of a 12-week digital exercise intervention in decreasing liver fat and enhancing metabolic outcomes in individuals with MAFLD.Methods and analysisThis pragmatic, investigator-initiated study is a stratified, randomised controlled parallel-group clinical trial. Participants meeting the enrolment criteria will be stratified and randomised based on exercise habits and risk levels. They will be allocated into either the intervention group or the active-control group,with 50 participants per group. Participants in the intervention group will undergo a 12-week digital platform-based exercise intervention customised to their activity risk classification, encompassing exercise monitoring, dietary intervention and health education. Simultaneously, the active-control group will receive traditional exercise monitoring, dietary intervention and health education after the development of their health plan. The primary outcome measure will be liver fat fraction measured by magnetic resonance imaging-proton density fat fraction. Secondary outcome measures will encompass body composition, blood pressure, body weight, body mass index, blood lipids, liver function and additional factors. Evaluations will be performed at baseline and after the intervention (12 weeks).Ethics and disseminationEthical approval of this trial was granted by the ethics committee of the First Affiliated Hospital of Nanjing Medical University (2024-SR-167). Informed written consent will be acquired from study participants prior to enrolment. The results will be published in peer-reviewed journals.Trial registration numberChiCTR2400083477.

Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs—inulin-type fructans) (n = 8) or placebo (maltodextrin) (n = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by H1MRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of Bifidobacterium (p = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests’ metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD.

INTRODUCTION:Obesity is the primary cause of metabolic dysfunction-associated steatotic liver disease (MASLD). Healthy lifestyle management has potential value in the treatment of MASLD.METHODS:A total of 150 patients with MASLD diagnosed at the Health Management Center of our hospital were enrolled and randomly divided into a traditional treatment (control group, n = 75) and a healthy lifestyle group (observation group, n = 75). All patients underwent a 3-month intervention. Data on general information, body composition, glucose metabolism, lipid metabolism, and inflammatory factors were analyzed.RESULTS:The difference in the change in fatty liver grade was statistically significant (P < 0.05). There were statistically significant differences in treatment efficiency for physical conditions (P < 0.05), including body fat mass, body mass index, body weight, waist circumference, and waist-to-hip ratio. In addition, there were statistically significant differences in treatment efficiency for scales such as the Diet Rating Scale, Emotional Stress Scale, and Global Physical Activity Questionnaire (P < 0.05). Differences in treatment efficiency for body fat parameters, including percentage of body fat, visceral fat area, aspartate aminotransferase, and diastolic blood pressure, were also statistically significant (P < 0.05). After treatment, statistically significant differences were observed in interferon-γ, insulin, low-density lipoprotein cholesterol, triglycerides, and tumor necrosis factor-α (P < 0.05).DISCUSSION:Our study indicates that a healthy lifestyle can effectively promote the reduction of fatty liver grade in patients with MASLD, demonstrating positive effects in improving lipid metabolism and inflammatory responses in these patients.

Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin versus prescriptive diet or vitamin E. In an open label, randomized trial, nondiabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12 months. The control cases were given either vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology. Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (p < 0.0001), and alanine aminotransferase normalized in 56% of cases (odds ratio (OR) versus. controls, 3.11; 95% confidence interval (CI), 1.56-6.20; p= 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases, and change in body mass index (OR, 5.98; 95% CI, 2.05-17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (p= 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 nonresponders) showed a significant decrease in liver fat (p= 0.0004), necroinflammation, and fibrosis (p= 0.012 for both). No side effects were observed during metformin treatment. Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings, which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.