This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0–F1; n = 30) and NASH with significant fibrosis (stage F2–F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2–F4 than those with NASH with F0–F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2–4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity. Full article

Background and Aims: Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, hepatic injury being of concern in these patients. Current literature reports an increased prevalence of liver steatosis and fibrosis in subjects with IBD and the pathophysiology is yet to be completely understood. The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with IBD, as well as to determine the factors that connect these two disorders. Methods: From September 2021 to June 2022, 82 consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter (CAP) was used to assess the presence of NAFLD, with a cut-off score for CAP of 248 dB/m. Significant liver fibrosis was considered at a cut-off for liver stiffness measurements (LSM) of 7.2 kPa. Results: In total, 82 IBD patients (54.8% men, mean age of 49 ± 13 years) were included, 38 (46.3%) of them being diagnosed with NAFLD, with a mean CAP score of 286 ± 35.4 vs. 203 ± 29.7 in patients with IBD only. Age (β = 0.357, p = 0.021), body mass index (BMI) (β = 0.185, p = 0.048), disease duration (β = 0.297, p = 0.041), C—reactive protein (β = 0.321, p = 0.013), fasting plasma glucose (β = 0.269, p = 0.038), and triglycerides (β = 0.273, p = 0.023) were strongly associated with the presence of liver steatosis. The multivariate analysis showed that older age, BMI, and disease duration were strongly associated with significant liver fibrosis in our group. Conclusions: NAFLD is a multifaced pathology with growing prevalence among IBD patients. Additional studies are needed to completely understand this problem and to create a solid evidence-based framework for more effective preventative and intervention strategies. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disease, characterized by fatty acids liver accumulation and subsequent fibrosis. NAFLD prevalence ranges from 80% to 90% in obese subjects and is estimated to be around 50% in patients with metabolic syndrome. In this clinical scenario, diet and lifestyle modifications can play an important role. There are several imaging techniques that can accurately diagnose fatty liver. Recently, ultrasound has acquired a leading role in the diagnosis and follow-up of fatty liver disease. Furthermore, elastosonography represents a valid alternative to liver biopsy. Shear wave elastosonography evaluates the elastic and mechanical properties of liver tissue. The aim is to evaluate the effects of lifestyle and nutritional interventions and a loss of body weight during hepatic steatosis through ultrasonographic and elastosonographic techniques. Thirty-two female subjects with metabolic syndrome were subjected to clinical, anthropometric, and laboratory assessments, as well as abdominal ultrasonographic/elastosonographic measurements taken from enrollment time (T0) and after 3 months (T1) of lifestyle modifications. After 3 months of lifestyle changes, significant weight loss was observed, with a marked improvement in all adiposity indices. The laboratory parameters at T1 showed significant decreases in total and LDL cholesterol, triglycerides, basal blood glucose, 120 min glycaemia, basal insulin and HOMA Index (p < 0.001). A similar improvement was observed at T1 for steatosis degree (p < 0.01) and elastosonographic measurements (Kpa p < 0.001). The linear regression analysis of the baseline conditions documented that the size of the liver positively correlated with body weight, BMI, neck and waist circumferences, waist to height ratio (WhtR), insulin and HOMA Index, fat mass and visceral fat, and steatosis grade. After 3 months, the liver size showed improvement with positive correlations to all previous variables. Hepatic stiffness (Kpa) positively correlated with neck circumference, visceral fat, and ALT, with basal insulin, gamma-GT, and AST, and with waist circumference, WhtR, and fat mass. The degree of steatosis was positively correlated with more variables and with greater statistical significance at T1 with respect to T0. Particularly, the positive correlations between the degree of steatosis and neck circumference (p < 0.001), HOMA Index, and triglycerides (p < 0.001) appeared to be very significant. NAFLD management in women with metabolic syndrome should be focused on lifestyle modifications. Moreover, liver involvement and improvement at follow-up could be evaluated in a non-invasive manner through ultrasonographic and elastosonographic techniques. Full article

(1) Background: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and the limitations of liver biopsies, multiple non-invasive tests (NITs) have been developed to identify non-alcoholic fatty liver disease (NAFLD) patients at-risk of progression. The availability of these new NITs varies from country to country, and little is known about their implementation and adoption in routine clinical practice. This study aims to explore barriers and facilitators that influence the adoption of NAFLD NITs, from healthcare professionals’ perspectives. (2) Methods: A cross-sectional study was performed using an exploratory mixed-methods approach. Twenty-seven clinicians from eight different countries with different specialties filled in our questionnaire. Of those, 16 participated in semi-structured interviews. Qualitative and quantitative data were collected and summarized using the recently published Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework for new medical technologies in healthcare organizations. (3) Results: Several factors were reported as influencing the uptake of NITs for NAFLD in clinical practice. Among those: insufficient awareness of tests; lack of practical guidelines and evidence for the performance of tests in appropriate patient populations and care settings; and absence of sufficient reimbursement systems were reported as the most important barriers. Other factors, most notably ‘local champions’, proper functional payment systems, and sufficient resources in academic hospitals, were indicated as important facilitating factors. (4) Conclusions: Clinicians see the adoption of NITs for NAFLD as a complex process that is modulated by several factors, such as robust evidence, practical guidelines, a proper payment system, and local champions. Future research could explore perspectives from other stakeholders on the adoption of NITs. Full article

Insulin resistance (IR) is a major contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index has recently gained popularity for the assessment of IR and NAFLD due to its ease of acquisition and calculation. Therefore, we conducted this systematic review and meta-analysis to summarize the existing studies in the literature and provide a quantitative assessment of the significance of the TyG index in predicting the incidence of NAFLD. A comprehensive literature search in PubMed, EMBASE, and Web of Science databases from inception until 25 March 2022 was conducted. Published observational studies that evaluated the association between TyG index and NAFLD among the adult population and reported the hazard ratio (HR) or odds ratio (OR) for this association after multivariate analysis were included. The random-effects model was used as the primary statistical analysis model in the estimation of pooled ORs and HRs with the corresponding confidence intervals (CIs). A total of 17 observational studies, including 121,975 participants, were included. For studies analyzing the TyG index as a categorical variable, both pooled OR (6.00, CI 4.12–8.74) and HR (1.70, CI 1.28–2.27) were significant for the association between TyG index and incident NAFLD. For studies analyzing the TyG index as a continuous variable, pooled OR (2.25, CI 1.66–3.04) showed similar results. Consistent results were obtained in subgroup analyses according to the study design, sample size, ethnicity, and diabetic status. In conclusion, our meta-analysis demonstrates that a higher TyG index is associated with higher odds of NAFLD. TyG index may serve as an independent predictive tool to screen patients at high risk of NAFLD in clinical practice, especially in primary care settings. Patients with a high TyG index should be referred for a liver ultrasound and start intense lifestyle modifications. However, further large-scale prospective cohort studies are necessary to validate our findings. Full article

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI < 60); and (3) control (FLI < 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases. Full article

Background: Structured exercise as part of lifestyle modification plays an important role in the improvement of non-alcoholic fatty liver disease (NAFLD); however, its effectiveness has been shown to vary. This systematic review with meta-analysis investigated the effects of exercise on liver function and insulin resistance markers in patients with NAFLD. Methods: Six electronic databases were searched using terms related to exercise and NAFLD up to March 2022. Data were analyzed using a random-effects model to estimate the standardized mean difference (SMD) and 95% confidence interval. Results: The systematic search identified 2583 articles, of which a total of 26 studies met the inclusion criteria and were eligible. Exercise training had a moderate effect on reducing ALT (SMD: −0.59, p = 0.01) and small effects on reducing AST (SMD: −0.40, p = 0.01) and insulin (SMD: −0.43, p = 0.02). Significant reductions in ALT were found following aerobic training (SMD: −0.63, p < 0.01) and resistance training (SMD: −0.45, p < 0.001). Moreover, reductions in AST were found following resistance training (SMD: −0.54, p = 0.001), but not after aerobic training and combined training. However, reductions in insulin were found following aerobic training (SMD: −0.55, p = 0.03). Exercise interventions for <12 weeks compared to ≥12 weeks were more effective in reducing FBG and HOMA-IR, while interventions for ≥12 weeks compared to <12 weeks were more effective in reducing ALT and AST levels. Conclusions: Our findings support the effectiveness of exercise in improving liver function markers but not in blood glucose control in NAFLD patients. Additional studies are needed to determine the exercise prescription to maximize health in these patients. Full article

Because of their condition, patients with morbid obesity develop several histopathological changes in the liver, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver disease (ESLD). Hence, a liver transplant (LT) becomes an opportune solution for them. Due to many challenges during the perioperative and postoperative periods, these patients are recommended to lose weight before the surgery. There are many proposals to achieve this goal, such as intragastric balloons and many different bariatric surgery (BS) procedures in combination with a preparation diet (very-low-calorie diet, ketogenic diet, etc.). All the interventions focus on losing weight and keeping the continuity and functionality of the digestive tract to avoid postoperative complications. Thus, this review analyzes recent publications regarding the metabolic and pathophysiological impacts of BS in LT patients suffering from NAFLD-related cirrhosis, the effect of weight loss on postoperative complications, and exposes the cost-effectiveness of performing BS before, after, and at liver transplantation. Finally, the authors recommend BS before the LT since there are many positive effects and better outcomes for patients who lose weight before the procedure. Nevertheless, further multicentric studies are needed to determine the generalizability of these recommendations due to their impact on public health. Full article

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD–IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches. Full article