Vanek's Tumour as a Rare Cause of Dyspeptic Syndrome in a Patient with Primary Biliary Cholangitis: A Case Report.

BACKGROUND: Inflammatory Fibroid Polyp (IFP), also known as Vanek's tumour, is a rare mesenchymal gastrointestinal tumour, potentially causing a wide range of clinical manifestations (even though it can be completely asymptomatic) primarily related to the location of the formation. The available evidence suggests a fundamentally non-neoplastic behaviour of IFP. CASE PRESENTATION: A 67-year-old female was presented with persistent dyspepsia despite symptomatic therapy. The patient's medical history included primary biliary cholangitis, managed with ursodeoxycholic acid, non-haemorrhagic uterine fibroids, and right knee arthrosis. Clinical examination revealed mild epigastric tenderness, and esophagogastroduodenoscopy identified a sessile mucosal formation. Histological analysis of biopsy samples revealed a gastric hyperplastic polyp, leading to a subsequent esophagogastroduodenoscopy for polypectomy. The excised specimen confirmed the diagnosis of gastric IFP. Post-polypectomy, the patient experienced progressive symptom amelioration, leading to complete resolution within three weeks. DISCUSSION: This case thus describes a rare cause of dyspeptic syndrome associated with the presence of a gastric IFP, promptly managed and resolved after endoscopic removal of the polyp, with no histological signs of neoplasia within the en bloc resected sample. CONCLUSION: IFP is a possible and rare cause of dyspeptic syndrome. There remain significant challenges in diagnosing this rare condition, which lacks pathognomonic or specific signs and symptoms of its presence (especially when it causes symptoms). Endoscopy, when feasible, remains a cornerstone in the resective management of such lesions.

The influence of acute lifestyle changes on NAFLD evolution in a multicentre cohort: a matter of body composition.

BACKGROUND: Unhealthy lifestyles represent a key element fueling Non-alcoholic fatty liver disease (NAFLD) onset and worsening. We aimed to evaluate the effects of forced acute lifestyle changes on NAFLD evolution. METHODS: 187 NAFLD patients were followed two years pre- and two years during the lockdown social restrictions in three Italian medical centers. For each patient, biochemical, clinical, non-invasive liver fibrosis, nutritional, and body composition data were collected. RESULTS: An increase in fats and carbohydrate intake associated with impaired weekly physical activity during the lockdown was demonstrated as well as an increase in body mass index and waist-hip-ratio (p < 0.0001 for all). Total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, insulin, homeostatic model assessment for insulin resistance, and transaminases worsened during the lockdown (glucose: p = 0.0007; p < 0.0001 for the others). Moreover, NAFLD fibrosis score, liver stiffness, and controlled attenuation parameter were also impaired during the same period (p < 0.0001 for all). The bioelectrical impedance analysis (BIA) evidenced an increase of fat mass (FM), and a reduction of free fat mass (FFM) and body cell mass (BCM) (p < 0.0001 for all). The lockdown overall hepatocellular carcinoma (HCC) and Milan-out HCC occurrence revealed Hazard Ratio (HR): 2.398, 95% Confidence Interval (CI):1.16-5, p = 0.02, and HR:5.931, CI:2-17.6, p = 0.008 respectively. A liver disease stage and comorbidities independent association between both the assessed outcomes and body composition analysis in terms of mean values and variation (T1-T2 Δ) was demonstrated. CONCLUSIONS: The acute lifestyle changes impacted NAFLD evolution via body composition modifications negatively influencing the HCC occurrence.

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review.

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8+ T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.

Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity: The "BE-FIT-IBD" study.

BACKGROUND: The place regular physical activity (PA) should occupy in managing patients with inflammatory bowel diseases (IBD) is unclear. AIM: To assess PA levels and barriers in a southern Italian IBD population. METHODS: IBD patients with non-severe disease activity [assessed with partial Mayo score for ulcerative colitis (UC) and Harvey-Bradshaw index for Crohn's disease] were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire (IPAQ) and to assess disease activity as patient-reported outcomes 2 (PRO-2) and finally to assess habits, beliefs and barriers in conducting regular PA. Clinical, anthropometric and demographic data of patients were also collected. PA was expressed as continuous units of resting metabolic rate (Met) in min/wk. Three PA groups were identified: Inactive (< 700 Met min/wk), sufficiently active (700-2500 Met min/wk) and health enhancing PA (HEPA) (i.e., HEPA active, > 2500 Met min/wk) patients. RESULTS: Included patients (219) showed overall PA levels of 834.5 Met min/wk, with a large proportion (94, 42.9%) classified as inactive while only a minority (9, 4.1%) as health-enhancing PA. Patients without dyslipidaemia (P < 0.0001) or on biologics therapy (P = 0.022) showed better IPAQ scores in moderate activities. UC PRO-2 correlated negatively with IPAQ intense activities scores (τ = -0.156, P = 0.038). PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity (AUC < 0.6). IBD activity did not differ between active and inactive patients (P > 0.05). Active patients expressed the need to discuss PA with their gastroenterologist. Some barriers (e.g., diagnosis of IBD and fear of flare-ups after PA) are significantly more reported by inactive patients. CONCLUSION: A significant rate of physical inactivity was recorded in this setting. IPAQ showed good feasibility. PA should be an element of discussion in IBD visits assessed quickly with non-invasive questionnaires.

Environmental bisphenol A exposure triggers trained immunity-related pathways in monocytes.

Introduction: Trained Immunity represents a novel revolutionary concept of the immunological response involving innate immune cells. Bisphenol A is a well-known endocrine disrupter, widely disseminated worldwide and accumulated in the human body. Due to the increased interest regarding the effects of plastic-derived compounds on the immune system, our purpose was to explore whether BPA was able to induce trained immunity in human primary monocytes in vitro using low environmental concentrations. Materials and methods: We extracted BPA from the serum of 10 healthy individuals through a liquid-liquid extraction followed by a solid phase extraction and measured the concentration using an HPLC system coupled to a triple quadrupole mass spectrometer. In parallel, monocytes were isolated from whole blood and acutely stimulated or trained with BPA at three different concentrations (1 nM, 10 nM, 20 nM). Pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-10) production were assessed after 24 hours of acute stimulation and after Lipopolysaccharide (LPS) rechallenge. A comprehensive overview of the metabolic changes after BPA acute stimulation and trained immunity induction was assessed through extracellular lactate measurements, Seahorse XFb metabolic flux analysis and ROS production. Results: Monocytes primed with BPA showed increased pro- and anti-inflammatory cytokine responses upon restimulation, sustained by the modulation of the immunometabolic circuits. Moreover, we proved the non-toxic effect of BPA at each experimental concentration by performing an MTT assay. Additionally, correlation analysis were performed between pro- and anti-inflammatory cytokines production after LPS acute stimulation or BPA-mediated trained immunity and BPA serum concentrations showing a significant association between TNF-α and BPA circulating levels. Discussion: Overall, this study pointed out for the first time the immunological effects of an environmental chemical and plastic-derived compound in the induction of trained immunity in a healthy cohort.

Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.

Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as "small ncRNAs" (sncRNAs) and "long ncRNAs" (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression.

The use of bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water improves functional gastrointestinal symptoms in patients with non-alcoholic fatty liver disease: A prospective study.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease is increasingly gaining epidemiological ground in liver diseases. Among the proposed non-pharmacologic interventions, dietary interventions have been widely used. Several patients suffering from it complain of gastrointestinal symptoms unrelated to organic gastrointestinal tract disease. However, the role of drinking water quality modifications in this regard has not been investigated in depth. METHODS: Patients with upper or lower functional gastrointestinal symptoms were enrolled and divided into groups based on bright liver ultrasound relief's presence (SP) or absence (NSP). These patients were asked to drink bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water (Fonte Essenziale ®) for six months. Participants were assessed at baseline (T0), at the end of six months of drinking water intake (T6), and after an additional six months of washout (T12) by questionnaires designed to evaluate lower and upper gastrointestinal symptoms (Leeds dyspepsia score, short form) severity and frequency. RESULTS: A total of 61 patients were enrolled. In the SP population, the severity of lower gastrointestinal symptoms improved between T0-T6 (Z: -2.437; ES: 0.312) and worsened after the water washout (Z: -2.492; ES: 0.319). The same was for the Leeds score severity sub score in T0-T6 (Z: -2.850; ES: 0.364) and T6-T12 (Z: -2.921; ES: 0.374). These improvements seem unrelated to the severity of liver steatosis at baseline. Furthermore, no safety issues were recorded while taking the water nor during the six-month follow-up afterwards. CONCLUSION: Regular six-month intake of 400 mL of Fonte Essenziale® water was associated, in the absence of dietary regimen modifications, with an improvement in some qualitative and quantitative features of upper and lower functional gastrointestinal symptoms in both an SP and NSP sample.

Quality of bowel preparation in patients with inflammatory bowel disease undergoing colonoscopy: What factors to consider?

An adequate bowel preparation in patients with inflammatory bowel disease (IBD) is a prerequisite for successful colonoscopy for screening, diagnosis, and surveillance. Several bowel preparation formulations are available, both high- and low-volume based on polyethylene glycol. Generally, low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate, oral sulphate solution, and oral sodium phosphate-based solutions. Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required, with current evidence from existing studies being inconclusive. New frontiers are also moving towards the use of alternatives to anterograde ones, using preparations based on retrograde colonic lavage.

The urotensin-II receptor: A marker for staging and steroid outcome prediction in ulcerative colitis.

BACKGROUND: Urotensin-II receptor- (UTR) related pathway exerts a key-role in promoting inflammation. The aim was to assess the relationship between UTR expression and clinical, endoscopic and biochemical severity of ulcerative colitis (UC), exploring its predictivity of intravenous (iv) steroid administration therapeutic outcome. METHODS: One-hundred patients with first diagnosis of UC and 44 healthy subjects were enrolled. UTR expression was assessed by qPCR, Western Blot (WB) and immunohistochemistry (IHC). Clinical, endoscopic and histological activity of UC were evaluated by using Truelove and Witts (T&W) severity index, Mayo Endoscopic Score (MES), and Truelove and Richards Index (TRI). The partial and full Mayo scores (PMS and FMS) were assessed to stage the disease. RESULTS: The UTR expression, resulted higher in the lesioned mucosa of UC patients in comparison to healthy subjects (p < .0001 all). Direct relationship between UTR (mRNA and protein) expression and disease severity assessment (T&W, PMS, MES and TRI) was highlighted (p < .0001 all). UTR expression resulted also higher in the 72 patients requiring iv steroids administration compared to those who underwent alternative medications, (p < .0001). The 32 steroid-non-responders showed an increased UTR expression (WB, IHC and qPCR from lesioned mucosa), compared to 40 steroid-responders (p: .0002, .0001, p < .0001 respectively). The predictive role of UTR expression (p < .05) on the negative iv steroids administration therapeutic outcome was highlighted and ROC curves identified the thresholds expressing the better predictive performance. CONCLUSIONS: UTR represents a promising inflammatory marker related to clinical, endoscopic, and histological disease activity as well as a predictive marker of steroid administration therapeutic outcome in the UC context.

A 60-Year-Old Woman with Primary Biliary Cholangitis and Crohn's Ileitis Following the Suspension of Ursodeoxycholic Acid.

BACKGROUND There is a recognized association between inflammatory bowel disease (IBD) and hepatobiliary autoimmune disease, particularly primary sclerosing cholangitis (PSC). There have been fewer reported cases of IBD and primary biliary cholangitis (PBC), which is treated with ursodeoxycholic acid (UDCA). This report presents the case of a 60-year-old woman with PBC who was diagnosed with Crohn's ileitis after suspension of UDCA treatment. CASE REPORT A 66-year-old female patient with PBC was admitted to our department for irrepressible chronic diarrhea and recurrent abdominal pain. PBC was diagnosed on the basis of serological data: chronic (>6 months) increase in alkaline phosphatase (ALP) associated with positivity for specific anti-nuclear antibodies (sp100 and gp210), without requiring a liver biopsy and a magnetic resonance cholangiopancreatography to rule out PSC. Given the intolerance and non-responsiveness according to the Toronto criteria (ALP <1.67 times the normal limit after 2 years) to UDCA at 15 mg/kg/day, an oral monotherapy treatment using obeticholic acid at 5 mg/day was prescribed. The patient complained of abdominal pain and upper gastrointestinal symptoms. The endoscopic/histologic and radiologic examinations supported the diagnosis of Crohn's ileitis. Given the potential benefits to PBC patients of what is described as off-label therapy, budesonide at a dosage of 9 mg/day p.o. was also administered. One month after discharge, an improvement was observed both in the cholestasis indices and in gastrointestinal symptoms. CONCLUSIONS This report presents a case of PBC in which the patient was diagnosed with Crohn's ileitis after cessation of treatment with UDCA, and highlights the importance of recognizing the association between autoimmune hepatobiliary disease and IBD.

Just Drink a Glass of Water? Effects of Bicarbonate-Sulfate-Calcium-Magnesium Water on the Gut-Liver Axis.

Background and Aim: Fonte Essenziale® water is a bicarbonate-sulfate-calcium-magnesium water, low in sodium, recognized by the Italian health care system in hydropinotherapy and hepatobiliary dyspepsia therapy. We wanted to explore its effects on the gut-liver axis and microbiota in non-alcoholic fatty liver disease patients. Patients and Methods: We considered enrollment for 70 patients, of which four were excluded. We finally enrolled 55 patients with ultrasound-documented steatosis (SPs+) and 11 patients without it (SPs-). They then drank 400 ml of water for 6 months in the morning on an empty stomach. Routine hematochemical and metabolic parameters, oxidative stress parameters, gastrointestinal hormone levels, and fecal parameters of the gut microbiota were evaluated at three different assessment times, at baseline (T0), after 6 months (T6), and after a further 6 months of water washout (T12). We lost, in follow-up, 4 (T6) and 22 (T12) patients. Results: Between T0-T6, we observed a significant Futuin A and Selenoprotein A decrease and a GLP-1 and PYY increase in SPs+ and the same for Futuin A and GLP-1 in SPs-. Effects were lost at T12. In SPs+, between T0-T12 and T6-12, a significant reduction in Blautia was observed; between T0-T12, a reduction of Collinsella unc. was observed; and between T0-T12 and T6-12, an increase in Subdoligranulum and Dorea was observed. None of the bacterial strains we analyzed varied significantly in the SPs- population. Conclusion: These results indicate beneficial effects of water on gastrointestinal hormones and hence on the gut-liver axis in the period in which subjects drank water both in SPs- and in SPs+.

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications.

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.

The Lesson from the First Italian Lockdown: Impacts on Anxiety and Depressive Symptoms and Sleep Quality in Patients with Remission of Inflammatory Bowel Disease.

BACKGROUND: During the COVID-19 pandemic in Italy, decisions were taken to adopt restrictive legislative measures, such as the first half of the 2020 lockdown. In those months, patients with inflammatory bowel disease experienced social isolation and reduced access to health care. OBJECTIVE: We aimed to evaluate, in this condition, the presence of remission subgroups that were most impacted by the lockdown. METHODS: During the first Italian lockdown, we recruited patients with remission of inflammatory bowel disease by administering an online questionnaire including patient demographics, the Beck Anxiety Questionnaire Inventory, the Beck Depression Inventory questionnaire, and the Pittsburg Sleep Quality Index, all validated standardized questionnaires for anxiety symptom levels, depression, and sleep quality. RESULTS: Our results showed how female patients (p<0.0001) with Crohn's disease (p<0.001) experienced worse levels of anxiety symptoms. Female patients (p<0.0001) between 50 and 60 years of age (p=0.013) with Crohn's disease (p=0.047) experienced worse levels of depressive symptoms. Females also experienced significantly worse sleep levels (p<0.001). We found a correlation between the number of sleeping hours (p<0.001) and the time taken to fall asleep (p<0.001) and the Beck Anxiety Questionnaire Inventory,which showed a linear worsening of the number of minutes it took to fall asleep, and the Beck Depression Inventory questionnaire. CONCLUSION: Among patients with remission of inflammatory bowel disease, female patients, patients with Crohn's disease, and people aged between 50 and 70 years should be considered for screening for anxiety and depression disorders and an assessment of sleep quality.

PNPLA3, TM6SF2, and MBOAT7 Influence on Nutraceutical Therapy Response for Non-alcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Introduction: PNPLA3, TM6SF2, and MBOAT7 genes play a crucial role in non-alcoholic fatty liver disease (NAFLD) development and worsening. However, few data are available on their treatment response influence. The aim of this trial is to explore the effect derived from silybin-phospholipids complex (303 mg of silybin-phospholipids complex, 10 µg of vitamin D, and 15 mg of vitamin E twice a day for 6 months) oral administration in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926, or MBOAT7-rs641738 genetic variants. Materials and Methods: In all, 92 biopsy-proven NAFLD patients were grouped in 30 NAFLD wild type controls, 30 wild type treated patients, and 32 mutated treated ones. We assessed glycemia (FPG), insulinemia, HOMA-IR, aspartate and alanine aminotransferases (AST, ALT), C-reactive protein (CRP), thiobarbituric acid reactive substance (TBARS), stiffness, controlled attenuation parameter (CAP), dietary daily intake, and physical activity at baseline and end of treatment. Results: The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS (p < 0.05), whereas no improvements were recorded in the other two study groups. NAFLD wild type treated patients showed higher possibilities of useful therapeutic outcome (p < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group. Discussion: The assessed mutations are independently associated with no response to a silybin-based therapeutic regimen and could be considered as useful predictive markers in this context. Clinical Trial Registry Number: www.ClinicalTrials.gov, identifier: NCT04640324.

Nutrigenomics and Nutrigenetics in Metabolic- (Dysfunction) Associated Fatty Liver Disease: Novel Insights and Future Perspectives.

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition's capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients' clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context.

The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights.

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression.

Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: The Contribution of Oxidative Stress in the Disease Progression.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis with a potential development of hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and fibrosis. Several studies reported that insulin resistance, redox unbalance, inflammation, and lipid metabolism dysregulation are involved in NAFLD progression. However, the mechanisms beyond the evolution of simple steatosis to NASH are not clearly understood yet. Recent findings suggest that different oxidized products, such as lipids, cholesterol, aldehydes and other macromolecules could drive the inflammation onset. On the other hand, new evidence indicates innate and adaptive immunity activation as the driving force in establishing liver inflammation and fibrosis. In this review, we discuss how immunity, triggered by oxidative products and promoting in turn oxidative stress in a vicious cycle, fuels NAFLD progression. Furthermore, we explored the emerging importance of immune cell metabolism in determining inflammation, describing the potential application of trained immune discoveries in the NASH pathological context.

The Bisphenol A Induced Oxidative Stress in Non-Alcoholic Fatty Liver Disease Male Patients: A Clinical Strategy to Antagonize the Progression of the Disease.

:Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 g of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. METHODS: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. RESULTS: A direct proportionality between TBARS levels and BPA exposure was shown (p < 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p < 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p < 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). CONCLUSIONS: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

Chemical Effect of Bisphenol A on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is considered a predominant chronic liver disease worldwide and a component of metabolic syndrome. Due to its relationship with multiple organs, it is extremely complex to precisely define its pathogenesis as well as to set appropriate therapeutic and preventive strategies. Endocrine disruptors (EDCs) in general, and bisphenol A (BPA) in particular, are a heterogeneous group of substances, largely distributed in daily use items, able to interfere with the normal signaling of several hormones that seem to be related to type 2 diabetes mellitus (T2DM), obesity, and other metabolic disorders. It is reasonable to hypothesize a BPA involvement in the pathogenesis and evolution of NAFLD. However, its mechanisms of action as well as its burden in the vicious circle that connects obesity, T2DM, metabolic syndrome, and NAFLD still remain to be completely defined. In this review we analyzed the scientific evidence on this promising research area, in order to provide an overview of the harmful effects linked to the exposure to EDCs as well as to frame the role that BPA would have in all phases of NAFLD evolution.

Surgical treatment of congenital rhabdoid tumor in a 10-day-old newborn.

BACKGROUND: Malignant rhabdoid tumors are rare and aggressive tumors of pediatric age. The primary tumor can occur in different localizations, but it mainly involves kidney, soft tissue, or central nervous system. It has been associated to a poor diagnosis. METHODS: The authors present the case of a 10-day-old newborn affected by a bulky nasofronto-orbitary neoplasm. The patient underwent radical surgical treatment and further excision of a preauricular metastasis combined with postoperative chemotherapy treatment. RESULTS: The authors adopted a diagnostic and therapeutic protocol according to international guidelines, not without difficulty because the first histological report showed esthesioneuroblastoma. The rarity and aggresivity of rhabdoid tumor and the precocity of onset in our patient presented a difficulty to define prognostic factors and survival rates, as well as therapeutic plan of treatment. CONCLUSIONS: The authors underline the importance of a correct prenatal diagnosis and an early surgical treatment to reach the complete healing of the patient.