Publications by authors named "Marcello Dallio"

62 Publications

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

Front Med (Lausanne) 2021 8;8:734847. Epub 2021 Oct 8.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

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. 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. The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS ( < 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 ( < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group. 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. www.ClinicalTrials.gov, identifier: NCT04640324.
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http://dx.doi.org/10.3389/fmed.2021.734847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531439PMC
October 2021

How Immunotherapy Has Changed the Continuum of Care in Hepatocellular Carcinoma.

Cancers (Basel) 2021 Sep 21;13(18). Epub 2021 Sep 21.

Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania "L. Vanvitelli", 80100 Naples, Italy.

Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide. The use of local treatment, such as surgical resection, liver transplant, and local ablation, has improved the survival of patients with HCC detected at an early stage. Until recently, the treatment of patients with metastatic disease was limited to the use of the multikinase inhibitor (MKI) sorafenib with a marginal effect on survival outcome. New target approaches, such as the oral MKI lenvatinib in first-line treatment and regorafenib, ramucirumab, and cabozantinib in later lines of therapy, have demonstrated efficacy in patients with preserved liver function (Child-Pugh class A) and good performance status. On the other hand, the implementation of immune checkpoint inhibitors directed against PD-1 (nivolumab and pembrolizumab), PD-L1 (atezolizumab), and anti-CTLA4 (ipilimumab) in the management of advanced HCC has strongly changed the continuum of care of HCC. Future research should include the evaluation of molecular biomarkers that can help patient selection and provide new insight on potential combined approaches. In this review, we provide an overview of the clinical evidence of the use of immune checkpoint inhibitors in HCC, and discuss how immunotherapy has been implemented into the continuum of HCC care.
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http://dx.doi.org/10.3390/cancers13184719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466991PMC
September 2021

Corrigendum to "Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease".

Oxid Med Cell Longev 2021 28;2021:9757921. Epub 2021 Jul 28.

Internal Medicine and Hepatology Division, Department of Medicine, University of Medicine of Salerno, Salerno, Italy.

[This corrects the article DOI: 10.1155/2018/9547613.].
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http://dx.doi.org/10.1155/2021/9757921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349283PMC
July 2021

Risk Factors for Liver Decompensation and HCC in HCV-Cirrhotic Patients after DAAs: A Multicenter Prospective Study.

Cancers (Basel) 2021 Jul 29;13(15). Epub 2021 Jul 29.

Department of Tropical and Infectious Disease, Policlinico Umberto I, 00161 Rome, Italy.

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking.

Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis.

Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events ( < 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0; 95% CI 1.1-14.1) and genotype different from 1 (HR 7.5; 95% CI 2.1-27.3) were both independent predictors of liver decompensation. Baseline LSM > 20 KPa (HR 7.2; 95% CI 1.9-26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events.

Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR.
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http://dx.doi.org/10.3390/cancers13153810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345116PMC
July 2021

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

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

Nutrients 2021 May 15;13(5). Epub 2021 May 15.

Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy.

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.
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http://dx.doi.org/10.3390/nu13051679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156164PMC
May 2021

The analysis of alcohol consumption during the severe acute respiratory syndrome coronavirus 2 Italian lockdown.

Minerva Med 2021 May 5. Epub 2021 May 5.

Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.

Background: The SARS-CoV-2 lockdown resulted in deep changes of lifestyles, promoting in many people the onset of psychological symptoms generally associated with drug and alcohol abuse. The aim was to assess the variation of alcohol drinking habits in a sample of Italian citizens during lockdown and to identify the psychosocial factors surrounding it.

Methods: An online anonymous questionnaire was created and submitted from 9th April 2020 to 28th April 2020. Questions were related to personal psychosocial details and alcohol drinking habits during the lockdown, including Alcohol Use Disorders Identification Test (AUDIT C) questions.

Results: On a total of 1234 surveys the increase of both anxiety and fear was largely detected (63% and 61% respectively). The 18% increased alcohol consumption during the lockdown and it showed a significant correlation with anxiety and fear experienced (both p<0.001). The relative risk for 7 to 9 and more than 10 drinks per day consumption were directly linked to these symptoms (p<0.001). The most involved categories of participants showed this harmful association were self-employed workers and participants who live alone, subject aged 30-50 with high level of instruction or students and not occupied people in the age range 18-19 (all p<0.001). Additionally, the subset of the study population that showed low alcohol consumption before the lockdown has demonstrated the worsening of alcohol assumption during the quarantine (p<0.0001).

Conclusions: Several psychosocial factors are involved in determining the increase of alcohol consumption during lockdown and need the healthcare support to avoid awful impact on human life.
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http://dx.doi.org/10.23736/S0026-4806.21.07354-7DOI Listing
May 2021

Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort.

BMC Infect Dis 2021 May 4;21(1):413. Epub 2021 May 4.

Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

Background: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA.

Methods: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication.

Results: We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0-44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00-6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18-3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08-2.85) and increased INR (HR = 2.41; 95% CI 1.51-3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83).

Conclusions: Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.
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http://dx.doi.org/10.1186/s12879-021-06053-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094561PMC
May 2021

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

Nutrients 2021 Apr 16;13(4). Epub 2021 Apr 16.

Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology, "Scuola Medica Salernitana", University of Salerno, 84084 Salerno, Italy.

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.
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http://dx.doi.org/10.3390/nu13041314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074203PMC
April 2021

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials.

Nutrients 2021 Mar 13;13(3). Epub 2021 Mar 13.

Internal Medicine and Hepatology Division, Department of Medicine and Surgery "Scuola Medica Salernitana", University of Salerno, Baronissi, 84081 Salerno, Italy.

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.
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http://dx.doi.org/10.3390/nu13030933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999728PMC
March 2021

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease.

Nutrients 2021 02 3;13(2). Epub 2021 Feb 3.

Department of Health Sciences, "Magna Graecia" University, Viale Europa, 88100 Catanzaro, Italy.

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.
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http://dx.doi.org/10.3390/nu13020494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913263PMC
February 2021

Untargeted metabolomics as a diagnostic tool in NAFLD: discrimination of steatosis, steatohepatitis and cirrhosis.

Metabolomics 2021 01 16;17(2):12. Epub 2021 Jan 16.

Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy.

Introduction: Non-Alcoholic Fatty Liver Disease encompasses a spectrum of diseases ranging from simple steatosis to steatohepatitis (or NASH), up to cirrhosis and hepatocellular carcinoma (HCC). The challenge is to recognize the more severe and/or progressive pathology. A reliable non-invasive method does not exist. Untargeted metabolomics is a novel method to discover biomarkers and give insights on diseases pathophysiology.

Objectives: We applied metabolomics to understand if simple steatosis, steatohepatitis and cirrhosis in NAFLD patients have peculiar metabolites profiles that can differentiate them among each-others and from controls.

Methods: Metabolomics signatures were obtained from 307 subjects from two separated enrollments. The first collected samples from 69 controls and 144 patients (78 steatosis, 23 NASH, 15 NASH-cirrhosis, 8 HCV-cirrhosis, 20 cryptogenic cirrhosis). The second, used as validation-set, enrolled 44 controls and 50 patients (34 steatosis, 10 NASH and 6 NASH-cirrhosis).The "Partial-Least-Square Discriminant-Analysis"(PLS-DA) was used to reveal class separation in metabolomics profiles between patients and controls and among each class of patients, and to reveal the metabolites contributing to class differentiation.

Results: Several metabolites were selected as relevant, in particular:Glycocholic acid, Taurocholic acid, Phenylalanine, branched-chain amino-acids increased at the increase of the severity of the disease from steatosis to NASH, NASH-cirrhosis, while glutathione decreased (p < 0.001 for each). Moreover, an ensemble machine learning (EML) model was built (comprehending 10 different mathematical models) to verify diagnostic performance, showing an accuracy > 80% in NAFLD clinical stages prediction.

Conclusions: Metabolomics profiles of NAFLD patients could be a useful tool to non-invasively diagnose NAFLD and discriminate among the various stages of the disease, giving insights into its pathophysiology.
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http://dx.doi.org/10.1007/s11306-020-01756-1DOI Listing
January 2021

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

Int J Mol Sci 2021 Jan 4;22(1). Epub 2021 Jan 4.

Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131 Naples, Italy.

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.
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http://dx.doi.org/10.3390/ijms22010436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795122PMC
January 2021

Extra-Gastric Manifestations of Infection.

J Clin Med 2020 Nov 30;9(12). Epub 2020 Nov 30.

Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, via Pansini 5, 80131 Naples, Italy.

() is a Gram-negative flagellated microorganism that has been extensively studied since its first isolation due to its widespread diffusion and association with numerous diseases. While the bacterium is proved to be a causative factor for a number of gastric diseases such as gastritis, gastric adenocarcinoma, and MALT-lymphoma, its role at other gastrointestinal levels and in other systems is being thoroughly studied. In this article, we reviewed the latest published clinical and laboratory studies that investigated associations of with hematologic diseases such as Vitamin B12- and iron-deficiency anemia, primary immune thrombocytopenia, and with a number of dermatologic and ophthalmic diseases. In addition, the putative role of the bacterium in inflammatory bowel diseases, esophageal disorders, metabolic, diseases, neurologic diseases and allergy were outlined.
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http://dx.doi.org/10.3390/jcm9123887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761397PMC
November 2020

Light Alcohol Drinking and the Risk of Cancer Development: A Controversial Relationship.

Rev Recent Clin Trials 2020 ;15(3):164-177

Department of Precision Medicine, University of Campania Luigi Vanvitelli, NA, Italy.

Background: In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12.5g per day) is still unknown.

Objective: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset.

Methods: To collect the scientific evidences regarding this topic the keywords "light alcohol drinking", "light alcohol consumption" and "cancer", were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded.

Results: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed.

Conclusion: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.
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http://dx.doi.org/10.2174/1574887115666200628143015DOI Listing
October 2021

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

Int J Environ Res Public Health 2020 05 12;17(10). Epub 2020 May 12.

Department of Precision Medicine, University of Campania Luigi Vanvitelli, via Pansini 5, 80131 Naples, Italy.

: 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 ( < 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.
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http://dx.doi.org/10.3390/ijerph17103369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277712PMC
May 2020

Critical review on the use and abuse of alcohol. When the dose makes the difference.

Minerva Med 2020 Aug 23;111(4):344-353. Epub 2020 Apr 23.

Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples, Italy.

Nowadays harmful alcohol consumption represents one of the most important risk factors for the development of several type of chronic and acute diseases in the western countries, contributing to a great number of deaths. Focusing the attention on cancer development and progression, the scientific community has a large consensus in declaring the existence of a harmful association between alcohol consumption and liver, breast, upper aerodigestive tract (mouth, oropharynx, hypopharynx, and esophagus), pancreas and colon cancer appearance. However the precise biological links by which the alcohol could be responsible for cancer initiation and progression are not fully understood yet, even if the International Agency for Research on Cancer (IARC) indicated both ethanol and acetaldehyde as carcinogen for humans. The possible explanation of the effect exerted by ethanol and acetaldehyde could be related to direct genotoxicity, hormonal disturbance, triggering of oxidative stress and inflammation. In this review, we examine the relationship between alcohol dosage and associated diseases, with focus on alcohol-related cancers. Furthermore, to understand the potential molecular mechanisms of these diseases, the results of in vivo experiments on animal models were discussed.
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http://dx.doi.org/10.23736/S0026-4806.20.06584-2DOI Listing
August 2020

Non-bismuth and bismuth quadruple therapies based on previous clarithromycin exposure are as effective and safe in an area of high clarithromycin resistance: A real-life study.

Helicobacter 2020 Aug 20;25(4):e12694. Epub 2020 Apr 20.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Background: Bismuth quadruple (BQT) and non-bismuth quadruple (N-BQT) therapies are the recommended first-line treatments for Helicobacter (H.) pylori infection.

Objective: To compare the efficacy of BQT and N-BQT in clinical practice in an area with high clarithromycin resistance, choosing the regimen on the basis of previous exposure to clarithromycin.

Methods: A total of 404 consecutive H pylori-positive, naïve patients were enrolled. A total of 203 patients without previous exposure to clarithromycin received N-BQT, 100 patients for 10 days and 103 for 14 days, whereas 201 with previous exposure to clarithromycin received 10-day BQT. Efficacy and treatment-related adverse events were assessed.

Results And Conclusions: Eradication rates by intention-to-treat analysis were 88.2% for N-BQT and 91.5% for BQT (P = .26); per-protocol analysis eradication rates were 91.2% and 95.8% for N-BQT and BQT, respectively (P = .07). Eradication rates were significantly higher with 14-day than 10-day CT (P < .003). Almost all patients had a good compliance with both N-BQT (95.6%) and BQT (95%). Adverse events occurred in 24.1% and 26.9% (P = .53) of patients in the N-BQT and BQT group, respectively. In conclusion, clarithromycin-containing non-bismuth or bismuth quadruple therapy, based on the knowledge of previous clarithromycin exposure, is effective and safe even in an area of high prevalence of clarithromycin-resistant H pylori strains.
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http://dx.doi.org/10.1111/hel.12694DOI Listing
August 2020

Inflammatory Bowel Diseases: The Role of Gut Microbiota.

Curr Pharm Des 2020 ;26(25):2951-2961

Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ''Luigi Vanvitelli'' and University Hospital, Naples, Italy.

Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.
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http://dx.doi.org/10.2174/1381612826666200420144128DOI Listing
January 2021

Dimethyl fumarate ameliorates hepatic inflammation in alcohol related liver disease.

Liver Int 2020 07 6;40(7):1610-1619. Epub 2020 May 6.

Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria.

Background & Aims: Alcohol-related liver disease (ALD) comprises different liver disorders which impose a health care issue. ALD and particularly alcoholic steatohepatitis, an acute inflammatory condition, cause a substantial morbidity and mortality as effective treatment options remain elusive. Inflammation in ALD is fuelled by macrophages (Kupffer cells [KCs]) which are activated by intestinal pathogen associated molecular patterns, eg lipopolysaccharide (LPS), disseminated beyond a defective intestinal barrier. We hypothesized that the immunomodulator dimethyl-fumarate (DMF), which is approved for the treatment of human inflammatory conditions such as multiple sclerosis or psoriasis, ameliorates the course of experimental ALD.

Methods: Dimethyl-fumarate or vehicle was orally administered to wild-type mice receiving a Lieber-DeCarli diet containing 5% ethanol for 15 days. Liver injury, steatosis and inflammation were evaluated by histology, biochemical- and immunoassays. Moreover, we investigated a direct immunosuppressive effect of DMF on KCs and explored a potential impact on ethanol-induced intestinal barrier disruption.

Results: Dimethyl-fumarate protected against ethanol-induced hepatic injury, steatosis and inflammation in mice. Specifically, we observed reduced hepatic triglyceride and ALT accumulation, reduced hepatic expression of inflammatory cytokines (Tnf-α, Il-1β, Cxcl1) and reduced abundance of neutrophils and macrophages in ethanol-fed and DMF-treated mice when compared to vehicle. DMF protected against ethanol-induced barrier disruption and abrogated systemic LPS concentration. In addition, DMF abolished LPS-induced cytokine responses of KCs.

Conclusions: Dimethyl-fumarate counteracts ethanol-induced barrier dysfunction, suppresses inflammatory responses of KCs and ameliorates hepatic inflammation and steatosis, hallmarks of experimental ALD. Our data indicates that DMF treatment might be beneficial in human ALD and respective clinical trials are eagerly awaited.
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http://dx.doi.org/10.1111/liv.14483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383968PMC
July 2020

Adherence and Effects Derived from FODMAP Diet on Irritable Bowel Syndrome: A Real Life Evaluation of a Large Follow-Up Observation.

Nutrients 2020 Mar 27;12(4). Epub 2020 Mar 27.

Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, via Pansini 5, 80131 Naples, Italy.

Introduction: Irritable bowel syndrome represents one of the most difficult gastroenterological diseases to treat, that usually induces the patients to follow different drug therapies, often not useful in symptom control. In this scenario low FODMAP diet could have positive effects in patients with irritable bowel syndrome, even because this type of diet regimen is characterized by a low gluten amount due to the exclusion of cereals.

Methods: We enrolled 120 patients with irritable bowel syndrome, according to the Rome IV criteria, who were referred to Hepatogastroenterology Division of the University of Campania L. Vanvitelli from June to December 2018. They underwent a low FODMAP diet for six weeks, followed by a gradual weekly reintroduction of every category of food for three months. The patients had a follow-up evaluation for six months after the end of food reintroduction period. We measured abdominal pain with subjective numerical scale from 0 to 10. We evaluated other gastrointestinal symptoms with a questionnaire about symptoms of lower digestive tract, evaluating their frequency and intensity. We also evaluated the impact of irritable bowel syndrome on daily life with neurological bowel dysfunction score.

Results: We obtained a good patient-adherence to diet and a statistically significant decrease of abdominal pain, bloating, flatulence, diarrhea, constipation, and neurological bowel dysfunction score ( < 0.001) at the end of the diet. These results remained constant in the follow-up period.

Conclusions: We recommend the use of a low FODMAP diet regimen in patients with irritable bowel syndrome in order to control the symptoms and improve the quality of life.
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http://dx.doi.org/10.3390/nu12040928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231245PMC
March 2020

Alcohol associated liver disease 2020: A clinical practice guideline by the Italian Association for the Study of the Liver (AISF).

Dig Liver Dis 2020 04 27;52(4):374-391. Epub 2020 Jan 27.

National Institute of Gastroenterology "S. De Bellis" Research Hospital, Castellana Grotte, Italy.

Alcohol use disorder which includes alcohol abuse and dependence represents one of the leading risk factors for premature mortality in Europe and it is responsible of over 200 conditions, including neuropsychiatric disorders, chronic diseases, cancers and accidents leading to permanent disability. Alcohol use disorder represents the most common cause of liver damage in the Western world, with a wide spectrum of diseases ranging from steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. The present clinical practice guidelines by the Italian Association for the Study of the Liver (AISF) are focused on the current knowledge about epidemiology, pathophysiology, clinical features, diagnosis and treatment of alcohol associated liver disease, aiming to provide practical recommendations on the management of this complex pathological condition.
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http://dx.doi.org/10.1016/j.dld.2019.12.008DOI Listing
April 2020

Cirrhosis and frailty assessment in elderly patients: A paradoxical result.

Medicine (Baltimore) 2020 Jan;99(2):e18501

Department of Advanced Medical and Surgical Sciences - University of Campania Luigi Vanvitelli Naples, Italy.

The frailty represents a key determinant of elderly clinical assessment, especially because it allows the identification of risk factors potentially modifiable by clinical and therapeutic interventions. The frailty assessment in elderly patients usually is made by using of Fried criteria. However, to assess the frailty in cirrhotic patients, multiple but different tools are used by researchers. Thus, we aimed to compare frailty prevalence in elderly patients with well-compensated liver cirrhosis and without cirrhosis, according to Fried criteria.Among 205 elderly patients screened, a total of 148 patients were enrolled. The patients were divided into 2 groups according to the presence/absence of well-compensated liver cirrhosis.After clinical examination with conventional scores of cirrhosis, all patients underwent anthropometric measurements, nutritional, biochemical, comorbidity, and cognitive performances. Frailty assessment was evaluated according to Fried frailty criteria.Unexpectedly, according to the Fried criteria, non-cirrhotic patients were frailer (14.2%) than well-compensated liver cirrhotic patients (7.5%). The most represented Fried criterion was the unintentional weight loss in non-cirrhotic patients (10.1%) compared to well-compensated liver cirrhotic patients (1.4%). Moreover, cumulative illness rating scale -G severity score was significantly and positively associated with frailty status (r = 0.234, P < .004). In a multivariate linear regression model, only female gender, body mass index and mini nutritional assessment resulted associated with frailty status, independently of other confounding variables.Despite the fact that elderly cirrhotic patients are considered to be frailer than the non-cirrhotic elderly patient, relying solely on "mere visual appearance," our data show that paradoxically non-cirrhotic elderly patients are frailer than elderly well-compensated liver cirrhotic patients. Thus, clinical implication of this finding is that frailty assessment performed in the well-compensated liver cirrhotic patient can identify those cirrhotic patients who may benefit from tailored interventions similarly to non-cirrhotic elderly patients.
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http://dx.doi.org/10.1097/MD.0000000000018501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959886PMC
January 2020

Evaluation of the Effect Derived from Silybin with Vitamin D and Vitamin E Administration on Clinical, Metabolic, Endothelial Dysfunction, Oxidative Stress Parameters, and Serological Worsening Markers in Nonalcoholic Fatty Liver Disease Patients.

Oxid Med Cell Longev 2019 15;2019:8742075. Epub 2019 Oct 15.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138 Naples, Italy.

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor , transforming growth factor , interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline ( < 0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients ( < 0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome ( < 0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.
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http://dx.doi.org/10.1155/2019/8742075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815609PMC
May 2020

Pharmacological Therapy of Non-Alcoholic Fatty Liver Disease: What Drugs Are Available Now and Future Perspectives.

Int J Environ Res Public Health 2019 11 7;16(22). Epub 2019 Nov 7.

Section of Gastroenterology and Hepatology, PROMISE, Policlinico Universitario Paolo Giaccone, Piazza delle Cliniche 2, 90127 Palermo, Italy.

The non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease as well as the first cause of liver transplantation. NAFLD is commonly associated with metabolic syndrome (MetS), and this is the most important reason why it is extremely difficult to treat this disease bearing in mind the enormous amount of interrelationships between the liver and other systems in maintaining the metabolic health. The treatment of NAFLD is a key point to prevent NASH progression to advanced fibrosis, to prevent cirrhosis and to prevent the development of its hepatic complications (such as liver decompensation and HCC) and even extrahepatic one. A part of the well-known healthy effect of diet and physical exercise in this setting it is important to design the correct pharmaceutical strategy in order to antagonize the progression of the disease. In this regard, the current review has the scope to give a panoramic view on the possible pharmacological treatment strategy in NAFLD patients.
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http://dx.doi.org/10.3390/ijerph16224334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888162PMC
November 2019

NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome.

Int J Environ Res Public Health 2019 09 14;16(18). Epub 2019 Sep 14.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.
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http://dx.doi.org/10.3390/ijerph16183415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765902PMC
September 2019

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

Int J Environ Res Public Health 2019 08 28;16(17). Epub 2019 Aug 28.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", via Pansini 5, 80131 Naples, Italy.

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.
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http://dx.doi.org/10.3390/ijerph16173134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747307PMC
August 2019

Diet and Non-Alcoholic Fatty Liver Disease: The Mediterranean Way.

Int J Environ Res Public Health 2019 08 21;16(17). Epub 2019 Aug 21.

Department of Biomedicine and Prevention, Section of Clinical Nutrition and Nutrigenomic, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

Lifestyle interventions remain the first-line treatment for non-alcoholic fatty liver disease (NAFLD), even if the optimal alimentary regimen is still controversial. The interest in antioxidants has increased over time, and literature reports an inverse association between nutrients rich in antioxidants and the risk of mortality due to non-communicable diseases, including NAFLD. Mediterranean diet (MD) is a model characterized by main consumption of plant-based foods and fish and reduced consumption of meat and dairy products. MD represents the gold standard in preventive medicine, probably due to the harmonic combination of many foods with antioxidant and anti-inflammatory properties. This regimen contributes substantially to the reduction of the onset of many chronic diseases as cardiovascular diseases, hypertension, type 2 diabetes mellitus, obesity, cancer, and NAFLD. The present review aims to clarify the intake of antioxidants typical of the MD and evaluate their effect on NAFLD.
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http://dx.doi.org/10.3390/ijerph16173011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747511PMC
August 2019

Novel Insights into the Genetic Landscape of Nonalcoholic Fatty Liver Disease.

Int J Environ Res Public Health 2019 08 1;16(15). Epub 2019 Aug 1.

Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico IRCCS, 20122 Milan, Italy.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide, is epidemiologically associated with overweight, insulin resistance features and type 2 diabetes, and can progress to advanced liver fibrosis and hepatocellular carcinoma. Genetic factors play an important role in the development of NAFLD, which is a multifactorial disease. Several common naturally occurring variants modulating lipid and retinol metabolism in hepatocytes predispose to NAFLD development and progression, in particular those in and . In addition, genetic variants that protect hepatic cells from oxidative stress modulate the susceptibility to progressive NAFLD. Although the molecular mechanisms linking these genetic variants with liver disease are not yet fully understood, hepatic fat has emerged as a major driver of the disease, while altered retinol metabolism and mitochondrial oxidative stress play a role in determining the development of advanced NAFLD.
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http://dx.doi.org/10.3390/ijerph16152755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695718PMC
August 2019

Urotensin II receptor expression in patients with ulcerative colitis: a pilot study.

Minerva Gastroenterol Dietol 2020 Mar 9;66(1):23-28. Epub 2019 Jul 9.

Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples, Italy.

Background: Urotensin II (U-II) is a vasoactive peptide that interacts with a specific receptor named UTR. Recently, our group has demonstrated increased UTR expression in both human colon adenocarcinoma cell lines and adenomatous polyps, as well as in colon carcinoma samples if compared to healthy colon samples of the same patients. We also showed that an UTR agonist induced an increase in colon adenocarcinoma cell growth in vitro, whereas the UTR block with a specific antagonist caused an inhibition of their growth and an inhibition of about 50% of both motility and cell invasion. Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) associated with an increased baseline risk for colon cancer compared with the general population, and this risk is mostly attributed to chronic inflammation and immune dysregulation. This risk increases along with the duration of the disease, as demonstrated by many studies. There are no UTR expression data related to UC, and we therefore evaluated UTR expression in ill colon biopsies and in healthy colon ones of patients with UC and colon biopsies of healthy patients.

Methods: We enrolled, prior to informed consent, 11 patients (5 males and 6 females, age range 29-75 years, median age 52 years) with first UC diagnosis compared to 11 healthy controls (6 males and 5 females, age range 30-78 years, median age 55 years). We have therefore sampled inflammatory and healthy tissue in UC patients. We have also taken colic tissue samples in healthy subjects. Evaluation of receptor expression was performed by reverse transcription-polymerase chain reaction (RT-PCR), Western Blot analysis. The ANOVA Test (P<0.05) was used for statistical analysis.

Results: We found: 1) increased expression of UTR in 11/11 UC patients with ill mucosa biopsies compared to healthy controls in RT-PCR and in Western Blot analysis; 2) increased UTR expression in 11/11 UC patients with ill colon biopsies compared to the results obtained from healthy colon biopsies of the same patients both in RT-PCR and in Western Blot analysis; 3) increased UTR expression in 9/11 UC patients healthy colon biopsy specimens compared to healthy controls.

Conclusions: UTR could be considered as an inflammatory UC disease marker because its expression is greater in the mucosa of ill colon than in the healthy colon of the same patients and compared to healthy controls.
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http://dx.doi.org/10.23736/S1121-421X.19.02602-3DOI Listing
March 2020
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