Fecal Microbiota Transplantation in NAFLD Treatment.

Introduction: Gut microbiota is not only a taxonomic biologic ecosystem but is also involved in human intestinal and extra-intestinal functions such as immune system modulation, nutrient absorption and digestion, as well as metabolism regulation. The latter is strictly linked to non-alcoholic fatty liver disease (NAFLD) pathophysiology. Materials and methods: We reviewed the literature on the definition of gut microbiota, the concepts of "dysbiosis" and "eubiosis", their role in NAFLD pathogenesis, and the data on fecal microbiota transplantation (FMT) in these patients. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, eubiosis, dysbiosis, bile acids, NAFLD, and FMT. Results: Gut microbiota qualitative and quantitative composition is different in healthy subjects vs. NALFD patients. This dysbiosis is associated with and involved in NAFLD pathogenesis and evolution to non-acoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). In detail, microbial-driven metabolism of bile acids (BAs) and interaction with hepatic and intestinal farnesoid nuclear X receptor (FXR) have shown a determinant role in liver fat deposition and the development of fibrosis. Over the use of pre- or probiotics, FMT has shown preclinical and initial clinical promising results in NAFLD treatment through re-modulation of microbial dysbiosis. Conclusions: Promising clinical data support a larger investigation of gut microbiota dysbiosis reversion through FMT in NAFLD using randomized clinical trials to design precision-medicine treatments for these patients at different disease stages.

Onion Polyphenols as Multi-Target-Directed Ligands in MASLD: A Preliminary Molecular Docking Study.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in the high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyzes, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, liver receptors X α and ß, as well as peroxisome proliferator-activated receptors α and γ. In this study, for the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19). METHODS: Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes. RESULTS: The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material. CONCLUSIONS: Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.

Mediterranean Diet: The Beneficial Effects of Lycopene in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) presents the most common chronic liver disease globally; it is estimated that 25.24% of the world's population has NAFLD. NAFLD is a multi-factorial disease whose development involves various processes, such as insulin resistance, lipotoxicity, inflammation, cytokine imbalance, the activation of innate immunity, microbiota and environmental and genetic factors. Numerous clinical studies have shown that the Mediterranean diet produces beneficial effects in NAFLD patients. The aim of this review is to summarize the beneficial effects of lycopene, a soluble pigment found in fruit and vegetables, in NAFLD.

Gut Microbiota in Non-Alcoholic Fatty Liver Disease Patients with Inflammatory Bowel Diseases: A Complex Interplay.

The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn's disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn's disease, and ulcerative colitis.

Clinical Patterns of Primary Biliary Cholangitis: Comparison Between Two European Case Series.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive destruction of the intrahepatic bile ducts, followed by fibrous substitution of the ducts and potential evolution in cirrhosis. The geographical disparity in the prevalence of PBC suggests a possible role of environmental factors in developing the disease. We analyzed two groups of patients with different geographical prevalence. METHODS: This study concerned the analysis of 14 Caucasian patients in two groups: ten patients enrolled in the Digestive Diseases Unit, University of Catanzaro (Italy), and four patients enrolled in the Department of Hepatology, University Hospital Kràlovskè Vinohrady of Prague (Czech Republic). The statistical analysis was performed using the software IBM SPSS (v. 20, Windows). RESULTS: The Italian group showed a statistically significant difference in the total bilirubin values at diagnosis and during the last control (0.74±0.267 vs. 0.56±0.246; p-value: 0.013). Moreover, the comparison between the two groups showed a statistically significant difference in the serum albumin values at the time of the last control (4.6±0.231 vs. 4.15±0.532; p-value: 0.048). CONCLUSION: Our data indicate an effective difference in the onset and clinical presentation between our two groups. More epidemiologic, prospective, and multicenter research projects are warranted to advance PBC knowledge in Europe.

Hepatic Encephalopathy by Manganese Deposition: A Case Report and a Review of Literature.

BACKGROUND: Hepatic encephalopathy is defined as a spectrum of neuropsychiatric disorders in patients with liver dysfunction, usually cirrhosis, after exclusion of brain disease. This study reports the role of manganese in brain alterations and therefore in clinical manifestations of hepatic encephalopathy. CASE PRESENTATION: Male patient, 67 years old, suffering from alcoholic liver cirrhosis and two previous episodes of hepatic encephalopathy, developed drowsiness, asterixis, amnesia, disorientation in time and space, and psychomotor retardation. Brain MRI without contrast showed: initial signs of cerebral atrophy, a hyperintense signal of globi pallidi and bilateral substantia nigra. The hyperintense signal of globi pallidi is the result of manganese deposition in the brain. CONCLUSION: The case report presented supports the data reported in the literature indicating that the increase in plasma manganese levels in subjects with liver dysfunction is correlated with the onset of extrapyramidal symptoms.

Nutritional Support in Acute Liver Failure.

Acute liver failure (ALF) presents with an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The clinical course leads to the development of coagulopathy and hepatic encephalopathy. The role of nutrition in its prevention and treatment remains uncertain. We aimed to review literature data on the concept of ALF and the role of nutrition in its treatment and prevention, considering the impact of gut microbiota dysbiosis and eubiosis. We conducted a review of the literature on the main medical databases using the following keywords and acronyms and their associations: liver failure, nutrition, branched-chain amino acids, gut microbiota, dysbiosis, and probiotics. Upon their arrival at the emergency department, an early, accurate nutritional assessment is crucial for individuals with ALF. Branched-chain amino acids (BCAAs), stable euglycemia maintenance, and moderate caloric support are crucial for this subset of patients. An excessive protein load must be avoided because it worsens hepatic encephalopathy. Preclinical evidence supports future probiotics use for ALF treatment/prevention. Nutritional support and treatment for ALF are crucial steps against patient morbidity and mortality. BCAAs and euglycemia remain the mainstay of nutritional treatment of ALF. Gut dysbiosis re-modulation has an emerging and natural-history changing impact on ALF.

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease.

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.

SARS-CoV-2 Spread Dynamics in Italy: The Calabria Experience.

INTRODUCTION: The first case of infection by SARS-CoV-2 (i.e., COVID-19) has been officially recorded by the Italian National Health Service on February 21st, 2020. Lombardy was the first Italian region to be affected by the pandemic. Subsequently, the entire Northern part of Italy recorded a high number of cases, while the South was hit following the migratory waves. On March 8th, the Italian Government has issued a decree that imposed a total lockdown, defining it as a state of isolation and restricting access in Lombardy and the other 14 provinces of Northern Italy. METHODS: We analyzed the virus trend in the period between February 24th and September 8th, 2020, focusing on Calabria, with regards to the following items: new positives, change of total positives, and total cases. Furthermore, we included other information, such as the incubation period, symptom resolution period, quarantine period. RESULTS: On March 27th, the epidemic curve spiked with 101 new positive cases validating the hypothesis that this abnormal event was related to the displacement of non-residents people, living in the Northern part of Italy, to the home regions in the South. The epidemic curve showed a decreasing trend in the period after lockdown, proving the effectiveness of this measure. From the end of the lockdown May 04th to September 8th, the registered trend was -94.51%. A negative growth rate indicates that the number of new positive cases is lower than the number of healed patients. CONCLUSION: This study describes the effectiveness of the Italian Government policy, particularly the role of lockdown, for the containment of SARS-CoV-2 contagion in Calabria, a region with a low SARS-CoV-2 infection rate within the registered period.

Anxiety and Gastrointestinal Symptoms Related to COVID-19 during Italian Lockdown.

The first case of infection by SARS-CoV-2 (i.e., COVID-19) was officially recorded by the Italian National Health Service on 21 February 2020. Respiratory tract manifestations are the most common symptoms, such as gastrointestinal symptoms (GISs) like nausea or sickness, diarrhea, and anorexia, and psychological effects may be reported in affected individuals. However, similar symptoms may be observed in healthy people as a consequence of an anxiety state. METHODS: We analyzed GISs and anxiety state during the COVID-19 lockdown period; from 9 March 2020 to 4 May 2020. A web-based survey consisting of 131 items was administered to 354 students affiliated with the School of Medicine of the University "Magna Graecia" of Catanzaro; Italy. A set of statistical analyses was performed to analyze the relationships among the answers to assess a correlation between the topics of interest. RESULTS: The statistical analysis showed that 54.0% of interviewed reported at least one GISs, 36.16% of which reported a positive history for familial GISs (FGISs). The 354 subjects included in our cohort may be stratified as follows: 25.99% GISs and FGISs, 27.97% GISs and no-FGISs, 10.17% no-GISs and FGISs, 35.87% no-GISs and no-FGISs. Results indicated an anxiety state for 48.9% of respondents, of which 64.74% also presented GISs. In addition, considered dietary habits, we detect the increased consumption of hypercaloric food, sweetened drinks, and alcoholic beverages. CONCLUSIONS: The increase of GISs during the lockdown period in a population of medical students, may be correlated to both dietary habits and anxiety state due to a concern for one's health.

Primary Biliary Cholangitis and Bile Acid Farnesoid X Receptor Agonists.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by the progressive destruction of the intrahepatic bile ducts. Currently, the first line drug for PBC is ursodeoxycholic acid (UDCA) characterized by anti-apoptotic, anti-inflammatory and protective actions on cholangiocytes. Despite its recognized therapeutic action, 30-40% of PBC patients only partially benefit from UDCA therapy. This has led to the identification of the role of the farnesoid x receptor (FXR) in cholestatic liver diseases and, consequently, to the development of obeticholic acid (OCA), a steroid FXR agonist that has been recently approved for the treatment of PBC. OCA though is not effective in all patients and can cause itch, which eventually induces treatment drop out. Therefore, the search for new therapeutic strategies for PBC has begun. This review, in addition to summarizing the current treatments for PBC, provides overview of the chemical characteristics of new steroid FXR agonist candidates that could represent a future perspective for the treatment of PBC.