A story of liver and gut microbes: How does the intestinal flora affect liver disease? A review of the literature

Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy

MicroRNAs as Regulators of Neo-Angiogenesis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly vascularized neoplasm. In the tumor niche, abundant angiogenesis is fundamental in providing nutrients for tumor growth and represents the first escape route for metastatic cells. Active angiogenesis, together with metastasis, are responsible for the reduction of recurrence-free survival of HCC. MicroRNAs (miRNAs) are small non-coding RNAs that have recently drawn attention in molecular targeted therapy or as diagnostic and prognostic biomarkers. MiRNA expression in HCC has been widely studied in the last decade. Some miRNAs have been found to be up- or down-regulated, besides association with apoptosis, metastasis progression and drug resistance have been found. This review article aims to summarize the angiogenetic process in tumor diseases and to update on what has been found in the vast world of HCC-related-miRNAs and, eventually, to report the latest finding on several miRNAs involved in HCC angiogenesis. We searched the state of the arts for the 12 miRNAs found to be involved with angiogenesis in HCC (miR-29b, miR-126-3p, miR-144-3p, miR-146a, miR-195, miR-199a-3p, miR-210-3p, miR-338- 3p, mir-491, mir-497, mir-638, mir-1301) and reported their main molecular targets and their overall effect in the sprouting of new vessels

Peritoneal Tuberculosis during Infliximab Treatment in a Patient with Ulcerative Colitis Despite a Negative Quantiferon Test

Infliximab is an IgG1 antitumor necrosis factor monoclonal antibody that is commonly used to treat inflammatory bowel disease (IBD) and other autoimmune disorders. However, it is known to increase the risk of reactivation of latent tuberculosis (LTBI) due to its capability to disrupt TB granulomas. We describe a case of extrapulmonary TB in a patient with ulcerative colitis who was treated with Infliximab after a negative Quantiferon Test. In addition, we report briefly on the current controversy about the appropriateness, interval, and methods for the repeated screening of latent TB in IBD patients that are treated with antitumor necrosis factor alpha (TNF-\u3b1) antibodies

Weighted miRNA co-expression networks analysis identifies circulating miRNA predicting overall survival in hepatocellular carcinoma patients

The weighted gene co-expression network analysis (WGCNA) has been used to explore gene expression datasets by constructing biological networks based on the likelihood expression profile among genes. In recent years, WGCNA found application in biomarker discovery studies, including miRNA. Serum samples from 20 patients with hepatocellular carcinoma (HCC) were profiled through miRNA 3.0 gene array and miRNAs biomarker candidates were identified through WGCNA. Results were validated by qRT-PCR in 102 HCC serum samples collected at diagnosis. WGCNA identified 16 miRNA modules, nine of them were significantly associated with the clinical characteristics of the patient. The Red module had a significant negative correlation with patients Survival (-\u20090.59, p\u2009=\u20090.007) and albumin (-\u20090.52, p\u2009=\u20090.02), and a positive correlation with PCR (0.61, p\u2009=\u20090.004) and alpha-fetoprotein (0.51, p\u2009=\u20090.02). In the red module, 16 circulating miRNAs were significantly associated with patient survival. MiR-3185 and miR-4507 were identified as predictors of patient survival after the validation phase. At diagnosis, high expression of circulating miR-3185 and miR-4507 identifies patients with longer survival (HR 2.02, 95% CI 1.10-3.73, p\u2009=\u20090.0086, and HR of 1.75, 95% CI 1.02-3.02, p\u2009=\u20090.037, respectively). Thought a WGCNA we identified miR-3185 and miR-4507 as promising candidate biomarkers predicting a longer survival in HCC patients

COVID-19-Induced Thrombosis in Patients without Gastrointestinal Symptoms and Elevated Fecal Calprotectin: Hypothesis Regarding Mechanism of Intestinal Damage Associated with COVID-19

Background: Patients with coronavirus infectious disease 2019 (COVID-19) and gastrointestinal symptoms showed increased values of fecal calprotectin (FC). Additionally, bowel abnormalities were a common finding during abdominal imaging of individuals with COVID-19 despite being asymptomatic. The current pilot study aims at evaluating FC concentrations in patients without gastrointestinal symptoms. Methods: we enrolled 25 consecutive inpatients with COVID-19 pneumonia, who were admitted without gastrointestinal symptoms and a previous history of inflammatory bowel disease. Results: At admission, 21 patients showed increased FC with median values of 116 (87.5; 243.5) mg/kg despite absent gastrointestinal symptoms. We found a strong positive correlation between FC and D-Dimer (r = 0.745, p < 0.0001). Two patients developed bowel perforation. Conclusion: our findings may change the current understanding of COVID-19 intestinal-related disease pathogenesis, shedding new light on the potential role of thrombosis and the consequent hypoxic intestinal damag

You Talking to Me? Says the Enteric Nervous System (ENS) to the Microbe. How Intestinal Microbes Interact with the ENS

Mammalian organisms form intimate interfaces with commensal and pathogenic gut microorganisms. Increasing evidence suggests a close interaction between gut microorganisms and the enteric nervous system (ENS), as the first interface to the central nervous system. Each microorganism can exert a different effect on the ENS, including phenotypical neuronal changes or the induction of chemical transmitters that interact with ENS neurons. Some pathogenic bacteria take advantage of the ENS to create a more suitable environment for their growth or to promote the effects of their toxins. In addition, some commensal bacteria can affect the central nervous system (CNS) by locally interacting with the ENS. From the current knowledge emerges an interesting field that may shape future concepts on the pathogen\u2013host synergic interaction. The aim of this narrative review is to report the current findings regarding the inter-relationships between bacteria, viruses, and parasites and the ENS

The Role of Liver and Spleen Elastography in the Screening of Esophageal Varices in Patients with Liver Cirrhosis: Do We Really Need Endoscopy?

Background: recently, the Baveno VI guidelines have suggested that esophagogastroduodenoscopy (EGD) to stage esophageal varices can be avoided in patients with advanced liver disease who have a liver stiffness (LS) 150x103/\u3bcL. Our study aims to analyze spleen stiffness (SS) as a non\u2010invasive method of diagnosis for clinically significant portal hypertension in order to avoid EGD in low\u2010risk patients for esophageal varices. We also want to compare the SS to other non\u2010invasive techniques and analyze their reproducibility and inter\u2010observer concordance. Patients and Methods: in this prospective study, we detected the SS and LS in 150 patients diagnosed with liver cirrhosis to be submitted for endoscopic screening for esophageal varices. In addition, we enrolled 70 healthy control individuals, who for other reasons, had undergone an endoscopic examination of the upper digestive tracts and who were negative for hepatic and lymphoproliferative disease. The discriminatory capacity for the presence of esophageal varices of the SS has been compared with that deriving from other non\u2010invasive procedures (LS, splenic diameter, splenic surface, platelet count, and combined scores deriving from these parameters). Optimal SS cut\u2010offs were sought to exclude the presence of varices. Particular emphasis was placed on the search for possible correlations of the with ultrasound parameters of portal hypertension and platelet count. Finally, we studied in a double\u2010blind fashion inter\u2010operator concordance with 50 measurements for LS, and 25 for SS. Results: cirrhotic patients have significantly higher SS and LS values than controls. The SS values were higher in cirrhotic patients with varices (n = 62) compared to patients without esophageal varices (n = 88) and to healthy controls (p <0.001). SS showed an AUROC of 0.93 (95% C.I., 0.89\u20100.97), statistically different from the other predictors (p <0.001). The cut\u2010off, chosen according to Youden\u2019s Index and equal to 38.55 kPa, showed sensitivity of 87%, specificity of 89%, NPV of 91%, and PPV of 84%. Instead, the cut\u2010off of 30.79 kPa has 100% sensitivity and 100% NPV. The cut\u2010off of 69.73 kPa demonstrated specificity and PPV of 100%. The SS demonstrated weak linear correlation with the splenic dimensions (bipolar diameter and surface measured at the organ\u2019s hilum). Moreover, it has a linear correlation with the platelet count, which was greater than that present with LS (r = 0.5 vs r = 0.32). The test revealed an excellent intraclass correlation coefficient (ICC) equal to 0.96 for SS and 0.97 for LS. Conclusion: the results of this study show how the SS can play an important role in the daily clinical management of cirrhotic patients. The SS (alone or combined with other indicators) may play an important role as a non\u2010invasive screening test for predicting the risk of varices

BCG infection (BCGitis) following intravesical instillation for bladder cancer and time interval between treatment and presentation: A systematic review

Objective: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment in non 12 12muscle-invasive bladder cancer, however,extravesical BCG infection may occur in remote organs as a potentially serious complication. Researchers aimed to assess whether a differ-ent timing of BCG infection after intravesical administration of BCG could be identified and estimated for each single involved organ.Methods: We performed a systematic literature review over systemic and genitourinary BCG infection case reports, including 271 publishedcase reports for a total of 307 patients. Demographic data, clinical features, and timing of BCG infection development were collected andanalyzed for each patient.Results: BCG infection developed with a different timing from last instillation, depending on the involved organ.Among the genitourinary complications, penile lesions occurred as early as 1 (1;3) weeks, while orchiepididymitis occurred as late as 56(6.25;156) weeks. At the same time, granulomatous hepatitis and lungs involvement such as miliary pulmonary BCG infection occurred ear-lier, with a median time of 1 (1;4) and 1 (1;6) weeks respectively, whereas vascular, osteoarticular, and muscular complications developedwith a median timing from last instillation of 52 (20;104), 68 (14;156), and 93 (29;156) weeks, respectively. The analysis detected a clusterbetween lungs, liver, and bone marrow complications on one side and muscular and osteoarticular or vascular complications on the otherside was also observed.Conclusions: BCG infection after intravesical BCG for bladder cancer may develop even several months or yearsafter the last instillation, depending on the involved organs. When BCG infection interests one or more organ, 2 main associative patternsare common: one involving lungs, liver, and bone marrow, with earlier occurrence but lower rates of microbiological diagnosis achieve-ment, and one involving muscular and osteoarticular or vascular districts, with later occurrence but higher rates of microbiological evidence

Monitoring neonatal fungal infection with metabolomics

The objective of our study was to evaluate the capability of the metabolomics approach to identify the variations of urine metabolites over time related to the neonatal fungal septic condition. The study population included a clinical case of a preterm neonate with invasive fungal infection and 13 healthy preterm controls. This study showed a unique urine metabolic profile of the patient affected by fungal sepsis compared to urine of controls and it was also possible to evaluate the efficacy of therapy in improving patient health

The role of elastography in alcoholic liver disease: fibrosis staging and confounding factors, a review of the current literature

INTRODUCTION: Alcohol-related liver disease (ALD) was estimated to have a prevalence of 2% among the USA population. Since severe fibrosis in compensated patients is the main predictor of long-term survival, it is of utmost importance to early detect patients with severe fibrosis before decompensation occurs. Liver elastography has been used to stage liver fibrosis. However, there is a widespread lack in guidelines for the correct use of liver stiffness (LS) in ALD. EVIDENCE ACQUISITION: A structured search was carried out on MEDLINE/PubMed database. From the original 225 research articles identified, only 12 studies met the inclusion criteria, with 10 studies being eventually included. EVIDENCE SYNTHESIS: According to reported data, patients with aspartate aminotransferase (AST)>100 IU/L and 50 IU/L showed significantly higher values of LS if compared to patients with the same fibrosis stage. Also, excessive alcohol consumption greatly influences elastography, leading to false fibrosis staging. When LS values >5-6 kPa are detected, several aspects should be taken into account. First of all, the patient should be asked about the current alcohol consumption (i.e. active vs. abstinence, determination of abstinence period, and quantification of alcohol intake), and if the patient is an active drinker, liver elastography can be repeated after a complete abstinence period of at least two weeks. and if the patient is an active drinker, liver elastography can be repeated after a complete abstinence period of at least two weeks. Secondly, clinicians should check liver transaminases level, and if AST are above 100 IU/L, they should be aware of a possible overestimation of fibrosis. However, whether transaminases-adapted cut-off values should be used for ad-hoc decisions in patients with no time or option to withdraw from alcohol consumption is still a matter of debate. CONCLUSIONS: We hope that our review article may serve as a reference point in the prospect of futures guidelines