Exploring the link: Porto-sinusoidal vascular disorder and inflammatory bowel disease - A comprehensive narrative review.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions involving the portal venules and sinusoids, independent of the presence of portal hypertension (PH), and for which liver biopsy is essential for diagnosis. PSVD has been shown to be common in patients with immune-mediated diseases, including inflammatory bowel disease (IBD). The association between PSVD and the use of thiopurines and thioguanine in patients with IBD has been well established. In addition, research suggests an association between PSVD and IBD, even in cases where patients haven't been exposed to specific medications, probably related to changes in intestinal permeability. The identification and management of patients with known IBD and PSVD is a challenge for gastroenterologists. This narrative review aims to summarize the currently available data on the association between IBD and PSVD and provide practical suggestions for the management of this group of patients.

Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis.

Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow's triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.

Gut Microbiota and Neuroinflammation in Acute Liver Failure and Chronic Liver Disease.

Acute liver failure and chronic liver disease are associated with a wide spectrum of neurological changes, of which the best known is hepatic encephalopathy (HE). Historically, hyperammonemia, causing astrocyte swelling and cerebral oedema, was considered the main etiological factor in the pathogenesis of cerebral dysfunction in patients with acute and/or chronic liver disease. However, recent studies demonstrated a key role of neuroinflammation in the development of neurological complications in this setting. Neuroinflammation is characterized by activation of microglial cells and brain secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, which alter neurotransmission, leading to cognitive and motor dysfunction. Changes in the gut microbiota resulting from liver disease play a crucial role in the pathogenesis of neuroinflammation. Dysbiosis and altered intestinal permeability, resulting in bacterial translocation and endotoxemia, are responsible for systemic inflammation, which can spread to brain tissue and trigger neuroinflammation. In addition, metabolites derived from the gut microbiota can act on the central nervous system and facilitate the development of neurological complications, exacerbating clinical manifestations. Thus, strategies aimed at modulating the gut microbiota may be effective therapeutic weapons. In this review, we summarize the current knowledge on the role of the gut-liver-brain axis in the pathogenesis of neurological dysfunction associated with liver disease, with a particular focus on neuroinflammation. In addition, we highlight emerging therapeutic approaches targeting the gut microbiota and inflammation in this clinical setting.

Cellular therapies in liver and pancreatic diseases.

Over the past two decades, developments in regenerative medicine in gastroenterology have been greatly enhanced by the application of stem cells, which can self-replicate and differentiate into any somatic cell. The discovery of induced pluripotent stem cells has opened remarkable perspectives on tissue regeneration, including their use as a bridge to transplantation or as supportive therapy in patients with organ failure. The improvements in DNA manipulation and gene editing strategies have also allowed to clarify the physiopathology and to correct the phenotype of several monogenic diseases, both in vivo and in vitro. Further progress has been made with the development of three-dimensional cultures, known as organoids, which have demonstrated morphological and functional complexity comparable to that of a miniature organ. Hence, owing to its protean applications and potential benefits, cell and organoid transplantation has become a hot topic for the management of gastrointestinal diseases. In this review, we describe current knowledge on cell therapies in hepatology and pancreatology, providing insight into their future applications in regenerative medicine.

Clinical Implications of Helicobacter pylori Antibiotic Resistance in Italy: A Review of the Literature.

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a "high priority" pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment.

Humoral Predictors of Malignancy in IPMN: A Review of the Literature.

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5-9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.