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Topic Review
Influence of Gut–Liver Axis on Portal Hypertension
Clinically significant portal hypertension is associated with most complications of advanced chronic liver disease (ACLD), including variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Gut dysbiosis is a hallmark of ACLD with portal hypertension and consists of the overgrowth of potentially pathogenic bacteria and a decrease in autochthonous bacteria; additionally, congestion makes the intestinal barrier more permeable to bacteria and their products, which contributes to the development of complications through inflammatory mechanisms within the gut–liver axis. The identification of the gut–liver liver-axis-related metabolic and molecular pathways may serve as a target for new therapeutic strategies through the modulation of the intestinal environment.
  • 416
  • 01 Sep 2022
Topic Review
Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease
Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome.
  • 413
  • 23 Dec 2022
Topic Review
Fecal Microbiota Transplantation in Inflammatory Bowel Disease
Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT). As the use, safety and effectiveness of FMT for recurrent Clostridioides difficile infection (CDI) has increased in recent years, it has also demonstrated real clinical benefits for treating SARS-CoV-2 and CDI co-infection. As a result of immune dysregulation, Crohn's disease and ulcerative colitis cause damage to the digestive tract.
  • 413
  • 10 May 2023
Topic Review
JAK-STAT Pathway in Immune Checkpoint Inhibitor-Induced Colitis Patients
Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. 
  • 410
  • 08 Feb 2024
Topic Review
Diet–Microbiota Interplay in Macrophage Plasticity and Intestinal Health
Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract with an increasing prevalence worldwide. Macrophages, innate immune cells that exhibit high plasticity, perpetuate inflammatory signalling in IBD through excessive release of inflammatory mediators. In recent years, pioneering research has revealed the importance of the interplay between macrophages and gut microbiota in maintaining intestinal homeostasis. Particular attention is focusing on microbiota-derived metabolites, believed to possess immunomodulatory properties capable of manipulating macrophage plasticity. Microbiota-derived short-chain fatty acids (SCFAs) and indole compounds, along with dietary sourced omega-3 (ω-3) polyunsaturated fatty acids (PUFA), exert anti-inflammatory effects, attributable to interactions with macrophages.
  • 406
  • 27 May 2022
Topic Review
“Small Hepatocytes” in the Liver
Mature hepatocytes (MHs) in an adult rodent liver are categorized into the following three subpopulations based on their proliferative capability: type I cells (MH-I), which are committed progenitor cells that possess a high growth capability and basal hepatocytic functions; type II cells (MH-II), which possess a limited proliferative capability; and type III cells (MH-III), which lose the ability to divide (replicative senescence) and reach the final differentiated state. These subpopulations may explain the liver’s development and growth after birth. Generally, small-sized hepatocytes emerge in mammal livers. The cells are characterized by being morphologically identical to hepatocytes except for their size, which is substantially smaller than that of ordinary MHs. We initially discovered small hepatocytes (SHs) in the primary culture of rat hepatocytes.
  • 406
  • 21 Dec 2023
Topic Review
Equol Production Status and Nonalcoholic Steatohepatitis
Equol is a metabolite of daidzein, a major soybean isoflavone with estrogenic and antioxidant activities. As the production of equol depends on the presence of certain members of the intestinal microflora, not all individuals can produce equol. Treatment with equol-rich soy product, SE5-OH markedly attenuated the development of liver fibrosis and the expression of alpha-smooth muscle actin in obese OLETF rats, and in the clinical study, the degree of fibrosis and ballooning in equol nonproducers was significantly higher than that of producers in women with NASH. In addition, the percentage of nonproducers with NAS ≥ 5 was significantly higher than that of producers in women with NASH. 
  • 405
  • 19 Nov 2021
Topic Review
Pancreatic Disorders in Inflammatory Bowel Diseases
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation.
  • 404
  • 25 May 2023
Topic Review
Hepatobiliary Impairments in Patients with Inflammatory Bowel Diseases
Inflammatory bowel disease (IBD) refers to chronic conditions with a low mortality but high disability. The multisystemic nature of these diseases can explain the appearance of some extraintestinal manifestations, including liver damage. Abnormal liver biochemical tests can be identified in approximately one third of patients with IBD and chronic liver disease in 5% of them. Among the liver diseases associated with IBD are primary sclerosing cholangitis, cholelithiasis, fatty liver disease, hepatic amyloidosis, granulomatous hepatitis, drug-induced liver injury, venous thromboembolism, primary biliary cholangitis, IgG4-related cholangiopathy, autoimmune hepatitis, liver abscesses or the reactivation of viral hepatitis. The most common disease is primary sclerosing cholangitis, a condition diagnosed especially in patients with ulcerative colitis.
  • 403
  • 12 Jan 2023
Topic Review
Dietary and Nutritional Support in Esophageal Diseases
The esophagus is the centerpiece of the digestive system of individuals and plays an essential role in transporting swallowed nutrients to the stomach. Diseases of the esophagus can alter this mechanism either by causing anatomical damage that obstructs the lumen of the organ (e.g., peptic, or eosinophilic stricture) or by generating severe motility disorders that impair the progression of the alimentary bolus (e.g., severe dysphagia of neurological origin or achalasia). In all cases, nutrient assimilation may be compromised. In some cases (e.g., ingestion of corrosive agents), a hypercatabolic state is generated, which increases resting energy expenditure.
  • 401
  • 24 Nov 2022
Topic Review
Prognostic and Predictive Biomarkers in Familial Breast Cancer
Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. 
  • 399
  • 15 Mar 2023
Topic Review
Non-Coding RNAs in Hepatocellular Carcinoma Progression
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. 
  • 399
  • 01 Nov 2023
Topic Review
Contrast-Enhanced Endoscopic Ultrasonography
Endoscopic ultrasound can be useful for obtaining detailed diagnostic images for pancreatic disease. Contrast-enhanced harmonic endoscopic ultrasound has allowed to demonstrate not only microvasculature but also real perfusion imaging using second-generation contrast agents. Furthermore, endoscopic ultrasound fine-needle aspiration cytology and histology have become more ubiquitous.
  • 396
  • 27 Jun 2022
Topic Review
Definition and Diagnosis of Barrett’s Esophagus
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett’s esophagus (BE) is a known precursor of esophageal adenocarcinoma. 
  • 395
  • 14 Apr 2023
Topic Review
Association between Pancreatitis and Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with poor prognosis, leading to significant cancer-related mortality and an overall five-year survival rate of about nine percent. 
  • 393
  • 27 Jan 2022
Topic Review
Pathophysiological Mechanisms of Anemia in Chronic Liver Disease
Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. 
  • 392
  • 23 Aug 2023
Topic Review
Gut Microbiota and Leaky Gut in Food Allergy
Food allergies (FAs) are pathological immune reactions triggered by normally innocuous food protein antigens. Gut microbiota are one of the main actors in the complex mechanism of sensitization. The term “leaky gut” defines a status of weakening or disruption of the intestinal barrier, in which substances that are normally confined in the intestinal cavity pass through the intestinal wall and enter the bloodstream. Leaky gut has garnered significant interest due to its potential role in the onset of FA.
  • 391
  • 09 Feb 2024
Topic Review
MicroRNAs in Hepatic Ischemia–Reperfusion Injury
Hepatic ischemia–reperfusion injury (IRI) is one of the main factors for early allograft dysfunction (EAD), which may lead to graft rejection, graft loss, or shortened graft life in liver transplantation. Hepatic IRI appears to be inevitable during the majority of liver procurement and transportation of donor organs, resulting in a cascade of biological changes. The activation of signaling pathways during IRI results in the up- and downregulation of genes and microRNAs (miRNAs). miRNAs are ~21 nucleotides in length and well-characterized for their role in gene regulations; they have recently been used for therapeutic approaches in addition to their role as biomarkers for many diseases. Various miRNAs have been identified in association with hepatic IRI that either exaggerate or ameliorate the hepatic IRI. Altering targeted miRNA expression has great potential to reduce early graft dysfunction and improve patient outcome. Strategies to implement this approach have been studied using hepatic cell lines subjected to oxygen deprived conditions in vitro, as well as animal models after induction of hepatic IRI through warm ischemia in vivo. By studying the mechanisms of specific miRNAs, the up- or downregulation during hepatic IRI reveals whether that miRNA can ameliorate or exaggerate the metabolism and functions of the liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels can be used to indicate when liver injury is present and improve diagnosis accuracy along with miRNA biomarkers. The manipulation of miRNAs could have an influence on the inflammatory and oxidative stress pathways associated with hepatic IRI.
  • 389
  • 15 Apr 2022
Topic Review
Hepatitis B Virus-Associated Hepatocellular Carcinoma
Hepatitis B virus (HBV) affects around 300 million people worldwide and is a significant risk factor for the development of hepatocellular carcinoma (HCC). Nucleos(t)ide analog therapy has aided in decreasing mortality from HBV.
  • 389
  • 21 Feb 2024
Topic Review
Ileal Pouch–Anal Anastomosis and Pouchitis
Inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common.
  • 388
  • 18 Jul 2022
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