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Topic Review
Pathophysiological Mechanisms of Metabolic-Associated Liver Disease
Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. 
  • 252
  • 19 Jan 2024
Topic Review
Pathophysiology of Cholangiopathies
Cholestasis is a condition characterized by decrease in bile flow due to progressive pathological states that lead to chronic cholestatic liver diseases which affect the biliary tree at the intrahepatic and extrahepatic level. Cholestasis can pose risks to overall health, as the reduced flow of bile can hinder the absorption of fat-soluble vitamins and nutrients, leading to deficiencies. Additionally, it can induce other complications other such as cirrhosis, liver failure, malignancies and bone disease. Early diagnosis and adequate management are crucial in treating cholestasis in order to alleviate symptoms, prevent complications and address the underlying cause.
  • 438
  • 20 Jun 2023
Topic Review
Pathophysiology of Extra-Intestinal Manifestations in Inflammatory Bowel Diseases
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are complex multifactorial chronic inflammatory disorders affecting nearly 7 million patients worldwide, with an increasing prevalence in Northern Europe and emerging countries. IBD can be associated with a wide spectrum of extra-intestinal manifestations (EIMs) with a significant impact on patients’ quality of life. The pathophysiology of EIMs in IBD is intricate and uncertain. The European Crohn’s and Colitis Organization (ECCO) proposed an operational definition of EIMs’ pathology in IBD patients.
  • 118
  • 16 Jan 2024
Topic Review
Pathophysiology of Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) encompasses a group of heterogeneous diseases that entail chronic, relapsing gastrointestinal tract inflammation of inexactly known etiology and pathogenesis. IBD is clinically classified as Crohn’s disease (CD) or ulcerative colitis (UC) based on symptoms, disease location, and histopathological characteristics.
  • 884
  • 28 Jan 2023
Topic Review
Pathophysiology of NAFLD
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus.
  • 911
  • 27 Apr 2022
Topic Review
Pathophysiology of Nitrergic Enteric Neurons
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. 
  • 541
  • 23 Jun 2021
Topic Review
PD-1/PD-L1 Therapy in Non-alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is characterized by an enhanced activation of the immune system, which predispose the evolution to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Resident macrophages and leukocytes exert a key role in the pathogenesis of NAFLD. In particular, CD4+ effector T cells are activated during the early stages of liver inflammation and are followed by the increase of natural killer T cells and of CD8+ T cytotoxic lymphocytes which contribute to auto-aggressive tissue damage. To counteract T cells activation, programmed cell death 1 (PD-1) and its ligand PDL-1 are exposed respectively on lymphocytes and liver cells’ surface and can be targeted for therapy by using specific monoclonal antibodies, such as of Nivolumab, Pembrolizumab and Atezolizumab.
  • 715
  • 22 Mar 2022
Topic Review
PD-L1
The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this entry, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.
  • 813
  • 22 Dec 2020
Topic Review
PD-L1 Expression as a Biomarker in Gastric Cancer
Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Unfortunately, molecular heterogeneity and, consequently, acquired resistance in GC are the major causes of failure in the development of biomarker-guided targeted therapies. However, by showing promising survival benefits in some studies, the recent emergence of immunotherapy in GC has had a significant impact on treatment-selectable procedures. Immune checkpoint inhibitors (ICIs), widely indicated in the treatment of several malignancies, target inhibitory receptors on T lymphocytes, including the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and release effector T-cells from negative feedback signals. 
  • 366
  • 26 Sep 2023
Topic Review
Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide and its incidence is rising. Percutaneous locoregional therapies, such as radiofrequency ablation and microwave ablation, are widely used as curative treatment options for patients with small HCC, but their effectiveness remains restricted because of the associated high rate of recurrence, occurring in about 70% of patients at five years. These thermal ablation techniques have the particularity to induce immunomodulation by destroying tumours, although this is not sufficient to raise an effective antitumour immune response. Ablative therapies combined with immunotherapies could act synergistically to enhance antitumour immunity. 
  • 291
  • 09 Sep 2022
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