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Topic Review
Pathogenesis of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a very complex world health problem. Approximately 905,677 new cases and 830,180 HCC-related deaths were reported in 2020. The estimation of more than 1 million deaths caused by HCC by 2030 has been predicted. The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated.
  • 761
  • 08 May 2023
Topic Review
Autophagy and Apoptosis
The pathogenesis of inflammatory bowel disease (IBD) implicates several interconnecting factors. Immunity and external factors interact, and most aspects are still under investigation. Autophagy and apoptosis are two critical pathways that decide the fate of the individual cells of the intestinal mucosa.
  • 761
  • 29 Nov 2023
Topic Review
Neuroendocrine Regulation in Liver Fibrosis
Liver fibrosis is a complicated process that involves different cell types and pathological factors. The excessive accumulation of extracellular matrix (ECM) and the formation of fibrotic scar disrupt the tissue homeostasis of the liver, eventually leading to cirrhosis and even liver failure. Myofibroblasts derived from hepatic stellate cells (HSCs) contribute to the development of liver fibrosis by producing ECM in the area of injuries. It has been reported that the secretion of the neuroendocrine hormone in chronic liver injury is different from a healthy liver. Activated HSCs and cholangiocytes express specific receptors in response to these neuropeptides released from the neuroendocrine system and other neuroendocrine cells. Neuroendocrine hormones and their receptors form a complicated network that regulates hepatic inflammation, which controls the progression of liver fibrosis.
  • 756
  • 06 Dec 2022
Topic Review
Janus-Faced Role of Autophagy in Hepatocellular Carcinoma
Autophagy is a multi-step catabolic process that occurs in cells at a basal level and is triggered by various stressors that disrupt cellular homeostasis. These stressors can include low levels of cellular ATP, nutrient and growth factor deficiencies, hypoxia, endoplasmic reticulum (ER) stress, pathogen entry, or exposure to anticancer drugs. 
  • 756
  • 21 Nov 2023
Topic Review
Medical Treatment of Gastroesophageal Reflux Disease
Gastroesophageal reflux disease has a high incidence and prevalence in the general population. Clinical manifestations are heterogenous, and so is the response to medical treatment. Proton pump inhibitors are still the most common agents used to control reflux symptoms and for healing esophagitis, but they are not a one-size-fits-all solution for the disease. Patients with persistent troublesome symptoms despite medical therapy, those experiencing some adverse drug reaction, or those unwilling to take lifelong medications deserve valid alternatives.
  • 753
  • 04 Jul 2023
Topic Review
Inflammatory Bowel Disease Biological Treatments
Inflammatory bowel disease (IBD) is a chronic disease that requires lifelong medication and whose incidence is increasing over the world. There is currently no cure for IBD, and the current therapeutic objective is to control the inflammatory process. Approximately one third of treated patients do not respond to treatment and refractoriness to treatment is common. Therefore, pharmacological treatments, such as monoclonal antibodies, are urgently needed, and new treatment guidelines are regularly published. 
  • 749
  • 03 Sep 2021
Topic Review
Osteoporosis/Sarcopenia in Chronic Liver Disease
The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease.
  • 748
  • 27 Apr 2021
Topic Review
Microvascular Thrombosis and Liver Fibrosis Progression
Fibrosis is a frequent consequence of organ injury. The formation of an extracellular matrix (ECM) depends on a complex cascade of cellular and molecular pathways, the chronic activation of which results in a sustained fibrogenic process that leads to structural changes and, ultimately, to dysfunction of the affected organ. Thus, fibrosis is a major contributor to organ failure in human pathophysiology.
  • 748
  • 06 Jul 2023
Topic Review
Genetic Alterations in Intraductal Papillary Mucinous Neoplasms
Intraductal papillary mucinous neoplasms (IPMN) are benign pancreatic cysts found in the ducts of the pancreas that have the potential to become malignant. Identifying IPMNs that have high potential to become pancreatic cancer may help prevent unnecessary surgery which is the definitive treatment of IPMNs. Whole exome and targeted sequencing were utilized to better characterize the genetic alterations in IPMNs. The most commonly mutated gene in IPMNs is KRAS with 50–80% of IPMNs harboring a KRAS mutation.
  • 746
  • 31 Mar 2023
Topic Review
Fibroblast Growth Factors for Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD), a chronic condition associated with metabolic dysfunction and obesity, has reached epidemic proportions worldwide. Although early NAFLD can be treated with lifestyle changes, the treatment of advanced liver pathology, such as nonalcoholic steatohepatitis (NASH), remains a challenge. There are currently no FDA-approved drugs for NAFLD. Fibroblast growth factors (FGFs) play essential roles in lipid and carbohydrate metabolism and have recently emerged as promising therapeutic agents for metabolic diseases. Among them, endocrine members (FGF19 and FGF21) and classical members (FGF1 and FGF4) are key regulators of energy metabolism. FGF-based therapies have shown therapeutic benefits in patients with NAFLD, and substantial progress has recently been made in clinical trials. These FGF analogs are effective in alleviating steatosis, liver inflammation, and fibrosis.
  • 743
  • 24 Apr 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.
  • 741
  • 09 Feb 2024
Topic Review
Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women
The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. 
  • 741
  • 24 Jan 2024
Topic Review
Lenvatinib for Hepatocellular Carcinoma
Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended to obtain a curative response in patients with a low tumor burden. This entry introduce the therapeutic response, management of adverse events, post-progression treatment after lenvatinib and treatment strategy for BCLC intermediate stage HCC.
  • 736
  • 12 Oct 2021
Topic Review
Role of the Immune System in IBD-Associated Cancer
Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown.
  • 735
  • 13 Dec 2021
Topic Review
Diagnosis of Cytomegalovirus Infection
Cytomegalovirus (CMV) infection is still a matter of concern in Inflammatory Bowel Diseases (IBD) patients, especially regarding the disease’s relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. 
  • 735
  • 10 Jan 2024
Topic Review
Endoscopic Vacuum Therapy in the Upper Gastrointestinal Tract
Anastomotic leaks after gastrointestinal surgery have an important impact on surgical outcomes because of the high morbidity and mortality rates. Multiple treatment options exist requiring an individualized patient-tailored treatment plan after multidisciplinary discussion. Endoscopic vacuum therapy (EVT) is a novel treatment option that is nowadays recognized as an effective and useful endoscopic approach to treat leaks or perforations in both the upper and lower gastrointestinal tract.
  • 734
  • 28 Jun 2023
Topic Review
Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases
Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients’ quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Cytokines have a central role in immune disorders and seem to be involved at different levels in the pathogenesis of articular and intestinal IMID, leading to the activation and perpetuation of proinflammatory pathways with consequent tissue damage.
  • 733
  • 28 Feb 2023
Topic Review
Sarcopenic Obesity in Liver Cirrhosis
The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle–liver–adipose tissue axis. 
  • 732
  • 20 Apr 2021
Topic Review
Therapeutic Options against Chronic HBV
Currently, Chronic Hepatitis B (CHB) is controlled but not cured by approved antivirals. For instance, transcriptionally active HBV DNA in the nucleus is not directly targeted. Except for interferon-α (IFN-α) and pegylated IFN-α, all other licensed drugs are nucleoside (Lamivudine, Clevudine, Entecavir, Telbivudine) and nucleotide analogues (Adefovir dipivoxil, Tenofovir disoproxil fumarate, Tenofovir alafenamide). All these drugs are potent at reducing viral loads and normalizing alanine transaminase levels in CHB patients. However, long-term treatment with many of these drugs leads to the development of multiple drug resistance mutations. In addition, while a limited reduction in cccDNA is achieved, long-term nucleos(t)ide analogue treatment does not reduce hepatitis B surface antigen (HBsAg) levels.
  • 730
  • 14 Jul 2021
Topic Review
Diabetes Mellitus and Gut Microbiota
The gut microbiota is a complex ecosystem consisting of bacteria, fungi, archaea, and viruses living in symbiosis with the human organism. This collection of bacteria, archaea, and eukaryotes that colonize the digestive system has developed this fascinating symbiotic relationship with its host over thousands of years, characterized by a complex mutually beneficial interaction.
  • 729
  • 02 Mar 2023
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