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Topic Review
Risk Factors for NAFLD-Related Hepatocellular Carcinoma
Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% in the future. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD.
  • 203
  • 23 Nov 2023
Topic Review
Immunotherapy in MS-Stable Colorectal Cancer
Immunotherapy is an innovative treatment that is highly effective against certain cancers, such as skin and lung cancer. However, for colorectal cancer, one of the most prevalent cancers, it does not benefit most patients. Recent research suggests that by treating liver metastases first, immunotherapy might become effective for those with colorectal cancer.
  • 250
  • 22 Nov 2023
Topic Review
The Liver-Centric Role in Insulin Resistance
The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies.
  • 137
  • 22 Nov 2023
Topic Review
Major Genetic Factors Involved in Liver Diseases Pathogenesis
Over the past century, our genetic background has not changed, but chronic diseases are on the rise globally. In addition to the genetic component, the critical factors for many diseases are lifestyle, eating changes, exposure to drugs, xenobiotics, alcohol, smoking, polluted air, etc. These techniques include genome-wide association studies (GWAS) that allow the identification of unknown genetic risk factors, positional cloning of unknown genes associated with different diseases, the gene tests for single nucleotide variants (SNVs), and next-generation sequencing (NGS) of selected genes or/and the entire genome. Gut microbiome composition and its metabolites are not only regulating factors in carcinogenesis (including de novo after liver transplantation) but also in xenobiotics and anticancer treatment failure, observations that may be related to the genetic background of the individuals.
  • 670
  • 21 Nov 2023
Topic Review
TLR4 Signaling in Hepatocellular Carcinoma Immunotherapy
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. Immunotherapy has emerged as the mainstay treatment option for unresectable HCC. Toll-like receptor 4 (TLR4) plays a crucial role in the innate immune response by recognizing and responding primarily to bacterial lipopolysaccharides. In addition to its role in the innate immune system, TLR4 has also been implicated in adaptive immunity, including specific anti-tumor immune responses. In particular, the TLR4 signaling pathway seems to be involved in the regulation of several cancer hallmarks, such as the continuous activation of cellular pathways that promote cell division and growth, the inhibition of programmed cell death, the promotion of several invasion and metastatic mechanisms, epithelial-to-mesenchymal transition, angiogenesis, drug resistance, and epigenetic modifications. Emerging evidence further suggests that TLR4 signaling holds promise as a potential immunotherapeutic target in HCC
  • 412
  • 21 Nov 2023
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. 
  • 388
  • 21 Nov 2023
Topic Review
Estrobolome and Hepatocellular Adenomas
Hepatocellular adenoma (HCA) or hepatic adenoma is defined as a benign liver lesion, seen in patients with excessive exposure to estrogen (the higher the dose of estrogen therapy, the higher the risk of HCA), genetic and metabolic syndromes or who have undergone anabolic androgen therapy. It is known that the estrobolome plays an important role in the human endocrine system; specifically relevant in the metabolization of estrogen are bacterial species producing β-glucuronidase (GUS) enzymes.
  • 150
  • 20 Nov 2023
Topic Review
Microbiome Influences Neurodevelopment in the Central Nervous System
The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the central nervous system (CNS) environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes. 
  • 200
  • 17 Nov 2023
Topic Review
Cystic Fibrosis Gastroenterologist's Transition from Pediatrics to Adult
Cystic Fibrosis is a chronic disease affecting multiple systems, including the GI tract. Clinical manifestation in patients can start as early as infancy and vary across different age groups. With the advent of new, highly effective modulators, the life expectancy of people with CF (PwCF) has improved significantly. Various GI aspects of CF care, such as nutrition, are linked to an overall improvement in morbidity, lung function and the quality of life of PwCF. The variable clinical presentations and management of GI diseases in pediatrics and adults with CF should be recognized. Therefore, it is necessary to ensure efficient transfer of information between pediatric and adult providers for proper continuity of management and coordination of care at the time of transition. 
  • 134
  • 17 Nov 2023
Topic Review
Hepatocellular Carcinoma in Non-Fibrotic Liver
Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion’s large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function.
  • 187
  • 15 Nov 2023
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