1,721,170 research outputs found
Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma
No full textVarious grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug
Diagnosis and treatment of small intestinal bacterial overgrowth
No full textA huge number of bacteria are hosted in the gastrointestinal tract, following a gradient increasing towards the colon. Gastric acid secretion and intestinal clearance provide the qualitative and quantitative partitioning of intestinal bacteria; small intestinal bacteria overgrowth (SIBO) occurs when these barrier mechanisms fail. Diagnosis of SIBO is challenging due to the low specificity of symptoms, the frequent association with other diseases of the gastrointestinal tract and the absence of optimal objective diagnostic tests. The therapeutic approach to SIBO is oriented towards resolving predisposing conditions, and is supported by antibiotic treatment to restore the normal small intestinal microflora and by modifications of dietary habits for symptomatic relief. In the near future, metagenomics and metabolomics will help to overcome the uncertainties of SIBO diagnosis and the pitfalls of therapeutic management, allowing the design of a personalized strategy based on the direct insight into the small intestinal microbial community
GUT MICROBIOTA IN PRIMARY SCLEROSING CHOLANGITIS: FROM PROGNOSTIC ROLE TO THERAPEUTIC IMPLICATIONS
No full textBackground: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acids metabolism, inflammation and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way. Summary: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons. Key messages: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role, and the therapeutic implications
Management of hepatitis C virus infection recurrence after liver transplantation: an overview
No full textHepatitis C virus (HCV) infection is the major indication for liver transplantation worldwide. Its recurrence is virtually universal. Once reinfection is established, progression to cirrhosis occurs in 25%-30% of recipients within 5 years. Several studies have attempted to identify the ideal antiviral treatment for liver transplant recipients. At present, the management of recurrent HCV infection in liver transplant recipients is based on widely accepted indications, which represent a reliable guide to identify the "ideal" candidate for therapy, when therapy should be started, and what is to be expected in terms of side effects and response to treatment
Physiology and pathophysiology of liver lipid metabolism
No full textLiver lipid metabolism and its modulation are involved in many pathologic conditions, such as obesity, non-alcoholic fatty liver disease, diabetes mellitus, atherosclerosis and cardiovascular disease. Metabolic disorders seem to share a similar background of low-grade chronic inflammation, even if the pathophysiological mechanisms leading to tissue and organ damage have not been completely clarified yet. The accumulation of neutral lipids in the liver is now recognized as a beneficial and protective mechanism; on the other hand, lipoperoxidation is involved in the development and progression of non-alcoholic steatohepatitis. The role of the gut microbiota in liver lipid metabolism has been the object of recent scientific investigations. It is likely that the gut microbiota is involved in a complex metabolic modulation and the translocation of gut microflora may also contribute to maintaining the low-grade inflammatory status of metabolic syndrome. Therefore, lipid metabolism pathology has vague limits and complex mechanisms, and the knowledge of these is essential to guide diagnostic and therapeutic decisions
Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?
Get PDFAlterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC. Mitochondria-derived vesicles (MDVs), a subpopulation of EVs, are another missing link in the comprehension of the molecular mechanisms underlying the onset and progression of HCC biology. EVs have been involved in HCC growth, dissemination, angiogenesis, and immunosurveillance escape. The contribution of MDVs to these processes is presently unclear. Pyroptosis triggers systemic inflammation through caspase-dependent apoptotic cell death and is implicated in tumor immunity. The analysis of this process, together with MDV characterization, may help capture the relationship among HCC development, mitochondrial quality control, and inflammation. The combination of immune checkpoint inhibitors (i.e., atezolizumab and bevacizumab) has been approved as a synergistic first-line systemic treatment for unresectable or advanced HCC. The lack of biomarkers that may allow prediction of treatment response and, therefore, patient selection, is a major unmet need. Herein, we overview the molecular mechanisms linking mitochondrial dysfunction, inflammation, and pyroptosis, and discuss how immunotherapy targets, at least partly, these routes
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