274 research outputs found
Supplemental material for Safety of vedolizumab in liver transplant recipients: A systematic review
No full textSupplemental Material for Safety of vedolizumab in liver transplant recipients: A systematic review by Marco Spadaccini, Alessio Aghemo, Flavio Caprioli, Ana Lleo, Federica Invernizzi, Silvio Danese and Maria F Donato in United European Gastroenterology Journal</p
Role of cholangiocytes in primary biliary cirrhosis
No full textPrimary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the development and progression of the disease are still controversial and largely undefined. Evidence suggests that PBC results from an articulated immunologic response against an immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes show specific immunobiological features that are responsible for the selective targeting of those cells by the immune system. The immune reaction in PBC selectively targets small sized, intrahepatic bile ducts; although a specific reason for that has not been defined yet, it has been established that the biliary epithelium displays a unique heterogeneity, for which the physiological and pathophysiological features of small and large cholangiocytes significantly differ. In this review article, the authors provide a critical overview of the current evidence on the role of cholangiocytes in the immune-mediated destruction of the biliary tree that characterizes PBC
Clinical update on risks and efficacy of anti-SARS-CoV-2 vaccines in patients with autoimmune hepatitis and summary of reports on post-vaccination liver injury
No full text: Patients with liver diseases, especially those with cirrhosis, have an increased mortality risk when infected by SARS-CoV-2 and therefore anti-SARS-CoV-2 vaccine has been recommended by leading Scientific Associations for all patients with chronic liver diseases. However, previous reports have shown a reduced antibody response following the full course of vaccination in immunosuppressed patients, including liver transplant recipients and several rheumatic diseases. This document, drafted by an expert panel of hepatologists appointed by the Italian Association for the Study of the Liver (AISF), aims to present the updated scientific data on the safety and efficacy of anti-SARS-CoV-2 mRNA vaccines in patients with autoimmune hepatitis (AIH). Furthermore, given the recent reports of sporadic cases of AIH-like cases following anti-SARS-CoV-2 mRNA vaccines, we summarize available data. Finally, we provide experts recommendations based on the limited data available
Cancer-on-chip: a 3D model for the study of the tumor microenvironment
No full textAbstract The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans
Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals
No full textBACKGROUND:
Despite the dramatic improvement in viral eradication rates that has been reached with direct antiviral agents (DAAs), the real benefit of viral eradication after DAAs on hepatocellular carcinoma (HCC) development is still controversial.
AIM:
To prospectively assess the risk of HCC occurrence and early recurrence in a large cohort of DAA-treated HCV-cirrhotic patients and to identify potential predictors of HCC development.
METHODS:
We analyzed data prospectively collected from 1927 consecutive HCV-infected cirrhotic patients treated with DAA from January to December 2015 in 10 tertiary liver centers in Italy and followed-up for one year after therapy. 161 patients had a previous HCC.
RESULTS:
38/161 subjects developed tumor recurrence during the follow-up (recurrence rate = 24.8 per 100-year), patients with SVR had a significantly lower rate of recurrence. Lack of SVR and alpha-fetoprotein (AFP) were independent predictors of HCC recurrence. 50/1766 patients without a previous HCC history developed HCC during follow-up (incidence rate = 2.4 per 100-year). Lack of SVR was the strongest predictor of HCC development. Furthermore, patients with SVR and no stigmata of portal hypertension have a lower incidence rate of HCC (1.0 per 100-year).
CONCLUSIONS:
SVR is associated with a significant decrease of recurrent or de novo HCC. Baseline AFP and signs of portal hypertension can help to stratify the risk of HCC
Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells
No full textIn the last years, several studies have been focused on elucidate the role of tumor microenvironment (TME) in cancer development and progression. Within TME, cells from adaptive and innate immune system are one of the main abundant components. The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth. This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Liver is well-known to be an important immunological organ with unique microenvironment. Here, in normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as liver sinusoidal endothelial cells and Kupffer cells, favoring self-tolerance against gut antigens. The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells, in order to understand how this cross-talk promotes tumor growth. Deeper attention is, in fact, focused on immune-based therapy for these tumors, as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment. In this review, we will examine the key pathways underlying TME cell-cell communications, with deeper focus on the role of natural killer cells in primary liver tumors, such as HCC and iCCA, as new opportunities for immune-based therapeutic strategies
The consequences of apoptosis in autoimmunity
No full textThe clearance of apoptotic cells is a highly regulated mechanism, normally associated with antiinflammatory
response. During early stages of apoptosis the cell is promptly recognized and engulfed by
professional phagocytes or tissue cells to avoid the outflow of intracellular content and limit the
immunological reaction against released antigens. However, increasing evidences suggest that impairment
in the uptake of apoptotic cell debris is linked to the development of autoimmunity. In fact,
autoantigens have been demonstrated to be content within apoptotic bodies and apoptotic cells seems to
be critical in the presentation of antigens, activation of innate immunity and regulation of macrophage
cytokine secretion.
We herein review the known mechanisms for regulating the uptake of the products of apoptosis in the
development of autoimmunity
lleo meconial
No full textThe term Meconium Ileus refers to three different conditions of similar pathologic anatomy and clinicalfeatures. but very different prognosis and ·treatment. The author describes: 1) Classic Meconium Ileus and its complications being an affection of high inmediate, mediate and latemortality. 2) The Meconium Plug Síndrome of easy resolution and good prognosis when ever correct diagnosis is established. 3) Meconium obstruction in the absence of mucoviscidosisa rare afection associa ted with intestinal absortive anomalies and whose prognosis is better than of Classic Meconium Ileus.El término ileo meconial comprende tres entidades nosológicas con similitud anatomoclínica pero que difieren en su pronóstico y tratamiento.Se describen: el I. M. Clásico y sus complicaciones con su elevado porcentaje de mortalidad inmediata, mediata y tardía. El síndrome del tapón meconial defácil resolución y buen pronóstico una vez diagnosticado. Por último, el I. M. no asociado a mucoviscidosis, afección rara relacionada con trastornos disabsortivosy cuyo pronóstico es más favorable que el I M. Clásico
Mediterranean Diet and NAFLD: What We Know and Questions That Still Need to Be Answered
No full textNon-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is expected to become the leading cause of end-stage liver disease worldwide over the next few decades. In fact, NAFLD encompasses different clinical scenarios, from the simple accumulation of fat (steatosis) to steatohepatitis (NASH), NASH-cirrhosis, and cirrhosis complications. In this context, it is fundamental to pursue strategies aimed at both preventing the disease and reducing the progression of liver fibrosis once liver damage is already initiated. As of today, no pharmacological treatment has been approved for NAFLD/NASH, and the only recommended treatment of proven efficacy are life-style modifications, including diet and physical exercise pointing at weight loss of 5%–7%. Different dietetic approaches have been proposed in this setting, and in this review, we will discuss the evidence regarding the efficacy of the Mediterranean Diet as a treatment for NAFLD. In particular, we will report the effects on liver-related outcomes
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