Search results for "hepatology"

Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated ‘in vivo’ by surgical procedure with interest in liver transplantation

2019

AIM Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels. METHODS hIL10 gene was hydrofected by retrograde hydrodynamic inject…

Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.

2016

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents…

Between reality and the guidelines: A survey on perception, diagnosis and management of hepatic encephalopathy in 201 Italian specialist centres

2017

Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

2021

Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis …

Interferon lambda 4 rs368234815 TT>δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease

2017

Background and Aims: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients. Methods: We considered 946 consecutive Italian individuals at risk of NASH wit…

Molecular bases of the poor response of liver cancer to chemotherapy

2018

Summary A characteristic shared by most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in adults, and in a lesser extent hepatoblastoma (HB) mainly in children, is their high refractoriness to chemotherapy. This is the result of synergic interactions among complex and diverse mechanisms of chemoresistance (MOC) in which more than 100 genes are involved. Pharmacological treatment, although it can be initially effective, frequently stimulates the expression of MOC genes, which results in the relapse of the tumor, usually with a more aggressive and less chemosensitive phenotype. Identification of the MOC genetic signature accounting fo…

Integrative Genome-Scale DNA Methylation Analysis of a Large and Unselected Cohort Reveals 5 Distinct Subtypes of Colorectal Adenocarcinomas

2019

BACKGROUND & AIMS: Colorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of the CpG island methylator phenotype (CIMP) is not clear. METHODS: Genome-scale methylation and transcript expression were measured by DNA Methylation and RNA expression microarray in 216 unselected colorectal cancers, and findings were validated using The Cancer Genome Atlas 450K and RNA sequencing data. Mutations in epigenetic regulators were assessed using CIMP-subtyped Cancer Genome Atlas exomes. RESULTS: CIMP-high cancers dichotomized into CIMP-H1 and CIMP-H2 based on methylation profile. KRAS mutation was associated significantly with CIMP-H2 cancers, but not CIMP-H1 can…

Autoimmune diseases and 8.1 ancestral haplotype: an update

2018

The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid haplotype carried by most people who type for HLA-B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome-wide-association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within …

Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study.

2018

Abstract Introduction Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. Aim To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. Patients and methods Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th–75th IQR). Results Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3…

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.

2019

Background & Aims Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. Methods C57BL/6 (control), Myd88–/–, Ticam1–/–, and Il15–/– mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and int…