Search results for "PROGRESS"
showing 10 items of 1620 documents
The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B.
2017
Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patien…
Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disea…
2016
Background The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition. Aim To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy. Methods In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach. Results Median follow-up was 36 months (IQR 24–77). Twenty-five patients (18%) showed some amelioration, 63 (53%) had stability, 30 (25…
PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices
2019
Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…
Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model
2016
BACKGROUND & AIMS No published study to date has provided a careful analysis of the effects of a sustained viral response (SVR) on the outcomes of patients with compensated hepatitis C virus (HCV)-related cirrhosis in relation to the degree of portal hypertension. Therefore, we estimated the impact of achieving SVR on disease progression, hepatocellular carcinoma (HCC) development and mortality in a large cohort of HCV patients with cirrhosis with or without oesophageal varices (OVs) at the start of antiviral therapy. METHODS A total of 535 Caucasian patients were prospectively recruited to this study. All patients had a clinical or histological diagnosis of compensated HCV-related cirrhosi…
Myeloid cells do not contribute to gender-dependent differences in disease outcome in murine cutaneous leishmaniasis.
2015
Gender-associated differences in the outcome of infections are well known. Apart from behavior-released differences in their incidence, immunological factors also contribute to disease outcome. The underlying mechanisms are often unknown. Here, we show that in murine experimental leishmaniasis, female mice develop larger skin lesions that harbor significantly more parasites, exhibit increased parasite dissemination to visceral organs associated with a shift towards T helper (Th) 2 immunity with increased levels of IL-4. Antigen presenting cells (APC) responsible for T cell priming, such as macrophages or dendritic cells, were not involved in the process. Additionally, in adoptive transfer e…
Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin.
2021
Abstract Background Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced…
Lifespan Changes of the human brain in Alzheimer's disease
2018
[EN] Brain imaging studies have shown that slow and progressive cerebral atrophy characterized the development of Alzheimer's Disease (AD). Despite a large number of studies dedicated to AD, key questions about the lifespan evolution of AD biomarkers remain open. When does the AD model diverge from the normal aging model? What is the lifespan trajectory of imaging biomarkers for AD? How do the trajectories of biomarkers in AD differ from normal aging? To answer these questions, we proposed an innovative way by inferring brain structure model across the entire lifespan using a massive number of MRI (N = 4329). We compared the normal model based on 2944 control subjects with the pathological …
Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity.
2017
Background & Aims Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m2. We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. Methods We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatit…
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
2019
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational …
2019
Abstract Background Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. Methods The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adve…