View clinical trials related to Fibrosis.
Filter by:Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage liver disease that is characterized by decreased arterial oxygenation caused by intrapulmonary vascular dilatation. Due to the different diagnostic criteria used in different studies, its prevalence ranges from 4% to 47% in patients with cirrhosis. Main underlaying pathogensis for HPS being activation of macrophages which are responsible for iNOS, PDGF and VEGF release contributing to development of intrapulmonary vascular dilatation(IPVD) , and neoangiogenesis leading to anatomical shunt resulting decreased oxygenation. Sphingosine 1 phosphate (S1P) is an essential compound produced and secreted by endothelial cells, platelets and RBC's. S1P prevents adhesion, transmigration and release of inflammatory mediators from macrophages. S1P levels are decreased in cirrhotics. Simvastatin, a HMG CoA inhibitor has many pleotropic effects, Of which one is by agonizing the S1P response and improving oxygenation in HPS patients. Simvastatin at a optimal dose of 40mg/day for 6months. Pre and post simvastatin treatment related oxygenation changes and concurrently its effect on liver fibrosis will be evaluated.
The aim of this prospective study is to evaluate the natural course and prognosis of hospitalized patients with liver cirrhosis.
The aim of this study was to developed and validated models to predict hepatic decompensation and survivals in pediatric patients with cirrhosis and compared these models with currently available models.
This is a single arm prospective pilot trial that evaluates the ability of a novel imaging agent (68Ga-FAP-2286) to identify pathologic fibrosis in the setting of hepatic, cardiac and pulmonary fibrosis. FAP-2286 is a peptide that potently and selectively binds to Fibroblast Activation Protein (FAP). FAP is a transmembrane protein expressed on fibroblasts and has been shown to have higher expression in idiopathic pulmonary fibrosis (IPF), cirrhosis, and cardiac fibrosis.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As an independent predictor of cardiovascular mortality, particularly for stroke, its management is a real public health issue. AF is associated with diabetes, obesity, hypertension, heart failure and, occasionally, hyperthyroidism. Atrial fibrosis is one of the major players in the genesis and maintenance of AF. It has a strong impact on rhythmic prognosis and treatment success. Currently the AF ablation is the treatment recommended by the European Society of Cardiology (ESC) and by the American Society of Cardiology. The rate of AF recurrence is variable according to the patient characteristics and remains unfortunately today difficult to predict. Abnormal concentrations of circulating biomarkers reflecting the underlying pathophysiologic mechanisms of myocardial fibrosis could help to identify patients at higher risk of developing AF and/or AF recurrence after ablation. Thus, the development of simple, reliable and valid biological tests of atrial fibrosis would allow the clinicians i) to estimate the potential success of AF ablation; ii) to predict AF recurrence; iv) and to propose a AF personalized therapeutic approach. The main objective of PROFIB-AF study is to identify, among biological markers (ICTP, PICP, PIIINP, sRAGE, AGE, Galectin 3, sSt2, microRNAs) of myocardial fibrosis, those which can predict the recurrence risk after AF ablation.
Chronic liver disease is a major healthcare problem in Hong Kong and worldwide. The diagnosis of liver fibrosis and inflammation in patients with chronic liver disease has important prognostic and therapeutic implications. The current gold standard to evaluate and stage the severity of liver fibrosis and inflammation is based on liver biopsies, which are invasive and impractical for screening and monitoring the disease. The existing non-invasive methods still have significant limitations to meet the challenge. Magnetic resonance effect can be used to obtain the molecular-level information on the biochemical properties of human tissues. The investigators will develop non-invasive quantitative MRI technologies to evaluate and stage liver fibrosis and inflammation. Our approaches are based on the endogenous contrast mechanism and thus do not need to inject an MRI contrast agent. Our approaches can be implemented on a regular MRI scanner and do not need any extra hardware. To enable the technology for routine clinical use, the investigators will develop fully automated post-processing techniques for the proposed MRI acquisition approaches. The investigators will perform multi-center clinical studies in Hong Kong and mainland China to validate our imaging measurements by histopathologic results from liver biopsies on patient cohorts.
Loss of skeletal muscle mass or sarcopenia is the most common and potentially reversible complication in cirrhosis that increases morbidity and mortality before, during and after liver transplantation. No proven treatments exist for the prevention or reversal of sarcopenia in cirrhosis, primarily because the mechanisms responsible for this are unknown. Based on compelling preliminary studies and those of the co investigator, investigators hypothesize that the mechanism of reduced skeletal muscle mass in cirrhosis is due to a myostatin mediated impaired mTOR (mechanistic target of rapamycin) signaling resulting in reduced protein synthesis and increased autophagy. Investigators further postulate that leucine, a direct stimulant of mTOR, will reverse the impaired mTOR phosphorylation in the skeletal muscle of cirrhotics. The consequent increase in protein synthesis reduced autophagy will result in an increase in skeletal muscle mass. Investigators will test these hypotheses by quantifying the response to acute and long term (3 month) administration of hydroxymethyl butyrate (HMB) enriched essential amino acid compared with an isonitrogenous isocaloric non-essential balanced amino acid mixture (does not stimulate protein synthesis) in cirrhotic patients. Fractional protein synthesis rate (FSR) in skeletal muscle, responses of the molecular regulatory pathways of skeletal muscle protein synthesis, and autophagy flux will be quantified in the acute and long term protocols. Tracer studies using L-[D5]-phenylalanine (Phe) as a primed constant infusion (prime 2µmol.kg-1.hr-1; constant 0.05 µmol.kg-1.hr-1) with and L [ring-D2] tyrosine, forearm plethysmography, and sequential skeletal muscle biopsies (total of 3 per study subject) will be used to quantify these outcomes. Anthropometric, clinical and body composition measures will be additional outcome measures for the long term intervention. Expression of regulatory signaling proteins, myostatin, IGF-1 (insulin like growth factor) , phospho-Akt, phospho-AMPK (activated protein kinase), phospho-mTOR and phospho-p70s6k will be quantified by Western immunoblots. Autophagy flux will be measured by quantifying expression of the autophagosome proteins.
Coronavirus disease 2019 (COVID-19) which is caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic. It is unclear whether the relatively low number of reported cases of COVID-19 in people with CF (pwCF) is due to enhanced infection prevention practices or whether pwCF have protective genetic/immune factors. This study aims to prospectively assess the proportion of pwCF, including both adults and children with CF who have evidence of SARS-CoV-2 antibodies over a two-year period. This study will also examine whether pwCF who have antibodies for SARS-CoV-2 have a different clinical presentation and what impact this has on their CF disease. The proposed study will recruit pwCF from paediatric and adult CF centres throughout the United Kingdom. Serological testing to detect antibodies will be performed on blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points if bloodwork is available via normal clinical care. Clinical data on, lung function, CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology and vaccination receipt, will be collected during routine clinical assessments. Associations will be examined between socio-demographic and clinical variables and serologic testing. The investigators will also examine the effects of SARS-CoV-2 infection on clinical outcomes and analyse end-points to explore any age-related or gender-based differences, as well as subgroup analysis of outcomes in lung-transplant recipients and pwCF receiving cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. As pwCF receive COVID-19 vaccination the investigators will perform a comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCF following natural infection and vaccination SARS-CoV-2 over time.
The main purpose of this study is to evaluate the safety and tolerance of umbilical cord mesenchymal stem cells (UCMSCs) in patients with decompensated alcoholic cirrhosis, and to provide dose basis for subsequent clinical study design. We will also explore the possible mechanism of UCMSCs in the treatment of decompensated alcoholic cirrhosis (DAC).
Chronic hepatitis B (CHB) affects 257million individuals worldwide. In 2017, it caused around 39.7 million cases of cirrhosis and 0.4 million cirrhosis-related deaths in 2017. However, there is no specific treatment for liver fibrosis/cirrhosis. Although nucleos(t)ide analogues (NAs) profoundly suppress viral replication, fibrosis/cirrhosis progression can still occur in NA-treated patients. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that may prevent fibrosis/cirrhosis progression by reducing hepatic steatosis/inflammation, dampening renin-angiotensin aldosterone system (RAAS) activation, and reducing fluid retention, effects of which are independent of glycemic control. Clinical studies in diabetic patients show SGLT2 inhibitors reduce hepatis steatosis/inflammation, regress ascites (a cirrhotic complication), and improve liver function parameters and survival prognosis in terms of model for end-stage liver disease (MELD) score. There are currently no randomized controlled trials (RCTs) on role of SGLT2 inhibitors in preventing fibrosis/cirrhosis progression in CHB patients. Magnetic resonance elastography (MRE) and transient elastography (TE) are non-invasive techniques for liver stiffness measurement (LSM), although MRE is more accurate than TE. The investigators propose a double-blind, randomized, placebo-controlled trial to compare effect of empagliflozin (an SGLT2 inhibitor) with placebo (1:1 ratio) in preventing fibrosis progression in both diabetic and non-diabetic NA-treated CHB patients with significant/advanced fibrosis or compensated cirrhosis. 108 patients will be randomly sampled from our pre-existing TE database. Empagliflozin 10mg daily will be given to treatment arm. Placebo pills will be manufactured identical in appearance to empagliflozin. Subjects will receive active or placebo pills for three years, and undergo clinical, anthropometric and laboratory assessments (at baseline, weeks 8, 16, and every 4 months thereafter). They will undergo LSM by TE at baseline, end of first, second and third year, and by MRE at baseline and end of third year. Primary outcome is difference in change to liver stiffness (measured by MRE) from baseline between the two groups at the end of third year. The study results will determine whether SGLT2 inhibitors can prevent hepatic fibrosis/cirrhosis progression in NA-treated CHB patients.