View clinical trials related to Liver Cirrhosis.
Filter by:Informed consent obtained from the patient or the patient's legal surrogate. The window for randomization and initiation of study drug infusion is 2 days from day of Admission. All further time points are relative to the day of randomization. Patients will be randomized (1:1) to receive either recombinant human GM-CSF or placebo. Using randomized block design of 10 each generated by computer and provided in sequential, sealed, opaque envelopes. Subjects will be stratified based on Child status. Patients who fulfil the inclusion criteria will receive either slow IV infusion of GM CSF (Sargamostatim-250mcg/M2) over 4 hour and inhalation of same dose by micronebulizer for 7 days OR Placebo(saline infusion and saline nebulization). Standard medical care will be given in both limbs.
Cirrhosis is characterized by loss of muscle as well as fat mass, which increases morbidity and mortality before, during, and after liver transplantation. A common mechanism for the reduced muscle and fat mass in cirrhosis is an increased expression of the TGF (transforming growth factor)beta superfamily member, myostatin, in the muscle and adipose tissue. The present study will examine the expression of myostatin, its receptor and intracellular signaling pathways in the skeletal muscle and mesenteric adipose tissue in cirrhotic patients undergoing liver transplantation as compared to healthy controls undergoing planned abdominal surgery. 16 cirrhotic patients will be identified from the transplant list, and 16 healthy controls from outpatient surgery lists. Nutritional assessment will be performed, including anthropometry (triceps skinfold thickness, mid arm circumference), dual energy x-ray absorptiometry (DEXA), and bioelectrical impedance analysis (BIA). Rectus abdominis muscle tissue and omental fat tissue will be harvested in the operating room, and the expression of signaling proteins involved in skeletal muscle protein synthesis will be quantified. The investigator will also quantify the expression of genes involved in lipolysis and lipid synthesis. The investigator anticipates that the expression of myostatin will be higher in the skeletal muscle and adipose tissue of cirrhotics as compared to controls. There will be a reduction in the expression of the signaling proteins that regulate skeletal muscle protein synthesis, as well as the expression of genes regulating lipogenesis. The increased expression of myostatin will also correlate with reduced anthropometric and DEXA measurements of lean body mass and fat mass.
Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.
Aim: To test if MRI can detect meaningful changes in portal pressure in the liver to assess whether treatment with beta-blockers has worked. Liver Disease: Most people with liver disease do not have symptoms. Over time they develop 'cirrhosis' - severe liver scarring. In the United Kingdom deaths due to cirrhosis have doubled over the last decade, because of increasing rates of alcohol consumption and obesity, while heart, kidney, lung diseases, strokes and cancer fatalities have fallen. Portal pressure: Cirrhosis causes increased pressure within the liver and changes in the circulation leading to the development of varicose veins in the gullet and stomach called 'varices'. Varices bleed easily, leading to emergency situations that can be life threatening. However, if the increased pressure within the liver (portal pressure) is detected early, then treatment can prevent variceal bleeding. The only test we have to predict prognosis and treatment success in someone with cirrhosis is by measuring the portal pressure. Measuring portal pressure: Currently the only existing test to measure portal pressure is to pass a pressure sensor through a vein in the neck, down into the liver. This is called the hepatic venous pressure gradient (HVPG) measurement. The HVPG measurement is disliked by patients because it is an invasive procedure. It is also expensive and not widely available. Hence, patients with cirrhosis need to have regular camera tests (endoscopies) to look for varices. How can you treat varices? Two options; 1. With tablets to lower the pressure (beta-blockers) 2. Endoscopy treatment (banding) Both have advantages and disadvantages; - Beta-blockers only lower the portal pressure in about half of those that take them, with some evidence they may also have a protective effect against infections from the bowel by increasing the speed of bowel motion - Treating the varices with endoscopy requires several endoscopies and can lead to life-threatening bleeding. Most patients are therefore given beta-blockers and monitored closely to see if they work. Why does it matter? Beta-blockers can cause side effects (e.g. fainting) that are unpleasant enough to make up to one third of patients stop taking them. Beta-blockers only reduce the portal pressure in half of patients. The remaining patients are exposed to potential side effects and possible harm in those with the most advanced liver disease. These patients may still have a life-threatening bleed as the varices have not been adequately treated. There is a desperate need to discover whether the portal pressure changes with treatment (such as with beta-blockers) without invasive tests across the NHS. Proposed study: Researchers in Nottingham have shown MRI can be used as an accurate marker of portal pressure with just one scan. To be useful to patients, doctors and researchers, this study will investigate whether MRI can detect meaningful changes in portal pressure after treatment with beta-blockers. This study has been designed with patient and public involvement (PPI) integrated throughout. A focus group shaped the study design and committed to collaborate in developing patient materials, recruitment, retention and dissemination. All patients who have HVPG will be given information about the study. Study Visit 1 - One hour MRI scan - Endoscopy to identify varices - If varices are present the patient will be started on beta-blockers and invited to visit 2 - If there are no varices, patients will return to regular follow up with the liver team Study Visit 2 (after one week) - Assess side effects, blood pressure and pulse - Increase dose of beta-blocker as appropriate Study Visit 3 (after 4-12 weeks) - One hour MRI scan - Repeat HVPG measurement Treatment success is determined by the second HVPG measurement. If beta-blockers are working they will be continued. If not, the patient will have treatment with endoscopy. This represents the ideal pathway which is more personalised than current standard care.
This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.
Low-dose continuous infusion of terlipressin will be administered to six cirrhotic patients with refractory ascites.
Hepatopulmonary Syndrome is a respiratory complication of liver cirrhosis defined as a triad: hypoxemia (PaO2 < 80 mmHg in room air), chronic liver disease and intrapulmonary vasodilatations. Its prevalence varies between 4 and 32%. Numerous treatments have been tried but the only efficient therapy to cure the syndrome is liver transplantation. Without transplantation it is associated with a higher mortality which is the reason why hepatopulmonary syndrome patients have a higher priority to transplantation. However it appears in some restricted studies that hepatopulmonary syndrome is associated with more postoperative complications (infections, vascular and biliary complications, prolonged length of mechanical ventilation…). The investigators hypothesised that hepatopulmonary syndrome patients have more postoperative complications after liver transplantation than non hepatopulmonary syndrome patients matched on age, MELD (Model for End-Stage Liver Disease) score, comorbidities, perioperative transfusion and noradrenaline doses.
To study the effect of ramelteon, a melatonin receptor agonist, on sleep quality, duration and cognitive function in cirrhotics with insomnia. Patients with cirrhosis have difficulties with their sleep quality, which adversely affects their health-related quality of life. It is assumed the sleep disturbances are related to hepatic encephalopathy (HE) in these patients. However, several recent reports have indicated that this is not a perfect concordance and that cognition is not related to sleep disturbance. The mechanism for this change is not clear, although there is evidence of melatonin-delayed phase in these patients as well as difficulties with the excretion pattern of cortisol. Ghrelin is an orexigenic hormone produced by the stomach which stimulates the appetite and also has a profound effect on sleep. Our group has demonstrated a substantial alteration in ghrelin secretion in cirrhosis that correlates with poor slow-wave sleep. In healthy individuals, ghrelin injection encourages slow-wave sleep while sleep deprivation increases ghrelin levels. The role of ghrelin in the sleep disturbances of cirrhosis has not been determined. Prior studies have also lacked the use of overnight polysomnography as a tool and have relied on either actigraphy or questionnaires. There is a need for detailed mechanistic and therapeutic approaches to analyzing sleep disturbances in cirrhosis. Also the therapy of sleep disturbance in cirrhosis is largely empirical. Prior studies have evaluated hydroxyzine which runs the risk of precipitating HE. Ramelteon is a melatonin analog that is FDA-approved for use in insomnia and will potentially be useful to restore the sleep-wake cycle in cirrhosis-associated sleep disturbance. The investigators aim to study the impact of the FDA-approved ramelteon on the sleep quality (using questionnaires and sleep diaries) on these patients with cirrhosis.
A Phase 3b, single arm, open-label, multicenter study in treatment naïve adults with chronic HCV infection and compensated cirrhosis to assess the safety of 8 weeks of treatment with glecaprevir/pibrentasvir and to demonstrate the efficacy of the sustained virologic response 12 weeks post dosing (SVR12) rates of 8 weeks of treatment with glecaprevir/pibrentasvir compared to the historical SVR12 rates of 12 weeks of treatment with glecaprevir/pibrentasvir.
This is a study that will evaluate the utility of measuring liver and spleen stiffness before and after a meal by a non invasive ultrasound based technologies called Fibroscan (Transient elastography) and acoustic radio-frequency impulse (ARFI) in diagnosing or excluding cirrhosis in patients with chronic liver disease who will be getting a liver biopsy.