Active clinical trials for "Liver Failure"

HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet. In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, the drug metabolism characteristics of TAF will be explored in such severe liver injury population of HBV-ACLF.

This study is to investigate MER receptor tyrosine kinase (MERTK) signalling cascade on monocytes and tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, acute-on-chronic liver failure (ACLF)) and in comparison to patients with acute liver failure and to healthy controls.

The project is essential to understand the impact of the COVID-19 pandemic in patients with Chronic Liver Disease (CLD). The impact has been felt due to direct risk of COVID infection in self, or in caregivers, lack of access to services during lockdown, interruptions in transplant listing and waitlist mortality. Briefly, the following points will be focused during the study. Long haul COVID-19 related symptoms. Impact on health and delay in interventions or drug therapy due to interruption of physical outpatient services. Impact on emergency admissions due to refractory ascites, new decompensation, variceal bleeding etc Impact on delayed transplant listing and waitlist mortality Impact on post-transplant patients with lack of access to drug monitoring/ physical OPD Impact on delay in interventions due to hepatobiliary malignancy. Effects of COVID-19 infection, vaccination (single dose, two doses) and no vaccination and protective antibody levels in patients with chronic liver disease and post-transplant recipients. Determination of dose protocol and need for booster vaccination in patients with CLD and post liver transplant recipients.

The goal of this observational study is oo compare the pharmacokinetic parameters of different tacrolimus containing medications in liver transplant patients. The main question[s] it aims to answer are: Differences in pharmacokinetic parameters of tacrolimus containing medicinal products (TL, TDD and their ratio - C/D) Changes in liver function parameters compared to baseline. Change in the estimated glomerular filtration rate (eGFR) compared to baseline. To assess the possible relation of liver function parameters and eGFR to C/D (blood concentration and daily dosage) Incidence of acute graft rejection during the study Incidence of BK and cytomegalovirus (CMV) infection during the study To assess the intraindividual variability of the TL, TDD and the ratios of these parameters (C/D) To assess the patient-adherence of therapy based on the BAASIS questionnaire, and prescription filled by individual patients, based on electronic health-care record. Participants will not have to undergo any additional clinical visits or tests except which are required in routine clinical care

Pediatric acute liver failure (PALF) is associated with very high mortality and morbidity with native liver survival varying between 21 to 75%.Hyperammonemia manifesting as hepatic encephalopathy and causing cerebral edema isresponsible for poor neurological outcome in ALF. Ammonia lowering measures have led to improvement in HE and higher native liver survival. L-ornithine L-aspartate (LOLA), a salt of natural amino-acids ornithine and aspartate, is an importantammonia scavenging drug. It acts as a substrate for urea cycle in liver and also converts ammonia to glutamine in perivenous hepatocytes as well as in the muscles.This drug has been shown to reduce ammonia and improve hepatic encephalopathy in cirrhoticadults.However, the issue with this drug is that the glutamine formed can reconvert to ammonia by the action of glutaminase, possibly, the reason why it failed to show decrease in ammonia and improvement in native liver survival in a randomized controlled trial in adult ALF. In western countries, ornithine phenylacetate has been used where ornithine converts ammonia to glutamine and phenylacetate then binds to this glutamine to form phenylacetylgutamine and eliminates it. Therapeutic plasma exchange (TPE), both high volume and standard volume has been shown to improve native liver survival in adults with ALF and is the standard of care in management of ALF and a grade 1 recommendation by all eminent liver societies.TPE leads to decreased ammonia. Although rate of ammonia formation is multiple times higher than rate of ammonia removal by plasmapheresis, this ammonia reduction is an indirect effect of glutamine removal by TPE. Glutamine, thus, acts as a reservoir for clearance of ammonia (in muscles and perivenous hepatocytes).In contrast to adults, the response to therapeutic plasma exchange has not been as encouraging inchildren, yet, most centers continue to use it based on recommendations in adults. Based on the knowledge that LOLA converts ammonia to glutamine and TPE clears glutamine from plasma, the investigators hypothesize that LOLA would act in synergestic way with TPE to lower ammonia levels, resulting in improvement in HE and better native liver survival in pediatric ALF. The goal of this clinical trial is to compare L-ornithine L-aspartate and therapeutic plasma exchange versus plasma exchange alone in lowering ammonia and improving outcomes in patients with pediatric acute liver failure.

Acute Liver Failure in children is associated with high mortality without liver transplantation. In addition, donor organ shortage makes it difficult to provide this treatment to every potential patient. Liver transplantation is life-saving but it carries the risk of major surgery and complications from lifelong anti-rejection drugs to suppress the immune system. If bridged across the immediate crisis following acute liver failure, the immense regenerative potential of the liver means that the patient's own liver may 're-grow'. This period is very time sensitive. Unfortunately, if the vital synthetic and detoxification function of the liver is not provided, the patient will often die before the liver can re-grow. Transplantation of liver cells (hepatocytes) can provide this 'bridge' with considerable advantages over whole organ transplantation. Firstly, hepatocytes are derived from donor livers which are otherwise unsuitable for transplantation. Secondly, unlike whole organs, they can be frozen and stored, thus act as an 'off the shelf' treatment. Thirdly, the technique of hepatocyte transplantation within microbeads coated with alginate (a gel originating from seaweed) and infused into the abdominal cavity is much less invasive than liver transplantation. Finally, the alginate protects the cells against the body's immune system, avoiding the need for immunosuppressive drugs and the associated major risks. Furthermore, preclinical work in King's College Hospital has shown that the addition of support cells called mesenchymal stromal cells (MSCs), can significantly improve the ability of hepatocytes to survive and function within the alginate microbead. The HELP trial is a Phase 1/2 safety and tolerability study of infusion of HMB002 (an optimal combination of hepatocytes and mesenchymal stromal cells put together in peptide-alginate microbeads) into paediatric patients with acute liver failure. This novel cellular therapy may act as a bridge treatment to liver transplant or lead to regeneration of the native liver.

ACLF is a syndrome characterized by rapid deterioration of liver function in chronic liver disease or undiagnosed chronic liver disease, with a high risk of short-term death. Both CMA and EASL mentioned that there is currently lack of specific drugs and treatment of liver failure. For patients with ACLF who are still graded as 2 or 3 after active medical treatment and/or artificial liver therapy, and the CLIF-C score is less than 64 points, it is recommended to perform liver transplantation as soon as possible within 28 days. Early liver transplantation is crucial for improving the prognosis of ACLF, reducing the risk of postoperative infection, progression from early ACLF to late ACLF, and further improving the 1-year post-transplant survival. The current priority for liver allocation based on MELD-Na can't give priority to liver donor matching to ACLF 1-2. Therefore, expanding the donor liver pool is an urgent need for early treatment of patients with ACLF. France team reviewed the development of APOLT to RAPID technology in liver transplantation for liver cirrhosis. Among them, 9 cases underwent two-step hepatectomy (including 5 cases of orthotopic assisted liver transplantation and 4 cases of RAPID surgery), 8 patients survived until the end of follow-up. Based on the experience of clinical practice, our center proposes and designs a clinical study of sequential adult left lateral lobe liver transplantation (SALT) for the treatment of early ACLF (Grade 1 and 2). On the basis of APOLT and RAPID, the safety and efficacy of sequential adult left lateral lobe liver transplantation were evaluated for the above patients.

Various neurotransmitters may share in the pathogenesis of hepatic and renal itching. Skin microbiota may share in the pathogenesis of pruritus.

Surgical procedures to remove a significant portion of the liver are used to treat various diseases including cancer. They have demonstrated to be the most effective treatment for selected patients. These procedures rely on the fascinating ability of the liver to grow back, allowing surgeons to remove of up to 70% of the organ in a safe manner. However, there are instances where severe complications and death occur due to the inability of the residual liver to perform all functions. It is estimated that up to 32% of patients undergoing this type of surgery will experience such complications. To prevent this, physicians calculate the total liver volume before surgery using radiology and estimate how much liver will remain after surgery. Only when the liver remnant is 30% or higher, the procedure is deemed safe. One of the main limitations of this strategy is that the estimated percentage of the liver remnant does not entirely reflect a proportional function. To overcome this limitation and avoid serious complications, a more precise assessment is required. Recently, a new scan was introduced using mebrofenin, which is metabolized in the liver and can be traced in a particular region of the organ using computer software. As a result, we can know with certainty, the percentual function of a portion of the liver, and if that portion will be sufficient to avoid complications and death after a major liver operation. This project proposes incorporating this technology for preoperative evaluation against our traditional assessment using just volume calculations. Participants will be randomly assigned to the traditional volume calculation or the new scan with mebrofenin, and we will compare how well both methods are able to predict complications and death after surgery. We are particularly interested in demonstrating if major complications and death after surgery are less using the new mebrofenin scan. Our study evaluating the introduction of a new and relatively harmful technique will help to better identify those patients with high risk for complications and death after a major surgical procedure on the liver. This will help in better selecting future patients and will allow for a more precise discussion during initial evaluation.

All patients having received at least one infusion of the Investigational Medicinal Product (IMP) HepaStem HHALPC during a previous interventional clinical study conducted by Promethera Biosciences