Active clinical trials for "End Stage Liver Disease"

End-stage liver disease (ESLD) refers to the late stage of liver disease caused by various chronic liver damage. ESLD is an important cause of global incidence rate and mortality, which has a significant impact on the health care system. ESLD is associated with various types of immune dysfunction. The artificial liver support system (ALSS) is an extracorporeal support system that temporarily and partially replaces the partial function of the liver. Its treatment mechanism is to remove all kinds of harmful substances, supplement essential substances, improve the internal environment, create conditions for hepatocyte regeneration and liver function recovery, or use it as a symptomatic support treatment method during the perioperative period of liver transplantation. In this study, we plan to use BS330 for plasma bilirubin adsorption. On this basis, we will add a CA280 cytokine adsorption column to establish a new artificial liver combination model CABA for the immune inflammatory damage mechanism of liver failure.

Globally, cirrhosis and liver cancer carries a huge burden and accounts for about 3.5% (2 million) of all deaths every year. Once decompensated, i.e. development of ascites, variceal bleed, encephalopathy, and jaundice, the life expectancy is markedly reduced to a median of two years. The definitive treatment in this stage, i.e., liver transplantation is limited by cost, lack of donors, and life-long immunosuppression. In addition to complications due to portal hypertension and hepatic insufficiency, decompensated cirrhosis is associated with malnutrition, sarcopenia, immune dysfunction, and impaired regeneration. Patients with cirrhosis are growth hormone (GH) resistant, with reduced insulin-like growth factor, which are linked to malnutrition and poor liver regeneration in cirrhosis. Diverse preclinical and clinical investigations in vitro and in vivo, have shown a benefit of GH in GH deficient, elderly and HIV positive patients. GH therapy in cirrhosis has been shown to improve nitrogen economy and to improve the GH resistance in a small pilot study by Donaghy et al. Also, GH therapy of short duration has shown to increase IGF1 levels, IGFBP-3 levels in patients of cirrhosis. GH therapy has also been shown to improve liver regeneration and protein synthesis after hepatectomy in patients of HCC with cirrhosis. However, there is a scarcity of data on clinical impact of long term administration of GH therapy in patients of cirrhosis. Hence, we undertook the present study to study the effect of growth hormone on clinical outcomes, malnutrition, immune cells and liver regeneration in patients with cirrhosis.

This is a Phase 3, multicenter, randomized, controlled, parallel-group, open-label study to evaluate the effects of plasma exchange using human serum albumin 5% (PE-A 5%) in acute-on-chronic liver failure (ACLF) subjects. The study will involve approximately 40 study centers in the United States, Canada, and Europe with expertise in the management of subjects with ACLF. Subjects with ACLF at a high risk of hospital mortality will be enrolled. The study will consist of a Screening Period during which subjects will be randomized (1:1) to receive either standard medical treatment (SMT) + PE-A 5% (treatment group) or SMT only (control group), followed by a Treatment Period, and a Follow-up Period. The Treatment Period for subjects in the SMT+ PE-A 5% treatment group will be between 7 and 17 days, depending on ACLF evolution. The Treatment Period for subjects in the SMT control group will be a minimum of 7 days for all subjects and up to 17 days depending on the ACLF evolution. Subjects in this group will receive SMT according to the institution's standards. The Follow-up Period for subjects in both groups will be 90 days.

Early treatment of invasive fungal infections (IFI) may prevent undue mortality in acute on chronic liver failure (ACLF) patients. We aim to study the impact of early empiric treatment (based on clinical suspicion) of IFI as compared to pre-emptive treatment (based on biomarkers and culture positivity) on the outcomes in ACLF patients with suspected IFI in a randomized trial. The ACLF patients with clinically suspected IFI would be randomly allocated to empiric treatment or pre-emptive treatment group and followed up clinically to assess the impact on survival, clinical outcomes and cost-effectiveness and safety of such an approach. The protocol is designed to cut- down unnecessary usage and to curtail the duration of antifungals use in ICUs based on biomarkers/culture-driven stoppage rules. The results will fuel further studies on formal cost-effective analysis and antimicrobial stewardship protocols in ACLF patients.

Acute on-chronic liver failure (ACLF) is a severe liver disease with a 28-day mortality rate of up to 40%. When the patients get 3 or more organ failures, the 28-day mortality rate is up to 82.6%. Though the ACLF patients have high short-term mortality, and the only effective treatment method is liver transplantation. However, few patients can be treated due to the scarcity of liver source, rapid disease progression and short transplantation window. Our team evaluated the platelet function of 100 patients with ACLF by using the thromboelastograghy (TEG 5000). It was found for the first time that the reactivity of platelets of ACLF patients decreased, and the platelet inhibition rate (especially the ADP pathway) was related to patients'short-term prognosis. When the ADP inhibition rate was 70%, the patients'28-day mortality was up to 100%. However, the mechanism of low platelet response to ADP in ACLF patients is still unclear. We found that the platelet function in patients with ACLF 2-3 grade and inhibition rate beyond 70% was improved and the 28-day mortality decreased after platelet transfusion. Whether platelet transfusion can prolong survival time needs to be determined in a prospective controlled study. Therefore, this study is expected to find a new therapeutic method to reduce the mortality of patients with ACLF.

This Phase 2a clinical trial is a dose escalation study of the safety, tolerability, and efficacy of hepatocyte transplantation into lymph nodes via endoscopic ultrasound among subjects with end-stage liver disease.

Acute liver failure patients posed high mortality rate despite receiving standard therapy. The severity and mortality even higher in patients with underlying liver disease. Acute liver failure cause hyperinflammatory response in early stage and immunoparalysis in later stage. The surge of proinflammatory cytokines leads to multiorgan failure and more liver injury. Subsequent immunoparalysis may lead to lethal secondary infections. Liver support system had been used in acute and acute ontop chronic liver disease for last several decades. Double plasma molecular adsorption system (DPMAS) is one of the promising non-biological liver support system that have been extensively investigated in acute ontop chronic liver failure from hepatits B viral. DPMAS circuit consist of BS330 (bilirubin adsorber) and HA330 (Cytokines adsorber). Thus, DPMAS can also remove various cytokines. The effect of DPMAS on immune function in these patients has not been explored. Recent randomized controlled trial by Srisawat et al. demonstrated improvement of mHLA-DR in septic shock patients who received polymyxin B extracorporeal therapy compare to control arm. Since liver failure show change of immunological profile resemble to sepsis. Investigators proposed that removal of toxic liver toxins and lethal cytokines by DPMAS will improve immunological profiles in acute ontop chronic liver failure patients. Investigators plan to conduct a randomized controlled trial in acute ontop chronic liver failure patients who admitted to intensive care unit. Investigators plan to compare the immunomodulatory effects of DPMAS with standard treatments.

Iron deficiency and altered homeostasis due to inflammation and decreased iron utilization are main factors involved in anemia in liver disease. Lactoferrin is a first line defence protein for protection against microbial infections and subsequent development of systemic disease as seen with systemic inflammatory response syndrome (SIRS) and sepsis. Lactoferrin with iron has been shown to be efficacious with anemia in chronic disease, in pregnancy and in cancer patients with fewer side effects than oral iron alone. High exposure to iron is associated with increased inflammation which is associated with worse cardiovascular outcomes. Lactoferrin can help reduce the total iron dose and hepatic inflammation.

A Phase 2, multi-center, randomized, controlled, open-label study to evaluate the effects of the intraperitoneal, liposomal formulation VS-01 in patients with an acute episode of hepatic and/or extrahepatic organ dysfunctions and failures in the presence of liver cirrhosis (Acute-on-Chronic Liver Failure, ACLF) and accumulation of fluid in the abdominal cavity (ascites)

Patients with cirrhosis patients have a high incidence of sepsis which can trigger decompensation and may result in prolonged hospital stay and increased mortality. About 30%-50% admissions of patients with cirrhosis have sepsis at presentation and about 15% patients admitted to hospital develop sepsis during the hospital stay . After infection develops, the patient may develop acute kidney injury (AKI), shock, encephalopathy or disseminated intravascular coagulation (DIC) further decreasing the chances of survival. In fact, sepsis in patients with cirrhosis is associated with 15% in-hospital mortality, approximately double that of patients without sepsis. So, sepsis is directly responsible for 30-50% of deaths in cirrhosis . Therefore, it is critical to manage sepsis early and appropriately in cirrhosis to reduce the complications and mortality. Early administration of fluids, source control and empirical antibiotics along with vasopressors if refractory shock are essential components of treatment in all patients with sepsis. Currently, the most accepted strategy for early sepsis management is a combination of early goal directed therapy (EGDT) and physiological parameters, such as urine output, lactate clearance, and administration of antibiotics, within 1 hour of presentation . The use of central venous pressure assessment is fallacious for gauging adequacy of fluid resuscitation in cirrhosis, and the difficulty of performing echocardiographic assessments in the setting of ascites and cirrhotic cardiomyopathy is also well described .