Pharmacogenetics Sampling of the CC-90007-CP-003 Study Cohort
Hepatic InsufficiencyThis is a multi-center observational follow-up study to collect saliva samples that allow pharmacogenetic analysis of the subjects that participated in the CC-90007-CP-003 study. Approximately 28 subjects with moderate and severe hepatic impairment and healthy control subjects with normal hepatic function will be enrolled.
Perioperative Lactate Kinetics in Patient Undergoing Major Liver Surgery
Liver FailureAcuteMajor liver surgery is associated with increased incidence of perioperative complications and increased mortality if these are not addressed quickly in a high dependency intensive care unit. Of these, posthepatectomy liver failure (PHLF) represents one of the most important cause of postoperative unfavourable outcome. The present study investigates the correlation between lactate levels and PHLF. Lactate levels were collected at six specific timepoints: preoperative, pre-dissection phase, post-dissection phase, end of surgery and 24-hours and 48-hours in the postoperative period.
A Pharmacokinetic Study of Baricitinib in Participants With Liver Disease
Liver DiseasesHepatic InsufficiencyThe main purpose of this study is to measure how much of the study drug called baricitinib gets into the blood stream and how long it takes the body to get rid of it. Healthy participants and those with liver disease may enroll. The study will last about 7 days for each participant, not including screening.
Microcirculation and Oxidative Stress in Critical Ill Patients in Surgical Intensive Care Unit
SepsisARDS3 moreAs medicine advances, many lives can be saved in the intensive care unit. However, when multiple organ failure occurs, the mortality rate of patients increases dramatically. Therefore, the major goal in the intensive care unit is to prevent the occurrence of multiple organ failure. The sepsis protocol and early goal directed treatment have great effects to reduce development of multiple organ failure and to decrease the mortality rate. However, sometime the condition of patient deteriorated in spite of both the mean blood pressure and mixed venous oxygen saturation are normal. Some experts recognize that there might be microcirculatory dysfunction of tissue or organ. The dysfunction of microcirculation might due to vasoconstriction or microthrombosis. Vasoconstriction might result from systemic inflammation, reactive oxygen species, or dysfunction of synthesis of NO (nitric oxide). Microthrombosis might result from systemic inflammation, reactive oxygen species, imbalance of coagulatory system, or damage of endothelial cell. In clinical practice, the oxidative stress is related to circulatory shock, sepsis, acute lung injury, and acute respiratory distress syndrome. This study tries to investigate the relation between oxidative stress and microcirculation. Furthermore, the investigators will try to investigate the correlation between the severity of oxidative stress and microcirculatory dysfunction and the severity of disease and prognosis. The investigators hope this study will help them to figure out the picture of disease progression of patients. It may conduct further study to modulate the oxidative stress, to improve the microcirculatory function, and finally to improve the outcome of patients.
A Multi-Center Trial to Study Acute Liver Failure in Adults
Acute Liver FailureFulminant Hepatic Failure1 moreThe purpose of this study is to collect clinical and epidemiological data as well as serum, plasma, urine, tissue and DNA samples on individuals who have acute liver failure and on individuals who have acute liver injury, a less severe group of patients who have coagulopathy but do not reach the threshold of encephalopathy.
Evaluating the Association Between Sphingolipid Metabolites and Post-hepatectomy Liver Failure
Post-hepatectomy Liver FailureHepatectomy is an essential treatment for various benign and malignant diseases of the liver. However, post-hepatectomy liver failure (PHLF) is still a life-threatening complication after hepatectomy. The pathophysiological mechanism of PHLF has not yet been fully elucidated, and there is still a lack of effective strategies for either prevention or therapy of PHLF. Sphingolipids include ceramides (CER), sphingomyelins (SM), glycosphingolipids (GSL), sphingosine (SPH), and sphingosine-1-phosphate (S1P) are multi-functional lipids that regulates cell proliferation, cell survival, cell death, inflammation, tissue fibrosis, cancer cell metastasis, and invasion. Liver is a main organ for metabolizing sphingolipids, dysregulation of specific sphingolipids is associated with several liver diseases, therefore sphingolipids have been proposed to be biomarkers of liver diseases, including hepatitis, liver cancer, fatty liver diseases, and liver fibrosis. Moreover, several studies have shown CER, SPH and S1P are critical in regulating pathophysiology of liver diseases, including liver regeneration, necrosis, and inflammation. Given that PHLF causes dramatic dysregulation in biochemical metabolism in liver, the investigators hypothesize that dysregulation of sphingolipid metabolism may also occur in PHLF, and the dysregulation of specific sphingolipids may serve as a biomarker or regulator during progression and recovery of PHLF. This project will examine the association between sphingolipid metabolism and PHLF. Levels of sphingolipid metabolites and their related enzymes in plasma and liver tissue of patients with hepatic resection will be measured by using liquid chromatograph/electrospray ionization/mass spectrometry (LC-ESI-MS/MS) and high-throughput real-time quantitative PCR. This project will facilitate us to identify specific sphingolipid metabolites as biomarker and regulator of PHLF.
A Validation Cohort for ACLF Diagnosis and Prognosis
Liver FailureAcute on Chronic1 moreAcute on chronic liver failure (ACLF) is a distinct entity encompassing the acute deterioration of liver function, culminating in multiple organs failure and high short-term mortality. Definitions and descriptions of ACLF vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are the main etiologies, respectively. To determine whether there are unified diagnostic criteria, severity classification and prognostic model for different etiologies of ACLF. Investigators had launched a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European CANONIC (Chronic liver failure-ACLF in Cirrhosis) study in China,the Ch-CANONIC study(NCT02457637). From Jan 2015 to Dec 2016, 2,600 inpatients with chronic liver disease complicated with ALI and/or AD were recruited. Data were collected during a 28-day hospitalization and continuous follow-ups were performed once a month until 36 months after hospitalization (at least 18 months up to now). Of these patients, 71.5% had HBV-related disease, 1833 had cirrhotic disease, and 767 had non-cirrhotic disease diagnosed by CT scan. Due to the lack of pathological gold standards, the diagnosis of ACLF is based on the clinical assessment of short-term mortality from organ functional parameters. In subsequent statistics and data analysis, investigators focused on (but not limit in) the relationship between short-term mortality and 6 parameters (bilirubin, INR, Creatinine, SpO2/FiO2, mean arterial pressure and West-Haven grade) from CLIF-C OFs (Chronic liver failure-Consortium Organ Failure score). And then a specific mathematical model has been constructed to obtain the available organ failure cutoff values. Subsequently, investigators carried out a diagnostical criteria for ACLF based on the results obtained from the model and get a good internal-validation result through risk ratio. Meanwhile, investigators conducted a precise prediction model for patients' prognosis and achieved a good predictive effect with consistency by AUC internal-validation. In addition, investigators summarized the course and some characteristics of ACLF. Therefore, investigators hope to launch another prospective multi-center cohort study with the same inclusion and exclusion criteria, and continue to recruit 800 to 900 patients (about 30% of the previous cohort) as the external validation cohort for the preliminary results mentioned above.
Exploring Biomarkers Predicting the Outcome of Acute-on-chronic Liver Failure
Acute-On-Chronic Liver FailureCirrhosis and Chronic Liver DiseaseAcute-on-chronic liver failure (ACLF) is an ailment with high incidence of multiorgan failure (MOF) and consequent mortality. Systemic inflammation and susceptibility to infection are characteristic pathophysiological features. Prostaglandin E2 (PGE2) could subdue systemic inflammation and alleviate liver injury in mice model. However, there are no studies evaluating PGE2 as a predictor of early mortality.This study is designed to investigate whether plasma PGE2 and its receptors are associated with development of MOF and predict short-term mortality in patients with acute-on-chronic liver failure. By the way, we will also measure several other potential predictive factors (C-reactive protein,severe hyponatremia, Second infections,Diabetes mellitus,High density lipoprotein,interleukin-10,serum bile acids,ferritin,the neutrophil to lymphocyte ratio,soluable urokinase plasminogen activator receptor,vWF-Ag levels and FVIII-to-PC ratios).
A Prospective Study of Application of Platelet Mapping in HBV-related Acute-on-chronic-liver Failure...
Thrombelastography,Acute on Chronic Liver FailurePlateletIneffective hemostasis or a paradoxical prothrombotic state of Acute-on-chronic liver disease (ACLF) has been well established. Thrombelastography measures the dynamics of thrombin production and provides a global assessment of coagulation incorporating the cumulative effect of the interactions at various levels between plasma components and cellular component of coagulation. And through the platelet mapping, it can help provide a picture of patients' function of platelet. This study aims to explore the predictive role of platelet mapping in ACLF prognosis, organ failure developments and short term mortality.
CytoSorb in Patients With Liver Failure
Liver DysfunctionHemoadsorption has been demonstrated to improve liver functional tests in patients with liver failure. The present study investigates the effects of three consecutive sessions of hemoadsorption, performed in accordance to the local protocol for treating patients with acute liver failure, on liver functional tests, severity scores and 30-days mortality. Paraclinical results and severity scores were obtained before and after the three consecutive sessions.