
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).

Vitamin D Replacement in Nonalcoholic Fatty Liver Disease
Nonalcoholic Fatty LiverVitamin D deficiency is very common in patients with fatty liver disease as evidenced by our observations in the Metabolic Liver Clinic and that reported by others. We also observed that patients with more severe fatty liver disease had lower Vitamin D concentrations. Others have shown that replacing Vitamin D in patients with cirrhosis is effective and even patients with Vitamin D replete status have lowering of Vitamin D over time if not supplemented. One of the measures of liver injury in NAFLD is the plasma concentration of ALT and we will use this to follow patients as is currently done as standard of care. All patients in the Metabolic Liver Clinic are being routinely screened for Vitamin D deficiency as standard of care and treatment is being started with oral supplementation, but there are not standardized protocols to determine success of therapy. We hypothesize that patients with NAFLD with low Vitamin D levels will respond appropriately to Vitamin D supplementation for 6 months.

SWE Liver Stiffness as a Predictor of Progression of Chronic Liver Diseases
Liver FibrosesThis study is a multicenter individual patient-based meta-analysis that will assess the performances of liver stiffness measurements performed with supersonic shear imaging shearwave elastography (SSI-SWE) in patients with liver fibrosis to predict progression of chronic liver disease.

Assessment of Renal Changes in Patients With Non Alcoholic Fatty Liver Disease
Non-Alcoholic Fatty Liver DiseaseChronic Kidney DiseasesAssess the renal changes in patients with non-alcoholic fatty liver (NAFLD).

Patient Understanding of LiverMultiScan
Liver DiseasesThis is a qualitative study to determine which factors affect the patient experience of having a liver MRI, what information patients would like to receive after their MRI, and how patients would like this information communicated to them.

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.

Gut Microbiota in Chronic Noncommunicable Diseases
Arterial HypertensionAtherosclerosis Occlusive Disease7 moreIt is an observational study in patients with chronic noncommunicable diseases (i.e. cardiovascular diseases, diabetes mellitus, non-alcoholic fatty liver disease, chronic obstructive pulmonary disease and asthma ) and control group with no signs of these conditions. The study has a prospective part planned for 2021 and a retrospective part which includes the patients enrolled between 2018-2020. The aim of the study is to investigate gut microbiota composition, its metabolites, levels of inflammatory and other markers of the disease in prospective groups (arterial hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma, non-alcoholic fatty liver disease and control patients) as well as in retrospective groups (chronic heart failure with preserved and reduced ejection fraction, obstructive atherosclerosis of any vascular bed, arterial hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma, non-alcoholic fatty liver disease, and control patients). Also we are planning to investigate the association between gut microbiota composition and its metabolites, levels of inflammatory and other markers of the disease in retrospective and prospective groups.

Cognitive Function of Alcoholic Compensated Liver Cirrhosis
Alcoholic Liver DiseaseDifferences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis

Hepatic and Cardiac Metabolic Flexibility in Subjects With T2DM With and Without NAFLD
NAFLD - Non-Alcoholic Fatty Liver DiseaseType 2 DiabetesNon-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiac steatosis. The mechanisms behind why some subjects progress from NAFLD to NASH and the link between cardiac involvement and NAFLD are poorly understood, but must include altered cardiac and intrahepatic lipid handling. Investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with type 2 diabetes with and without NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in type 2 diabetic subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using tracer techniques (11Cpalmitate PET tracers and triglyceride (TG) tracers) to study cardiac and liver substrate trafficking, as well as MR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism.