De Novo Lipogenesis in Severity of NAFLD
Nonalcoholic Fatty Liver DiseaseNonalcoholic Steatohepatitis3 moreNAFLD is the most prevalent liver disease in the U.S., and there is a serious need to understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH). Previous studies has shown that elevated de novo lipogenesis (DNL) is the unique, early event distinguishing patients with NAFLD from equally-obese subjects with low IHTG. The purpose of this study is to directly by measure DNL in human liver tissue and comparing it to liver histological scores from patient biopsies.
Metagenomic Next-Generation Sequencing for Diagnosis of Ascites Infection in End-stage Liver Diseases...
Ascites InfectionAscites is the most common complication of cirrhosis, and its development is associated with substantially increased mortality. Ascites infection including spontaneous bacterial peritonitis (SBP), bacterascites and fungal infections. SBP is one of the most feared complications of ascites. The EASL guidelines recommend that diagnostic criteria of SBP is defined on the ascitic fluid polymorphonuclear leucocytes (PMN) count ≥250 cell/μl, with or without ascites fluid positive culture. However, in clinical practice. Up to 30% of hospitalized patients are considered as suspicious SBP, and treated as SBP without a laboratory-confirmed cause of infection. and is present in 10-30% of all hospitalized patients with ascites. Besides, fungal infection in ascites was aslo related to high mortality in cirrhosis patients. Thus, to diagnose ascites infection promptly is the key step to prevent the complication. Since, the sensitivity of bacterial culture is limited even if ascites is directly injected into blood culture bottles at the besides. New method to identified the pathogen is needed. Here, we aim to use metagenomic next-generation sequencing(mNGS) to provide the first-ever demonstration of precision medicine for the diagnosis of ascites infection in hospitalized patients, with immediate impact on clinical care and patients outcomes. The method of mNGS is undertaken by BGI Genomics Company which is a licensed clinical diagnostic laboratory in China. In this multicenter and prospective clinical study, we are planning to detect ascites sample by mNGS and compare the performance of mNGS and routine microbiological testing. Ultimately, we aim to improve the diagnosis of ascites infection and improve patients' outcomes.
Biomarkers of Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis Following...
NASH - Nonalcoholic Steatohepatitis; NAFLD - Nonalcoholic Fatty Liver DiseaseThe purpose of this study is to evaluate imaging and other biomarkers of non-alcoholic fatty liver disease before and after bariatric surgery.
Serum Selenium and Zinc Levels in Non-alcoholic Fatty Liver Disease Patients
NAFLDNon-alcoholic fatty liver disease (NAFLD) includes a wide range of disorders that consist of simple fatty infiltration, steatohepatitis (NASH), and end-stage liver disease (cirrhosis). NAFLD is the most common cause of chronic liver disease worldwide and increases the risk of end-stage liver disease and hepatocellular carcinoma (HCC) . While risk factors such as obesity, diabetes, and a sedentary lifestyle may increase the risk of NAFLD, studies have shown that environmental exposures may further contribute to the pathogenesis of NAFLD. Although the pathogenic role of macronutrients is well established in both NAFLD and obesity, the contribution of micronutrients to NAFLD pathogenesis has garnered less attention than with obesity. Selenium is an essential element in many biological functions and is an important component of human nutrition. Exposure to selenium can be found in nature, such as rocks and sediment, air, soil, fuel oil, drinking water and nutritional supplementation. It is a major component of many enzymes such as glutathione peroxidase and plays an important role in anti-oxidation, DNA synthesis, reproduction, muscle function, and thyroid metabolism. Selenium concentrations have been studied in many diseases and organ systems including the liver. However, the exact relationship between selenium in patients with NAFLD is unclear. Selenium is an essential element in many biological functions and is an important component of human nutrition. It is a major component of many enzymes such as glutathione peroxidase and plays an important role in anti-oxidation, DNA synthesis, reproduction, muscle function, and thyroid metabolism. Selenium concentrations have been studied in many diseases and organ systems including the liver. However, the exact relationship between selenium in patients with NAFLD is unclear. Despite data suggesting mineral deficiencies in NAFLD patients, most data do not support insufficient mineral consumption as a possible mechanism for these deficiencies, except in the case of zinc deficiency. Zinc is the second most prevalent trace element in the body. It is integrally involved in the normal life cycle and has many important regulatory, catalytic, and defensive functions. Zinc deficiency occurs in many types of liver disease, especially more advanced/decompensated disease.
The Effect of Lifestyle-induced Hepatic Steatosis on Glucagon-stimulated Amino Acid Turnover
Non-Alcoholic Fatty Liver DiseaseGlucagon ResistanceMany patients with type 2 diabetes exhibit elevated plasma concentrations of the glucose-mobilising pancreatic hormone glucagon; i.e. hyperglucagonaemia. This contributes to the hyperglycaemic state of the patients and is considered an important component in the pathophysiology of type 2 diabetes; but the mechanisms underlying this phenomenon remain unclear. The liver constitutes the main target organ of glucagon, and studies have shown that hyperglucagonaemia goes hand in hand with hyperaminoacidaemia and that both are associated with non-alcoholic fatty liver disease (NAFLD), independently of the presence of type 2 diabetes. In line with this, several recent studies support the existence of a feedback-cycle between the liver and the pancreatic alpha cells, governed by circulating glucagon and amino acids. The investigators hypothesise that the presence of hepatic steatosis results in hepatic glucagon resistance at the level of amino acid turnover, i.e. impaired glucagon-induced suppression of circulating amino acid concentrations. If this hypothesis proves correct, it would establish build-up of fat in the liver as a core mechanism underlying hyperglucagonaemia and, since the hyperglucagonemia is at least partly responsible for the fasting hyperglycaemia, as an important contributor to the hyperglycaemia of type 2 diabetes.
Liver and Splenic Stiffness in Predicting Esophageal Varices Needing Treatment in NASH Related Compensated...
Chronic Liver DiseasePatients with chronic liver disease (CLD) are at risk of developing clinically significant portal hypertension (CSPH). In the Baveno VI consensus a new term "compensated advanced chronic liver disease (cACLD)'' has been proposed to better reflect that the spectrum of severe fibrosis and cirrhosis is a continuum in asymptomatic patients. Liver stiffness by TE is sufficient to suspect cACLD in asymptomatic subjects with known causes of CLD. TE values <10 kPa in the absence of other known clinical signs rule out cACLD; values between 10 and 15 kPa are suggestive of cACLD but need further test for confirmation; values >15 kPa are highly suggestive of cACLD. Patients with a liver stiffness <20 kPa and with a platelet count >150,000 have a < 5 % risk of having varices requiring treatment, and can avoid screening endoscopy. SSM can also predict the presence of CSPH and varices requiring treatment. Some studies have shown superiority of splenic stiffness over liver stiffness in predicting varices requiring treatment likely attributable to the better performance of SSM compared with LSM in more severe portal hypertension because it reflects better the hemodynamic component of portal hypertension. However, there are few studies on NAFLD and most are on viral hepatitis related cACLD. Moreover, very few studies are published on splenic stiffness from Indian subcontinent. Similarly baseline HVPG is an important predictor of disease progression patients of NAFLD related cACLD, but requires invasive hepatic vein catheterization. Hence, we intend to do the study assessing diagnostic utility of splenic and liver stiffness in predicting varices needing treatment in NAFLD related cACLD and compare from other noninvasive markers and its correlation with HVPG.
Intraoperative Hemodynamic Management and Postoperative Outcomes in Liver Transplantation
Liver FailureLiver Diseases4 moreThe overarching objective of the research program entitled ELIPTO (Enhancing Liver Insufficiency and Postoperative Transplantation Outcomes) (www.elipto.ca) is to improve the perioperative care of liver transplant recipients. One of this program's purposes is to better define the effects of intraoperative hemodynamic management on postoperative outcomes in adult liver transplant recipients. In this study, the incidence of postoperative complications within this population will be defined in Canada and France and the association between intraoperative hemodynamics and postoperative outcomes will be measured. Liver transplantation improves the survival of patients with end-stage liver disease (ESLD). It is the second most transplanted organ with a continuously increasing annual number of transplantations, an observation partly explained by an endemic ESLD etiology in the United States, the obesity-related non-alcoholic steatohepatitis (NASH) cirrhosis. In recent decades, although sicker patients are prioritized, survival has improved possibly through an overall improvement in the quality of care. However, postoperative complications have concomitantly increased. On average, liver transplant recipients suffer from more than three postoperative complications, mainly infectious, pulmonary, renal or graft-related, two thirds of them being severe. In a low-risk patients cohort, close to 60% of all patients suffered from at least one severe complication up to 6 months after surgery. Such complications increase mortality, readmissions and cost of care. Organs available for transplantation are a scarce resource; up to 10% of grafts are no longer functional after one year. Interventions that improve patients' postoperative and graft outcomes are needed and few perioperative ones are supported by high-quality evidence.
Lenvatinib Combined Anti-PD1 Antibody for the Advanced Hepatocellular Carcinoma
Hepatocellular CarcinomaAnti-PD1 Antibody1 moreFor the advanced hepatocellular carcinoma (HCC), the targeted therapy and immunotherapy are recommended. This study focused on the management of Lenvatinib combined anti-PD1 antibody for the HCC. This study will create a database that will provide clinical parameters and outcomes of patients undergoing Lenvatinib and anti-PD1 antibody as part of their standard of care in hopes of answering key clinical questions.
Exercise Intervention in Liver Transplant Candidates
Liver DiseasesThe aim of the study is to investigate the effect of personalised exercise interventions in liver transplant candidates, aiming to prevent or limit sarcopenia and frailty, as well as improving their cardiorespiratory health.
COVID19-FOIE National Observatory
Liver DiseasesCOVID19Background: The COVID19 and liver relationships are very rare. The preliminary Chinese data indicate that 2-11% of patients treated for COVID19 had an underlying chronic liver disease. However, there is no clinical data on morbi-mortality in this context. Objectives: Primary Objective: Evaluate the mortality related to Covid-19 in patients with a chronic liver disease Secondary objectives: Evaluate the mortality (liver-related and no liver-related) due to the Covid-19 according to the cirrhotic status, an history of hepatocellular carcinoma, an immunosuppressive treatment and its type, the etiology-ies of liver disease at the diagnosis of Covid-19 (viral hepatitis -B and/or C-, liver disease related to alcohol consumption, metabolic syndrome, hemochromatosis, immune liver disease, other or unknown), and comorbidities Evaluate the liver morbidity related to Covid-19, including incidence of liver biochemical abnormalities in patients with normal liver enzymes values or of a 2-fold increase of usual values for AST, ALT, GGT, Alcalines Phosphatasis incidence of liver complications (acute hepatitis, liver insufficiency, decompensation of cirrhosis, encephalopathy, renal insufficiency) Patients: All patients with a liver disease (chronic or acute) with a positive diagnosis of Covid-19 assessed either by positive PCR or specific thoracic abnormalities at TDM Methodology: Observational ambispective study consisting exclusively of a collection of data from patients with liver diseases and managed for COVID 19 The data is collected and transcribed on a secure electronic eCRF hosted at the Assitance Publique des Hôpitaux de Paris and accessible online from the AFEF website Duration and organisation of the research: After information of the patients and making available a non-opposition form, the main demographic and clinical data related to the liver disease and to the COVID19 already collected in the patient's medical record will be collected in a dedicated e-CRF. Effective of the study: All consecutive patients included in the study whose data are collected e-CRF until 31/12/2020.