Clinical Research Directory

The Correlation Between hs CRP TG Triglycerides Glucose Index in NAFLD and Liver Fibrosis

The Correlation between hs CRP TG triglycerides Glucose index in NAFLD and liver fibrosis

LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Moderate or Advanced Liver Fibrosis

This study is open to adults who are at least 18 years old living with obesity and have: * a confirmed liver disease called non-alcoholic steatohepatitis (NASH)/metabolic associated steatohepatitis (MASH) and * moderate or advanced liver fibrosis People with a history of acute or chronic liver diseases other than MASH or chronic alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with MASH and moderate or advanced liver fibrosis improve their liver function. This study has 2 parts. The purpose of the first part of this study is to find out the effect of survodutide on MASH and liver fibrosis. The purpose of the second part is to find out how safe and effective survodutide is in improving liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. The survodutide doses are slowly increased until the target dose is reached. All participants receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 7 years. During this time, they regularly visit the study site or have remote visits by video call. For about the first year of the study, participants have these visits every 2 weeks, increasing to every 4 weeks and then every 6 weeks. After being in the study for a little over a year participants will then alternate between visiting the study site or having a remote visit every 3 months until the end of the study. The doctors check participants' health and take note of any unwanted effects. The participants' body weight and effects on the stomach and intestines are regularly measured. At some visits the liver is measured using different imaging methods. At 2 or 3 visits doctors take a small sample of liver tissue (biopsy). The participants also fill in questionnaires about their symptoms and quality of life. The results are compared between the groups to see whether the treatment works.

Prevalence and Risk Factors of Metabolic-Associated Hepatic Steatosis in Individuals Living With Type 1 Diabetes

The goal of this observational cross-sectional study is to assess the prevalence and stage of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), specifically liver steatosis and fibrosis in adults aged 18 and older living with type 1 diabetes or Latent Autoimmune Diabetes in Adults (LADA) in Quebec. The main questions it aims to answer are: 1. What is the prevalence and severity of liver steatosis and fibrosis among people living with type 1 diabetes in Québec? 2. Are there patients with type 1 diabetes who have advanced, undiagnosed stages of liver disease that require management but are missed by current standard care practices? Researchers will compare three participant subgroups based on adiposity (a control group without increased adiposity, an overweight group with increased adiposity, and an obesity group with increased adiposity) to see if the prevalence and severity of hepatic steatosis and fibrosis are highest in the obesity group and lowest in the control group. They will also explore if variables and potential risk factors associated with liver disease differ across these subgroups. Participants will attend a single study visit where they will be asked to: * Provide clinical data through laboratory analyses. * Undergo specific clinical procedures. * Complete validated questionnaires.

Rapid Breath-hold Quantitative Macromolecular Proton Fraction Imaging for Liver Fibrosis

Chronic liver disease is a major health problem worldwide. Liver fibrosis is a key feature in most chronic liver diseases. When identified early, liver fibrosis may be reversible. Currently, liver biopsy is the gold standard for the diagnosis of liver fibrosis. Liver biopsy; however, is invasive. Non-invasive diagnostic tools are increasingly used in clinical practice. However, the existing noninvasive methods still have significant limitations to detect early-stage liver fibrosis. Liver fibrosis is characterized by excessive deposition of collagen-rich connective tissues in the liver. The macromolecular proton fraction (MPF) is an MRI parameter which characterizes the magnetization transfer (MT) effect in tissues. Quantitative MPF imaging is non-invasive and can be used to measure collagen deposition in the liver due to the strong MT effect of collagen. It has been reported MPF quantification can be used for diagnosis of early-stage liver fibrosis. However, the existing approaches require B1, B0, and T1 map in addition to the imaging data for MPF quantification, which makes it challenging to adopt them for routine clinical use. The investigators propose a fast and robust MPF quantification approach. In contrast to the existing methods which rely on saturation radiofrequency pulses for MPF quantification, our approach is based on spin-lock radiofrequency pulses which have minimum Rabi oscillations. The whole imaging data can be acquired within a breath-hold less than 8 seconds. Our approach only needs a B1 map in addition to the imaging data for MPF quantification. The preliminary clinical studies on 3.0T MRI show the measurement using our approach is specific to collagen content and can be used to detect early-stage liver fibrosis. To further confirm the clinical value of the proposed approach, the investigators will investigate the relationship of the collagen content measured using the proposed non-invasive imaging approach and those measured based on morphometry analysis of histology, and determine the diagnostic value of the proposed method for detection of early stage liver fibrosis in a large cohort. The investigators will also perform comparative studies of the proposed method and the state-of-the-art quantitative MPF imaging technique. This project will provide a diagnostic technology for early detection of liver fibrosis. The proposed MRI technology also has potential to be used for other clinical purposes.

Incidence of Liver Disease-Related Outcomes in People With HIV

Antiretroviral therapy can effectively control the replication of HIV, prolong the lifespan of patients infected with HIV, and improve their quality of life.At the same time, non-AIDS-related diseases such as diabetes and chronic liver diseases are increasing day by day.Metabolic associated fatty liver disease (MAFLD) is a chronic progressive liver disease caused by overnutrition and insulin resistance in genetically susceptible individuals. It was formerly known as non-alcoholic fatty liver disease (NAFLD).With the continuous improvement of living standards and the constant change of lifestyles, the incidence of metabolic associated fatty liver disease is gradually increasing. Metabolic associated steatohepatitis (MASH) may further develop into liver cirrhosis, liver failure and hepatocellular carcinoma, and is the third most common cause of liver transplantation. In HIV patients, early identification of significant liver fibrosis and MASH with fibrosis is of vital importance.However, due to the fact that the pathogenesis of liver fibrosis in HIV patients is more complex than that in the general population, it involves multiple factors such as the virus, reverse transcriptase drugs, chronic inflammation, and immune disorders.However, the current clinical research on metabolic-related fatty liver fibrosis in people with HIV is still rather limited.

City-Hospital Collaboration for Early Detection of Liver Fibrosis in Primary Care: A Secondary Prevention Project in the Grenoble Health Area

Cirrhosis and hepatocellular carcinoma (HCC) are responsible for 25,000 deaths per year in France. The main causes are excessive alcohol consumption, metabolic steatosis, and hepatitis B and C. Fibrosis, classified from F0 (absence of fibrosis) to F4 (cirrhosis), is the sole determinant of liver-related mortality, particularly from stage F3. The incidence of metabolic steatosis is increasing, associated with a rise in mortality from chronic liver diseases (CLD). CLDs, often asymptomatic, are diagnosed late, reducing patient survival. Recommendations exist for the screening of hepatic fibrosis in at-risk patients (alcohol, diabetes, metabolic syndrome). This screening relies on calculating the FIB-4 score (calculated from widely prescribed variables: AST, ALT, platelets, age), followed by Fibroscan® (a non-invasive test for hepatic fibrosis) if FIB-4 \> 1.3. A Fibroscan® result \<8kPa excludes advanced fibrosis, while a result \>9.6kPa suggests advanced fibrosis and ≥15kPa indicates cirrhosis. The appropriate care pathway includes a risk reduction program, a specialized consultation for patients with Fibroscan® ≥8kPa, and semi-annual screening for HCC in the case of cirrhosis. Indeed, it has been shown in a French cohort of patients with viral C cirrhosis that adherence to semi-annual screening is associated with better survival. Eligible patients are primarily seen in primary care, and INCA has published a recommendation intended for general practitioners to improve the screening of fibrosis \[13\]. However, FIB-4 is poorly known among general practitioners \[14\], and access to Fibroscan® remains limited \[15\], hindering the implementation of the recommendations. Therefore, a care pathway has been established in the Grenoble area, initiated by Professor Costentin, allowing access to Fibroscan® for patients in primary care, starting from 2022 at the CHU. The objective is to evaluate the completion of the pathway, particularly the management of MCF risk factors and referral to specialized consultation for patients with Fibroscan® ≥8 kPa.

MR Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B

How to construct a non-invasive, accurate, and convenient method to evaluate the severity of liver fibrosis (LF) is an important general problem in the management of patients with chronic hepatitis B (CHB). We plan to investigate the ability of magnetic resonance elastography (MRE) to grade fibrosis in chronic hepatitis B and apply to clinical longitudinal follow-up.

The Phase 1, Open-label, PET Trial Designed to Investigate the Effect of AZD2389 on FAP Occupancy in the Liver in Participants With Advanced Liver Fibrosis.

This is a phase 1, open-label, PET trial. The study is designed to investigate the effect of AZD2389 on FAP occupancy in the liver in participants with advanced liver fibrosis.

Thyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans

Nonalcoholic steatohepatitis (NASH) is the aggressive form of nonalcoholic fatty liver disease, which is rapidly becoming a worldwide public health problem. It is more common in the military and Veteran population compared to the general US population. NASH may progress to end-stage liver disease and primary liver cancer, and hence there is critical need for effective treatment. The goal of this clinical trial is to test whether low dose thyroid hormone administered to Veterans diagnosed with NASH can be an effective therapy mediated by improvement in breaking down fat in the mitochondria. The study will be conducted in two stages, the first stage is for proof of concept to be followed by interim analysis. If the interim analysis supports the merit for continuing the study, the clinical trial will proceed to stage 2 for continuation. This study will provide new information and strategies for treatment of NASH using low dose thyroid hormone that will be highly relevant and impactful to the health of the Veteran population.

A Phase IIIc Clinical Study to Evaluate the Long-term Treatment of Hydronidone Capsules for Liver Fibrosis in Patients With Chronic Hepatitis B.

This study is conducted as a randomized, double-blind, placebo-controlled, multicenter clinical trial on a background of entecavir therapy. It aims to evaluate the clinical benefits of Hydronidone Capsules in patients with liver fibrosis due to chronic hepatitis B. The study consists of a Screening/Baseline Period (4 weeks) and a Dosing/Observation Period (planned duration of 5 years, including a 52-week primary treatment phase and a 208-week long-term treatment phase).

Study of Hydroxynidone Capsules in Patients With Hepatic Impairment and Matched Healthy Controls

This trial adopts a single-center, single-dose, open-label, non-randomized, parallel-controlled design. It will be conducted in participants with varying degrees of hepatic impairment, as well as in participants with normal hepatic function matched for sex, age, and BMI. The administration method is a single oral dose of 90 mg hydroxynidone capsules under fasting conditions. Participants meeting the inclusion criteria with corresponding degrees of hepatic impairment and those with normal hepatic function will be enrolled. Each group will complete the study with 10 participants. Matched participants will be comparable in terms of sex (±1 participant per sex), mean age (±10 years), and mean BMI (±10%).

Non-invasive Assessment of Liver Fibrosis in a French Cohort of Pediatric Patients With Type III Glycogen Storage Disease: Current State and Perspectives

Patients with type III glycogen storage disease (GSDIII) can develop liver fibrosis, which can be complicated by liver failure or even hepatocellular carcinoma. Since the beginning of the 21st century, non-invasive techniques for assessing fibrosis, such as liver elastography, have been developed. These techniques often make it possible to avoid liver biopsies during patient follow-up and have already been validated in the management of several diseases in adults. These techniques are also beginning to be recommended for monitoring certain chronic liver diseases in children.

Effect of Mediterranean Diet Combined With Intermittent Fasting on Liver Fibrosis Compared to Naltrexone/Bupropion in People With Cardiometabolic Risk Factors (MEDFAST-study)

In the Netherlands, there are many people with cardiometabolic diseases. More than half of these people also have fatty liver. This is a build-up of fat in the liver (steatosis) and can lead to long-term scarring (fibrosis) and even death of the liver. Losing weight can help reduce this. Losing weight can be done with medication such as naltrexone/bupropion (Mysimba®), which is often prescribed to people with cardiometabolic diseases, but losing weight can also be done with diet. In this study, the investigators want to combine a Mediterranean diet (with lots of vegetables, fruits, whole grain products, nuts and olive oil) with intermittent fasting. In addition participants are not allowed to eat after the evening meal. The investigators will compare this with a group of participants receiving Mysimba®, to see if a diet with intermittent fasting might be better for reducing liver steatosis and fibrosis in people with cardiometabolic diseases.

Research on the Protective Effects of Phycocyanin Against Liver Fibrosis and Cirrhosis

This clinical trial aims to determine whether phycocyanin, a natural protein derived from spirulina, can help treat liver fibrosis or cirrhosis in adult patients. The main questions it aims to answer are: * Can phycocyanin reduce blood levels of liver enzymes (such as ALT and AST) that indicate liver damage? * Can phycocyanin improve liver stiffness as measured by ultrasound? Researchers will compare the phycocyanin intervention group with a control group that receives a placebo (a similar-looking maltodextrin supplement without active ingredients) to explore if phycocyanin is more effective in treating liver fibrosis/cirrhosis. Participants will: * Take one sachet of either phycocyanin or placebo daily for at least 4 weeks. * Attend regular clinic appointments (typically every 2-3 months) for routine monitoring of your liver condition, which will include blood and urine tests. * Provide blood and stool samples once before the treatment and once after the 4-week treatment period. * Undergo an ultrasound evaluation of liver stiffness. The study will last approximately 2 years, and the personal information of all patients will be kept strictly confidential.

Single-cell Multiomics and Spatiotemporal Omics Analyze the Mechanism of Liver Degenerative Disease

The purpose of this observational study is to employ single-cell multi-omics and spatial omics technologies to characterize the spatial and immune structures within the livers of patients with fatty liver, hepatic hemangioma, focal nodular hyperplasia, liver fibrosis, cirrhosis, and HBV infection. The primary questions it aims to address are: Investigate the mechanisms of liver degenerative changes during the processes of liver aging, fatty liver, HBV infection, liver fibrosis, and cirrhosis. Characterize the molecular features and cellular networks at different stages of liver degeneration and identify new targets and mechanisms for the cure of the aforementioned diseases. The study will collect peripheral blood and discarded liver tissue from patients with hepatic hemangioma, fatty liver, HBV infection, liver fibrosis, and cirrhosis who are undergoing hepatectomy or liver biopsy.

The Phase Ⅰd Clinical Trial of Hydronidone Capsules

Based on the Phase I (Ia, Ib, Ic) clinical pharmacokinetic study of Hydronidone Capsules, a clinical pharmacokinetic trial of Hydronidone Capsules (specification: 30 mg/capsule) was conducted, including single-dose administration, multiple-dose administration, and a food-effect study. The aim was to investigate the safety, tolerability, and pharmacokinetic characteristics of higher doses of Hydronidone Capsules (specification: 30 mg/capsule) in healthy subjects, in preparation for future expansion of indications.

Effect of Endoscopic Sleeve Gastroplasty in Patients With Obesity and MASH: A Randomized Controlled Trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

Is There a Relationship Between Uric Acid Level and Liver Fibrosis in Obese Patients

1. Identifying the association between hyperuricemia and NAFLD can lead to early detection and prevention of liver fibrosis in adult obese patients. 2. Understanding the relationship between hyperuricemia and NAFLD can inform targeted therapy, such as urate-lowering treatment, to potentially slow disease progression. 3 - To examine the relationship between serum uric acid levels and liver fibrosis severity\*: Assessing the correlation between serum uric acid levels and the severity of liver fibrosis in adult obese patients with NAFLD. 4- To identify potential mechanisms underlying the association\*: Exploring the potential mechanisms by which hyperuricemia may contribute to the development and progression of NAFLD and liver fibrosis in adult obese patients.

Single and Multiple Dose Escalation of PHIN-214 in Child-Pugh A and B Liver Cirrhotics

This 2-part study will evaluate PHIN-214 given as a single one-time dose (Part 1) and in multiple doses (given as daily doses for 28-days) (in Part 2). Specifically, this study evaluates PHIN-214, to determine the safety, tolerability, and pharmacokinetic effects of PHIN-214, and to establish the maximum tolerated dose or optimal beneficial dose in patients with Child Pugh A and B Cirrhosis.

Fibrosis Lessens After Metabolic Surgery

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment. Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.

Evaluation of Non-Invasive Tests for Metabolic Liver Disease

The Non-Invasive Biomarkers for Metabolic Liver Disease (NIMBLE) study is a comprehensive, multi-year collaborative effort to standardize, validate and advance the regulatory qualification of blood- and imaging-based biomarkers to diagnose and stage Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH). MASH is characterized by liver inflammation accompanied by simultaneous fat accumulation in the liver.

Community Screening and Management of Hepatitis B, C and Delta in the Mongolian Population Living in France

In Mongolia, mortality from hepatocellular carcinoma (HCC) is one of the highest in the world. Viral hepatitis is the main cause of HCC: the prevalence of hepatitis B (HBV) estimated at 11% In Mongolia, hepatitis C (HCV) at 8.5%, and hepatitis Delta (HDV) at 40-60% in HBV-infected patients. Viral hepatitis are essentially asymptomatic and therefore require systematic screening for diagnosis. Once a diagnosis of chronic viral infection has been established, specific therapies are available to reduce the morbidity and mortality of these patients. A study carried out in California in the Mongolian community found an HBV prevalence of 9.7% and positive HDV serology in 41% of these patients. There is a large Mongolian community in France, estimated at between 5,000 and 6,000 patients. Although the majority of these patients are covered by French social security; however, access to care and screening for viral hepatitis often remain difficult and insufficient for migrant or vulnerable populations in France The aim of this study is to screen the Mongolian community in France for viral hepatitis, and then initiate a program of care and treatment.

Clinical Outcomes of Early Kasai Surgery With Umbilical Cord MSCs in Biliary Atresia

The goal of this clinical trial with historical control is to evaluate whether umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy can improve clinical outcomes in infants with biliary atresia undergoing Kasai surgery before 90 days of age. The main questions it aims to answer are: Does UC-MSC therapy improve liver function parameters (bilirubin, albumin, liver enzymes, coagulation profile)? Does UC-MSC therapy reduce complications such as anemia, ascites, jaundice, and improve PELD scores? Does UC-MSC therapy improve overall survival compared to standard Kasai surgery alone? Researchers will compare the group receiving UC-MSC in 2025-2027 with a historical control group of patients who previously underwent Kasai surgery without UC-MSC therapy. Participants will: Undergo preoperative evaluation, including laboratory and imaging tests. Receive Kasai surgery combined with intraoperative trans-portal vein injection of 20 million UC-MSCs. Be monitored postoperatively through serial laboratory tests, imaging (Fibroscan), and clinical assessments at scheduled intervals. Be followed up for potential serious adverse events and survival outcomes.

Hydronidone Capsules in Long-term Treatment in Patients With Chronic Viral Hepatitis B Liver Fibrosis

This study is a Phase IIIb extension trial following the "A Randomized, Double-blind, Placebo-controlled, Multicenter, Entecavir-based, Phase III Clinical Trial of Hydronidone Capsule in the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B". The main objective of this study is to evaluate the effectiveness and the safety of hydronidone capsules for long-term treatment of patients with chronic viral hepatitis B liver fibrosis.