Clinical Research Directory

Copper Supplementation in Cirrhosis

End stage liver disease or cirrhosis is a major cause of mortality in the United States and the world. Other than targeting the underlying cause, such as alcohol cessation and antiviral therapy, very few medical treatments can change the natural history of cirrhosis. Malnutrition is one of the few potentially modifiable factors that have been associated with cirrhosis severity and poor prognosis. The transition metal copper (Cu) is an essential trace metal that must be acquired from diet. Its metabolism is primarily regulated by the liver in its role as a master regulator of nutrients. In 2019, the investigators reported that Cu deficiency defined by below normal serum or liver concentrations occurred in a wide range of liver disorders and was associated with a severe disease phenotype. Improvement in liver function was observed in 2 of the 3 patients who received Cu supplementation. In 2023, the investigators conducted a longitudinal cohort study utilizing clinical, serum and liver explant tissue data from 183 cirrhosis patients. The investigators showed that Cu deficiency was associated with 2-fold higher infection rate and a more than 3-fold increase in the risk of death compared to patients with normal Cu status. These preliminary findings and the well-established importance of Cu in human health prompted the investigators to design the current pilot randomized, placebo-controlled, crossover trial to determine the effect of Cu supplementation on Cu dependent biochemical changes, patient safety and patient reported outcomes in cirrhosis.

FAST-IRM for HCC suRveillance in pAtients With High risK of Liver Cancer.

Intro: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. In France, more than 10,000 new cases are identified each year. The latter occur in 85% of cases in cirrhosis, the most frequent causes of which are excessive alcohol consumption, metabolic syndrome or HBV/HCV infection. Patients with cirrhosis justify being included in monitoring programs involving the performance of a semi-annual liver ultrasound (US) in order to detect HCC eligible for curative treatment (liver resection or percutaneous ablation). This practice is considered to be cost-effective in the event of an annual incidence of HCC\> 1.5%. US in this context has a low sensitivity for the detection of HCC at the very early stage and the following observations have been made in the last 20 years: * The rate of patients detected at early stage BCLC 0 is around 30% by ultrasound * The rate of patients included in surveillance programs detected with advanced HCC eligible for palliative treatment is around 20% * Reducing the periodicity of liver ultrasounds from 6 to 3 months does not improve these results. In parallel, liver MRI has been evaluated as a tool for the early detection of HCC. Its performance for the detection of HCC at the very early stage exceeds 80%. However, due to the higher cost compared to US, it was estimated that its use in screening context would only be cost effective in the event of an annual incidence\> 3%. In addition, the practice of these expensive and long-lasting MRIs (30 to 45 minutes) can be optimized by carrying out abbreviated MRI protocols" or Fast-MRI: short protocols (\<10 minutes), based on the sequences with the better detection sensitivities (Se\> 83%). The hypothesis is that Fast-MRI used as a screening examination in patients at high risk of HCC (\> 3% per year) could increase the rates of patients detected at an early stage accessible to curative treatment and demonstrate its cost-effectiveness in this population. Hypothesis/Objective: The main objective is to assess the cost / QALY and / patient detected with an early HCC BCLC 0 (single tumor \<2cm) by semi-annual monitoring by liver US and Fast-MRI, compared to conventional semi-annual monitoring by liver US alone in patients with cirrhosis and an anticipated HCC incidence\>3%. Conclusion: If positive, this trial could modify international practice guidelines and set MRI as the optimal tool for early HCC detection in high-risk patients.

An Observational Study of Patients With Chronic Liver Disease

TARGET-Liver Disease (TARGET-LD) is an observational research study to conduct a comprehensive review of outcomes for patients with chronic liver disease (CLD).

In Patients With Chronic Liver Diseases(Alcoholic Liver Disease and Non-Alcoholic Fatty Liver Disease), LAENNEC(Human Placenta Hydrolysate) is to Evaluate the Efficacy and Safety of Intravenous Drop

Control group : LAENNEC subcutaneous injection (4 ml) Experimental group : LAENNEC intravenous injection (10 ml)

To Study the Clinical Course and Outcomes of Non-electively Hospitalised Patients of Chronic Liver Disease (CLD) With Hepatic or Extra-hepatic Predominant Organ Failure(s) at 6 Months.

Title - To study the clinical course and outcomes of non-electively hospitalised patients of chronic liver disease (CLD) with Hepatic or Extra-hepatic predominant organ failure(s) at 6 months. Summary - ACLF is a condition where acute insult leading to worsening liver failure with or without extra-hepatic failure leads to a high short-term mortality. However, the presence of cirrhosis, prior decompensation, non-hepatic/systemic acute insult, organ failure and treatment are different in different part of the world. This is due to in-homogenous patient cohort. The current study was planned for all patients of CLD, who were non-electively hospitalized and were followed up for long-term to identify the differences in clinical course, acute insult, organ failure, therapy and outcome in relation to liver failure with or without extra-hepatic organic failure. In the study the laboratory, clinical parameters, inflammatory and regenerative markers will be evaluated as a marker of disease progression, reversal, recompensation or regression. This will enable us to differentiate the ACLF between east and west, guide us for defining the natural course of CLD with failure.

Measuring Patient Reported Needs in Outpatient Liver Disease Management

This prospective study aims to assess health-related social needs (HRSNs) among patients with chronic liver disease (CLD) receiving outpatient care at Indiana University Health. Patients with CLD often face socioeconomic challenges that adversely affect health outcomes, but no validated screening tool exists for this population. The primary objective is to measure the prevalence and types of HRSNs in CLD patients. Secondary objectives are to evaluate patient preferences regarding provider involvement in addressing social needs, explore reasons for declining assistance, and assess provider perspectives on incorporating HRSN data into clinical care. A total of 200 adult patients with CLD and their visit providers will be enrolled. Participants will complete surveys on demographics, HRSNs, health literacy, quality of life, social support, and patient activation, with medical data supplemented from chart review. Providers will complete surveys about their experiences using HRSN data in routine practice. Results will describe unmet social needs in this population, patient and provider attitudes toward screening, and inform strategies for integrating HRSN assessments into liver disease management and routine healthcare delivery.

Endoscopic Ultrasound Shear Wave Elastography Study

This study shall be a prospective, multicenter, single arm, consecutive, interventional study conducted in a post-market setting using commercially available devices. Consecutive, eligible patients with clinical suspicion of MASLD or MASH reporting for an endoscopic ultrasound and liver biopsy for evaluation of fibrosis will be enrolled. EUS Shear Wave Elastography and Attenuation Imaging technologies will be compared to liver biopsy and FibroScan results and other non-invasive fibrosis screening modalities . The data collected during this study will be evaluated in accordance with the procedures set forth in the protocol. The main question\[s\] it aims to answer are: * Establish optimal cutoffs for EUS-SWE in reference to liver biopsies staging system for liver fibrosis * Evaluate the diagnostic performance of EUS-SWE compared to FibroScan (VCTE) and to other non-invasive fibrosis screening modalities (screening scores). Participants will undergo: * Endoscopic Ultrasound with Shear Wave Elastography (SWE) and Attenuation Imaging (ATI) * Liver biopsy * FibroScan

hepatomiR cACLD Study

This study looks to gather data on hepatomiR, a CE-certified test already intended for gauging liver-related outcomes, in order to define a cut-off regarding specific decompensation events (ascites, variceal hemorrhage, hepatic encephalopathy) in chronic liver disease (CLD). Based on these data, it is aimed to advance the current understanding of factors driving decompensation, with potential repercussions for future risk management and therapy.

VIATORR Device Registry

The primary objective is to confirm the clinical performance and safety of the GORE® VIATORR® TIPS (Transjugular Intrahepatic Portosystemic Shunt) Endoprosthesis with Controlled Expansion throughout the device functional lifetime of 3 years in real world setting. The secondary objective is to collect information on quality of life after treatment with the GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion. Additionally, data will be collected on the safety and performance of the GORE TIPS Set when utilized.

Mobile Chat Messaging for Alcohol Reduction in Patients With Chronic Liver Diseases

The goal of this pilot randomized controlled trial is to evaluate the trial feasibility and acceptability of mobile chat messaging for reducing alcohol use among patients with chronic liver diseases. Specific objectives include: 1. To assess whether the eligibility criteria were too restrictive by estimating the eligibility rate 2. To assess how many eligible CLD patients accepted the invitation to participate in the trial 3. To assess the participant retention rate through 6 months after treatment initiation 4. To assess the intervention acceptability in terms of participants' engagement with and rating of the chat messaging intervention. 5. To assess the safety of the intervention 6. To estimate the intervention effect on alcohol use outcomes and liver functions 7. To synthesise data to inform the sample size calculation in the future definitive trial 8. To explore the participants' perception and experiences in the chat-based intervention

D-SOLVE Cohorts (Cohort a and B)

Hepatitis D is by far the most severe form of chronic viral hepatitis, frequently leading to liver failure, hepatocellular carcinoma and death. Hepatitis D is caused by coinfection Hepatitis D is caused by co-infection with hepatitis B virus (HBV) and hepatitis D virus (HDV). This multicenter cohort should enable a comprehensive and unbiased biomarker screening of well-defined HDV-infected patients, followed by mechanistic studies to determine the functional role of distinct molecules. Patient surveillance strategies and antiviral treatment approaches could be personalized which should reduce clinical and social disease burden, improve quality of life and save direct and indirect costs caused by HDV infection.

Effect of Perioperative Oral Rifaximin on Early Graft Dysfunction in Adult Living Donor Liver Transplant

Liver transplantation has been a lifesaving treatment for individuals with end stage liver disease and acute liver failure. However, initial poor function of a liver allograft after liver transplantation, termed early graft dysfunction (EGD), has been associated with increased allograft loss or mortality after transplantation. EGD in LDLT is multifactorial. Factors affecting EGD are GRWR, ischemia reperfusion injury, recipient metabolic demand, graft quality, graft inflow and outflow. Studies shows that the incidence of EGD is 15-38%. It is associated with increased allograft loss \&amp; mortality. Rifaximin is an antibiotic that reduces EGD by 50% as shown by 2 studies but this study was done in DDLT setting and rifaximin was given in the pretransplant group. In this investigators will study the effect of perioperative oral rifaximin on early graft dysfunction in adult living donor liver transplant.

Albumin Modifications as Early Biomarkers of Chronic Liver Diseases

Chronic liver diseases, affecting over 800 million people worldwide, lead to approximately 2 million annual deaths. The need for early, sensitive diagnostic strategies to prevent disease progression and reduce mortality is still unmet. The traditional serum markers lack sensitivity and specificity, leading to the integration of these biomarkers into panel tests with algorithms or imaging measures. Despite their widespread use, these tests have limitations at an individual level, including an inability to predict disease progression or response to treatment. To address these shortcomings, our project proposes utilizing albumin post-translational modifications (PTM) as a predictive biomarker for liver disease progression. The hypothesis is that albumin modifications occur in the early stages of hepatocellular damage and are indicative of future liver diseases. These modifications can be detected through serum albumin isoform determination, albumin isoforms profiles or the albumin's ligand-binding capacities. Innovatively, the study will use the Serum Enhanced Binding (SEB) test, which identifies reduced ligand-binding capacities, and discusses a second patent for determining a typical isoform profile based on the hepatic injury type. Our preliminary results from animal models and a proof-of-concept studies with patients support this hypotheses. Our previous studies demonstrated also significant differences in albumin isoform profiles in response to different types of hepatic injury and high sensitivity and specificity in the SEB test among cirrhotic patients. The primary objective of the MALAHBAR project is to evaluate the capacity of albumin PTM to predict liver disease progression over three years in chronic liver disease patients. Secondary objectives include assessing the predictive ability of different albumin isoforms and the SEB test for liver disease progression, evaluating diagnostic performances and confirming characteristic albumin isoform profiles related to specific hepatic injuries. The study could represent a significant advancement in liver disease diagnostics and management, offering new insights into the role of albumin in liver pathology.

Efficacy of Plasmapheresis in Patients of Drug-Induced Liver Injury (DILI) With Underlying Chronic Liver Disease

DILI is an underdiagnosed and under appreciated causal or contributing factor to liver injury. DILI can mimics features of the entire spectrum of acute and chronic liver disease. Asia-Pacifc region is characterized by two unique features; the high prevalence of tuberculosis (TB) in the population and the ubiquitous use of traditional and complimentary medicines.Current definition of Hy's law presents significant difficulties when dealing with patients with preexisting CLD in clinical trials. Hallmark of the hepatic manifestation in these patients is hyperbilirubinemia and coagulopathy rather than ALT elevation.

EUS vs TJ for Liver Biopsy and Portal Pressure Gradient Measurement

This study will directly compare the endoscopic ultrasound guided approach to obtain adequate liver biopsies and portal pressure gradient measurements to the current standard of care which uses the transjugular approach.

Comparison Between 2-dose Versus 3-dose Regimens of Heplisav B in Cirrhosis

Investigators want to compare the seroconversion rates between two-dose and three-dose regimens of the hepatitis B vaccine (Heplisav B) among patients with cirrhosis, a randomized prospective study.

Somatic Mutation in Chronic Liver Disease

Deaths from chronic liver disease are rising in the UK and around the world. The leading causes are alcohol-related liver disease, metabolic-dysfunction associated steatotic liver disease (MASLD, formerly known as 'non-alcoholic fatty liver disease') and viral hepatitis. Chronic liver disease puts people at significantly increased risk of liver cancer, which in the UK has a 5 year survival of under 15%. Little is understood about how liver cells acquire genetic changes, called somatic mutations, as they progress from healthy cells, to disease, to cancer development. This study aims to investigate these somatic mutations across different causes of chronic liver disease, and different stages of liver disease. The investigators hope this will help us to understand how different insults to the liver put the liver cells under different pressures, resulting in varying genetic changes. By understanding these changes specific to disease aetiology and stage, novel genetic targets may be identified which assist to focus research in identifying specific prognostic, diagnostic and therapeutic tools in chronic liver disease, and improve outcomes for patients. Tissue, surplus to clinical requirement, from patients were undergoing liver biopsy, liver resection or liver transplantation (tissue sampling from explanted liver) collected by collaborators at University of Texas Southwestern will undergo genomic sequencing at the Wellcome Sanger Institute.

Study on the Efficacy and Safety of Avatricopal in Patients With CLD Complicated With Thrombocytopenia

In this study, patients with chronic liver disease undergoing selective invasive and minimally invasive surgery combined with thrombocytopenia were enrolled. After enrollment, liver disease treatment was supplemented with avatripopal for 5 days. Biochemical indexes of avatripopal were monitored during treatment and after withdrawal. The proportion of patients with platelet count ≥50×10\^9/L on the day of selective invasive and minimally invasive surgery was analyzed. The incidence of adverse events was observed.

Referral of Patients to Hepatology With Hepatoscope

Patients identified as being at risk of liver fibrosis because of a positive Fibrosis-4 (FIB-4) test in the primary care setting will be offered be enrolled in the trial and to undergo an Hepatoscope exam (external non-invasive ultrasound imaging exam) to screen for liver fibrosis (with stiffness measurements) and/or steatosis (with ultrasound parameters related to fatty liver). All patients presenting with a liver stiffness value of at least 6.5 kilopascal (kPa) will be referred to the tertiary hepatology consultations for further assessment. Hepatoscope measurements will be compared to the standard of care for these patients, as defined at the tertiary hepatology center.

Evaluating the Diagnostic and Predictive Value of Non-invasive Tests (NITs) on the Progression of Chronic Liver Disease.

Primary objective is to study the relevance of non-invasive test (NITs) in predicting disease stage (diagnostic biomarker) and outcome (predictive biomarker) in patients with suspected or established liver disease and cirrhosis.

Prognosis Value of Non-invasive Methods for the Diagnosis of Chronic Liver Disease

The aim of this retrospective and prospective study is to evaluate the 20-year prognosis value of non-invasive methods for the diagnosis of chronic liver disease for predicting survival and complications of cirrhosis.

An Observational Study Evaluating Patients With Chronic Liver Diseases Associated With Hepatic Steatosis

Hepatic steatosis may cause inflammation and fibrosis within the liver potentially leading to end-stage liver disease cirrhosis, liver failure and death. The condition is associated with several other chronic liver diseases like autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, hereditary hemochromatosis and alpha-1-antitrypsin deficiency and may also develop secondary to other diseases like inflammatory bowel disease and chronic pancreatitis. Diagnosing chronic liver diseases can be challenging and treatment may be limited. In-depth phenotyping at a tissue level may generate insight into the underlying pathophysiology of diseases and furthermore identify common as well as specific diagnostic biomarkers and future treatment targets of the diseases. We therefore undertake a study that evaluates patients with chronic liver diseases associated with hepatic steatosis.

Nottingham Community Liver Biomarkers Cohort

Deaths due to advanced liver scarring (liver cirrhosis) continue to increase, and liver disease is now the 3rd leading cause of premature death in the United Kingdom. The majority of liver disease is lifestyle related (alcohol, obesity and associated type 2 diabetes, injecting drug use) and therefore reversible if caught at a precirrhosis stage. However, current liver function blood tests are poor inadequate, and subsequently a large burden of liver disease is currently missed. A variety of noninvasive liver biomarkers (blood and imaging tests) have been developed which identify liver disease accurately at earlier stages of scarring. The identification of liver disease in the community, where previous studies have discovered a large burden of previously unidentified but significant liver disease, is therefore a feasible place to develop new liver disease investigation pathways using these noninvasive markers. In collaboration with the Department of Health, Nottingham University Hospitals have commenced a pilot community liver disease pathway in two General Practices in Nottingham in February 2012. Patients with liver risk factors (hazardous alcohol use, obesity or type 2 diabetes)are invited to take part in the pathway. Patients undergo a simple blood test (AST:ALT ratio and BARD score), with a high test result requiring referral for a liver stiffness scan (Fibroscan)which is performed in the community setting. High threshold scan values are reviewed by a consultant liver specialist in a community liver clinic. Preliminary findings show that the pathway accurately identifies patients with early liver scarring and previously unidentified significant liver disease. The participating General Practitioners have also noted a striking number of patients finally engaging in important lifestyle changes following pathway implementation. A second phase of the pilot pathway, in 2 Inner City General Practices with a total practice population of c.14,000 patients commenced in June 2013. We have subsequently designed this cohort study, where pilot participants will be consented for follow up over a long period. We will assess future liver-related and cardiovascular events (including death), and perform qualitative patient interviews to assess the reasons for and persistence of lifestyle changes after liver disease investigation. We hypothesize that stratification of liver disease in the community will unearth a significant amount of previously undetected but significant chronic liver disease. Moreover, we will evaluate whether stratification of liver disease using these tests predicts future liver and cardiovascular disease and death, and whether stratification has an impact on patient's future lifestyle choices.