Clinical Research Directory

Incidence of Post TIPS/DIPS Heart Failure and the Factors Associated With Post-TIPS/DIPS Heart Failure.

The creation of a transjugular intrahepatic portosystemic shunt (TIPS) or direct intrahepatic portosystemic shunt (DIPS) results in an acute increase in venous return and cardiac preload. These procedures are established therapies for refractory ascites, variceal bleeding, hydrothorax, and Budd-Chiari syndrome, they may unmask subclinical cardiac dysfunction. Incidence of heart failure after TIPS varies widely from 0-25%, reflecting heterogeneity in patient selection and the lack of prospective data. Several predictors-including elevated pre-procedure BNP/NT-proBNP, diastolic dysfunction (E/e' \>10, LAVI \>34 mL/m²), impaired GLS, and elevated right-sided pressures-have been described, but most evidence arises from retrospective studies with inconsistent definitions.This single-center prospective cohort study at ILBS aims to determine the true incidence of heart failure within 6 months of TIPS/DIPS and to identify independent predictors using comprehensive clinical, biochemical, echocardiographic, and invasive hemodynamic parameters. Heart failure is a clinical syndrome with symptoms and/or signs caused by structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. In Echocardiography parameters GLS\<18 post TIPS for systolic function, E/e' average \> 15 for diastolic function will taken into consideration. In case of worsening diastolic function increase in grade of diastolic dysfunction ( measured by E/A)will be considered as post TIPS worsening.A total of 127 patients will be enrolled based on sample-size calculations assuming a 5% event rate. Findings will help create a clinically applicable predictive model to guide pre-TIPS cardiac risk stratification and optimize patient selection, thereby reducing morbidity and improving outcomes.

Coronavirus Disease 2019 (Covid-19) Impact on Alcohol-related Liver Disease Patient Outcomes, Care and Alcohol Use

The study consists of a randomized controlled trial evaluating the efficacy and feasibility of a stepped alcohol treatment using telemedicine on unhealthy alcohol use in patients with chronic liver disease receiving care in hepatology practices at three sites. Patients who meet eligibility criteria will be randomized to one of two study arms: 1) Stepped Alcohol Treatment (SAT) or, 2) Usual Care (UC). Participants will be randomized separately by site. SAT includes 3 sessions of motivational interviewing followed by referral to addiction medicine for patients who do not reduce unhealthy drinking. Trial outcome measures will be complete at 6 and 12 months following baseline enrollment.

Biomarker-guided Reduction of Immunosuppression in Liver Transplant Recipients (BRITRE)

Researchers are interested in determining whether it is safe to reduce anti-rejection medication by approximately 50% after liver transplantation and whether special blood tests called biomarkers can identify early signs that the body is starting to attack the new liver before it gets hurt.

RTX001 Autologous Engineered Macrophages for Liver Cirrhosis

The purpose of this study is to assess the safety and efficacy of RTX001 in patients with end-stage liver disease. This study is the first time RTX001, a macrophage cell therapy engineered to have an anti-inflammatory and anti-fibrotic effect, will be given to humans.

Everolimus bAsed caLcineurin inhibiTor frEe immunosuppRession oNe Year AfTer lIver transplantatiON (ALTERNATION)

The overall aim of this study is nephroprotection based on a calcineurin inhibitor (CNI)-free therapy beyond year one after orthotopic liver transplantation (OLT) in highly pre-selected patients with low rejection risk.

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension; Renewal

This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort. Cohort 1: Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity \[Lantheus Medical Imaging, N Bilerica, MA, USA\] and Sonazoid \[GE Healthcare, Oslo, Norway\] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm. Cohort 2: Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting. Cohort 3: Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension. Cohort 4: Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.

A Study to Evaluate the Pharmacokinetics and Safety of INCB161734 in Participants With Hepatic Impairment

This study is conducted to evaluate the pharmacokinetics and safety of INCB161734 in participants with hepatic impairment.

Liver Micro Flow - MRI

This study integrates and evaluates a series of novel MRI methods for quantifying blood perfusion and tissue microstructure. The proposed perfusion and microstructure measures may provide biomarkers for fibrosis, cirrhosis, portal hypertension, and response to treatment. The precision of these methods will be evaluated in 110 participants, including healthy volunteers, people with chronic liver disease (CLD), and people with liver fibrosis.

RESTORE Declined Livers Study

This is a prospective, non-randomized, clinical trial of discarded liver transplants that have received normothermic machine perfusion (NMP), compared with standard cold preservation liver transplants. The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study. Liver transplant outcomes will be ascertained during 12 months post-transplantation. The results of the trial will be compared with those of contemporary comparison groups of patients who received the standard criteria donor liver transplantation.

Global Utilization And Registry Database for Improved preservAtion of doNor Livers

The objective of this registry is to collect and evaluate various clinical effectiveness parameters in patients with transplanted donor liver that were preserved and transported within the LIVERguard system, as well as retrospective standard of care patients

Observational Pharmaco-Epidemiology Research & Analysis

Greater advances are needed in two separate but related areas in healthcare: 1) the Clinical Decision Support Systems that complement the EHR use in support of routine patient care, population management and disease management; and 2) the use of the point-of-care observational data from the provider-patient encounter that support realworld medical research and healthcare quality measure assessment. Real-world evaluations of treatments of chronic diseases in the context of comorbid conditions and special populations (minorities, women, mentally ill, and those with addiction) are limited. The purpose of the OPERA database is to help address this unmet need in clinical research.

Liver Function Test Abnormalities in Pediatric Type 1 Diabetes

This cross-sectional study aims to determine the frequency, pattern, and predictors of liver function test abnormalities among children and adolescents with type 1 diabetes mellitus attending Assiut University Children Hospital.

Effect of Synapse Medicine Decision Support on Inpatient Pharmacist Efficacy and Efficiency

Adverse drug events (ADE) are common and dangerous in the hospital and following discharge to the ambulatory setting. One cause of ADEs in both settings is medication regimen inappropriateness, including polypharmacy, drug-drug interactions, and medications that are inappropriate or inappropriately dosed given patients' age, renal, and hepatic function. Hospitalization provides a good opportunity to investigate medication appropriateness given new or worsening conditions and available expertise. Inpatient pharmacists are medication experts and often round with medical teams, but they may not always have all the information available at their fingertips to make optimal recommendations regarding medication appropriateness for each patient. Clinical decision support to pharmacists at the point of care has potential to improve the speed, quantity, and quality of medication recommendations to inpatient teams; any subsequent improvements to medication regimen appropriateness have the potential to reduce ADEs in the hospital and after discharge. Specific Aims and Objectives Aim 1: Implement real-time decision support regarding medication regimen appropriateness among pharmacists who round with inpatient medical teams. Aim 2: Determine the effects of this intervention on the number of medication regimen recommendations and time spent per recommendation Aim 3: Evaluate the use and usability of the decision support tool and develop strategies to mitigate barriers and promote facilitators of implementation using mixed methods implementation science approaches.

Assessment of Microorganisms and Host Response In Liver Diseases

The normal human gut is home to millions of microbes including bacteria, fungi, and viruses, collectively forming the gut microbiota, which exists in harmony within us. Much research is still required to fully understand the contribution of microbes resident in the large intestine in liver diseases. The liver receives blood from the gut carrying all the necessary nutrients needed for our body but also has to deal with toxins derived from the microbes residing in the intestines. The gut microbiota is altered in liver disease. We still do not know clearly how this change impacts liver function and the health of liver patients. The purpose of our study is to answer this question by assessing the gut microbiota using modern microbiological and molecular methods. By studying the alterations in the gut microbiota in patients with liver disease we can understand how they affect our immune system and metabolism. This will help design novel medicinal products to prevent and treat liver disease.

Liver Cancer Prevention Randomized Control Trial

To determine the effectiveness of a behaviorally-based tailored disease management intervention in patients with fibrosis or steatosis and risk factors for cirrhosis.

Implementation of a Digital Clinic for Alcohol-associated Liver Disease and Alcohol Use Disorder (DALC)

The purpose of this study is to determine whether a multidisciplinary digital clinic will improve health outcomes, reduce costs, increase access, and improve provider satisfaction. The primary aim of this study is to improve clinical outcomes in patients with ALD through the implementation of a novel digital health platform for personalized multi-disciplinary treatment of patients with ALD and AUD. Secondary aims include improvement in provider and patient-reported outcomes including satisfaction with AUD treatment.

Development of a New Method for Liver Stiffness Measurement Using FibroScan

This is an European, prospective, interventional, multicenter clinical investigation that will take place in 2 French sites. 153 adults patients will be included. The study objective is to develop a new method for measuring liver stiffness using FibroScan.

Development of a FibroScan Liver Examination Using a Single Probe

This is an exploratory, international, prospective, interventional, multicenter clinical investigation that will take place in 1 Hong Kong site and 3 French sites and 309 adults patients will be included. The study objective is to assess the LSM reproducibility between the FibroScan examination performed with the Single Probe (SP) and the FibroScan examination performed with the reference probes (M and XL).

Normal Liver Stiffness by MR Elastography

Healthy children will be recruited to under Magnetic Resonance Imaging (MRI)along with MR elastography to determine normal liver stiffness values.

Patients With Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is frequently diagnosed at an advanced stage, resulting in limited therapeutic options. Despite the advances in immunotherapy, a substantial proportion of patients fail to respond adequately due to mechanisms of immune resistance. The gut microbiota plays a crucial role in modulating the response to immune checkpoint inhibitors (ICIs), and fecal microbiota transplantation (FMT) has demonstrated the ability to enhance their efficacy in other tumors, such as melanoma. In patients with HCC and cirrhosis, intestinal dysbiosis, characterized by a reduction in beneficial bacteria (e.g., Bifidobacterium, Akkermansia) and increased inflammation, is associated with an immunosuppressive profile. Furthermore, a dysbiosis index has been correlated with response to ICIs. In this context, FMT represents a promising strategy to enhance the efficacy of immunotherapy in HCC, although data regarding its efficacy and safety are still limited.

Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)

Hepatocellular carcinoma (HCC) is the 7th most common cause of cancer death globally but only 20% are diagnosed in its early stages where cure is possible. Current standard-of-care surveillance of patients at high risk of developing HCC with 6-monthly serum alpha-fetoprotein (AFP) and ultrasound imaging (US) has a sensitivity of approximately 63% for detecting early HCC. There is an urgent need for a more efficacious and convenient modality of surveillance of high-risk patients to diagnose HCC at an early stage. This prospective study aims to address this unmet clinical need by validating a panel of circulating miRNA biomarkers to develop an in-vitro diagnostic (IVD) kit for the detection of early HCC in a cohort of high-risk patients. Additionally, this study also aims to develop a multi-parametric MRI-based AI algorithm to quantify individual risks of developing HCC and to predict the progression of chronic liver disease in this cohort to enable targeted surveillance. Lastly, by identifying changes in the microbiome and metabolites as HCC develops in this cohort enables the establishment of actionable biomarkers that can prevent and predict the development of HCC.

Primary Sclerosing Cholangitis in Children

Primary sclerosing cholangitis (PSC) is a rare liver disease that damages the liver's bile ducts. Bile ducts are tiny tubes that carry bile from the liver to the small intestine. Bile is a liquid produced by the liver that helps us absorb and use the nutrients in the food we eat. In people with PSC, the bile backs up into the liver and will damage it, causing scarring of the liver. The purposes of this study are to: * Collect medical and other data to learn more about PSC, how it progresses, and identify factors that may cause the disease to progress more quickly. * Ask questions about how PSC symptoms affect your child's life to learn more about its impact on your child's daily functioning * Children with PSC who are seen at one of the participating clinical sites in the Childhood Liver Disease Research Network (ChiLDReN) will be asked to contribute information, DNA, and other specimens. The information and specimens will be available to investigators to carry out approved research aimed at learning more about the possible causes and long-term effects of PSC.

Genetic Collection Protocol

This study involves the one-time collection of whole blood or saliva samples for the extraction and storage of DNA for use in ongoing and future ChiLDReN studies.

Early Liver Disease Breath Detection

The Early Liver Disease Breath Detection Study is a cross-sectional study where subjects with advanced liver fibrosis will ingest a mixture of food-grade compounds (known as Exogenous Volatile Organic Compound or EVOCs) in the form of an emulsion and then provide multiple breath samples. These EVOCs can be measured on exhaled breath and it has been found that liver diseases can affect the way EVOCs are processed in the body. The objective is to identify if changes in the way these EVOCs are processed in the body can have the potential to diagnose early stage liver diseases for these subjects. Subjects with fibro-scan confirmed fibrosis will be recruited from Norfolk and Norwich University Hospital (NNUH) by local research staff, they will be invited to take part in the study at a dedicated clinic at OneNorwich Practises a clinic based in Norwich City Centre. They will be asked to fast overnight then provide a baseline breath sample, before ingesting the food-grade EVOCs emulsion and then providing additional breath samples at subsequent time points up to 90 minutes post ingestion.