Tyrosinemia

Researchers are evaluating the effects of Diaberine, a berberine-based nutraceutical, on blood sugar regulation and metabolism in adults with metabolism disorder. This randomized, triple-blind, placebo-controlled trial will study 80 participants aged 18 to 70 over 24 weeks to assess how well this dietary supplement may aid in these health areas. Participants will be randomly assigned to one of two groups. One group will take Diaberine capsules containing Vitamin B12, berberine, magnesium citrate, cinnamon bark extract, chromium, and other ingredients three times daily, 15 minutes before meals. The other group will take placebo capsules with similar appearance but without the active ingredients. Both treatments will continue for 24 weeks with regular monitoring. During the study, participants will have their blood sugar regulation and metabolism measured at baseline, week 12, and week 24. Additionally, quality of life and weight changes will be tracked at multiple points throughout the 24 weeks. Participants will be monitored through questionnaires, blood tests, and weight assessments to evaluate the supplements effects and tolerance over time.

Researchers are investigating the relationship between the volume of normal liver tissue removed during surgery, called resected normal liver parenchymal volume RNLV, and the risk of liver failure after liver surgery post-hepatetotomy liver failure, or PHLF. This observational study focuses on patients diagnosed with hepatocellular carcinoma HCC or intracholangiocarcinoma ICC who have undergone liver resection. The goal is to build and assess a personalized predictive model using RNLV to better estimate the risk of PHLF before surgery. The study collects data retrospectively from over a thousand patients treated at the investigators center. Patients are grouped based on whether they developed liver failure after surgery, defined by two sets of criteria known as the 50-50 criteria and ISGLS criteria. The research evaluates how well the RNLV-based model predicts PHLF and compares its usefulness to other methods, especially for patients with large or multiple liver tumors. Participants medical records and surgical details are reviewed to calculate RNLV and assess liver failure outcomes within 30 days after surgery. The main outcome is the predicted probability of PHLF using the newly developed model. This approach aims to improve preoperative risk assessment to support safer liver surgeries. The study is sponsored by the National Natural Science Foundation of China and runs through the end of 2026.

This observational study focuses on liver transplant patients who are taking tacrolimus-containing medications. It aims to compare the pharmacokinetic parameters of different tacrolimus products and examine their relationships to liver function, kidney function estimated glomerular filtration rate, and patient adherence. The study also monitors the occurrence of acute graft rejection and infections such as BK and cytomegalovirus during the observation period. This research addresses the lack of real-life data on immunosuppressive drug effectiveness and safety in liver transplant patients across Europe. Participants are liver or simultaneous liver-kidney transplant recipients aged 18 years or older who have been on tacrolimus-containing immunosuppressant therapy for at least four weeks before joining. Various tacrolimus medications, including Envarsus, Adport, Advagraf, Modigraf, Prograf, and Tacforius, are used under routine clinical care following local dosing guidelines. The study observes patients over a 24-month period without changing their prescribed treatments. During the study, participants undergo routine clinical visits and tests as part of their standard care, with no additional procedures required. Researchers collect data on tacrolimus blood levels, daily doses, and their variability, alongside liver and kidney function tests. Adherence is assessed using the BAASIS questionnaire and electronic health records of prescription fills. Outcomes such as graft rejection, infection rates, and drug tolerability are evaluated over 12 months, with ongoing monitoring for up to two years.

Researchers are evaluating the use of ex vivo CRISPR-Cas9 genome editing on donor liver grafts to reduce immune rejection in patients with end-stage liver disease or acute liver failure. The study aims to create a hypoimmunogenic liver by knocking out HLA-A and HLA-B genes and disabling HLA class II expression through targeting the CIITA gene. This trial focuses on assessing the safety, feasibility, and immune response reduction of CRISPR-edited livers transplanted into patients. In this trial, deceased-donor livers undergo gene editing outside the body during machine perfusion using a CRISPR-Cas9 complex targeting HLA-A, HLA-B, and CIITA genes. The edited liver, confirmed for successful gene knockout, is then transplanted using standard surgical methods. Participants receive routine immunosuppressive therapy after surgery, with planned adjustments based on their response and graft immunogenicity. The study does not include a comparator group but compares outcomes to historical data of unedited liver transplants. Participants will be monitored closely with frequent visits to assess safety, graft function, immune response, and transplant rejection over time. Primary outcomes include adverse events, gene editing feasibility, and graft failure within 90 days. Secondary measures evaluate acute rejection, immune markers, graft survival, patient survival, immunosuppression reduction, and off-target effects up to 24 months. Long-term follow-up includes biopsies and immune monitoring, and participants are expected to comply with study procedures throughout the observation period.

Researchers are collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation HSCT using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physicians guidance at the UPMC Childrens Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease GVHD and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Hyponatremia, a common electrolyte imbalance in hospitalized patients, is classified into hypovolemic, euvolemic, or hypervolemic types. The syndrome of inappropriate antidiuresis SIAD often causes euvolemic hyponatremia, while congestive heart failure and liver cirrhosis are common causes of hypervolemic hyponatremia. Current treatments, including fluid restriction, have limited effectiveness. Researchers are evaluating the SGLT2 inhibitor empagliflozin Jardiance for its potential to increase serum sodium levels in these conditions through a randomized, placebo-controlled trial. Participants will receive either empagliflozin 25 mg or a placebo once daily by mouth for 30 days. The study is double-blind and randomized, comparing empagliflozins effects without additional fluid restriction. The trial aims to assess the impact of the drug on serum sodium concentration and other related measures over both short-term 4 days and longer-term 30 days periods. During the study, participants will undergo regular assessments including measurements of serum sodium, body weight, blood pressure, plasma and urinary markers, and various health and well-being indicators such as cognitive function, quality of life, and occurrence of symptoms like thirst or headache. Safety and clinical outcomes like hospital stay length will also be monitored. The total participation duration is 30 days, with detailed monitoring throughout this period.

Researchers are studying the use of an artificial liver support system ALSS to treat liver failure caused by immune checkpoint inhibitors in patients with hepatocellular carcinoma HCC. This condition arises in some patients receiving immune checkpoint inhibitors, a common treatment for advanced liver cancer, and can lead to severe liver failure requiring urgent treatment. The study aims to evaluate the safety and effectiveness of ALSS treatment to manage this serious liver complication. Participants are randomly assigned to one of two groups one group receives a combination of double plasma molecular adsorption system DPMAS and low volume plasma exchange LPE along with standard internal medical treatment, while the other group receives traditional plasma exchange PE with comprehensive internal medical treatment. Both treatments are given three times over two weeks, with specific volumes of plasma exchanged or adsorbed depending on the method used. During the 12-week study, researchers will monitor participants symptoms, laboratory test results, adverse events, and mortality rates. The main outcome measured is the mortality rate at 12 weeks, with additional assessment of liver function using the Model for End-Stage Liver Disease MELD score. This thorough follow-up includes regular clinical evaluations and laboratory tests to assess treatment impact and safety throughout the study period.

Researchers are studying patients with acute kidney injury AKI who require continuous renal replacement therapy CRRT, focusing on those with liver failure or significant liver dysfunction and severe shock. The goal is to understand how different causes of liver failure affect the safety and effectiveness of using citrate as an anticoagulant during CRRT. This retrospective cohort study aims to clarify the risks of citrate-related complications and compare treatment outcomes in this vulnerable population. Citrate anticoagulation works by binding calcium to prevent blood clotting in the CRRT circuit, and is usually processed by the liver. However, impaired liver function can cause citrate to build up, potentially leading to metabolic problems. This study will assess whether the cause of liver failure influences the frequency of such complications. It also compares kidney recovery, filter lifespan, and patient survival between patients with liver failure or dysfunction and those with severe shock. Participants medical records will be reviewed during their ICU admission to evaluate citrate-related safety outcomes and treatment effectiveness. Researchers will analyze data on metabolic status, filter performance, and survival rates. The study focuses on the time patients spend receiving CRRT in the ICU to measure these outcomes and gather insights on managing anticoagulation in this high-risk group.

Researchers are evaluating the effects of empagliflozin, a drug, on patients with cirrhosis and ascites. This proof-of-concept, placebo-controlled trial aims to explore how empagliflozin affects natriuresis sodium excretion and total body water over 14 days. The study also investigates its impact on neurohumoral activation and kidney blood flow in this patient group. Participants will be randomly assigned to receive either 10 mg of empagliflozin or a matching placebo for 14 days. After this treatment period, there will be a 14-day washout phase before participants switch to the alternate study drug for another 14 days. This crossover design allows comparison of empagliflozin and placebo effects within the same individuals. During the study, participants will undergo assessments to measure changes in sodium excretion and total body water at 14 days, as well as kidney blood flow and hormone levels from baseline to 6 hours and over 14 days. The study includes monitoring for safety and other health parameters. The total participation time covers the two treatment periods and the washout phase, lasting about 6 weeks in total.

Researchers are investigating the safety, side effects, and potential benefits of fecal microbiota transplantation in patients with liver failure. The study also aims to understand how this treatment affects the gut bacteria and the connection between the gut and liver immune system. The research intends to optimize fecal microbiota transplantation techniques to improve treatment outcomes for liver failure patients. Participants receive fecal microbiota transplantation every 5 days, with a total of four treatments given. This intervention involves transplanting healthy fecal bacteria to the patients intestines to study its effects on liver failure. The treatment schedule is fixed, with follow-up visits planned to monitor changes over time. During the study, participants will have blood and fecal samples collected before the first transplantation and at several points after treatment at 5, 10, 15, and 20 days, as well as 4 and 8 weeks later. These samples will help track liver and coagulation function, gut microbiota changes, immune system markers, and clinical symptoms. The study also observes safety and any adverse reactions throughout the follow-up period, providing a comprehensive view of the treatments effects over approximately two months.