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 supplement's 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 investigator’s 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 effects of a new herbal formulation called Melats P for women with Polycystic Ovarian Syndrome (PCOS), a common metabolic disorder affecting women of childbearing age. PCOS causes problems such as hormonal imbalance, irregular ovulation, infertility, obesity, excessive hair growth, acne, and metabolic issues like insulin resistance and type 2 diabetes. This study aims to compare the herbal formulation against conventional treatment and their combination in improving infertility and menstrual cycle regulation in women with PCOS. Participants will be divided into three groups: one receiving the herbal formulation Melats P at 500 mg twice daily, another receiving Metformin XR 750 mg twice daily, and a third group receiving both treatments together. Each treatment is given for 4 months. The herbal formulation contains plant-based ingredients chosen for their potential to restore hormonal balance and improve ovulation with fewer side effects compared to standard drugs. The study includes a phase 1 clinical trial design with randomized assignment and no masking. During the study, participants will have their menstrual cycle regulation monitored from baseline to 4 months. Additional assessments include blood tests for hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, as well as metabolic measures like glycated hemoglobin (HbA1c), fasting insulin levels, insulin resistance (HOMA-IR), and body weight. These evaluations will occur at the start and after 4 months of treatment to assess safety and effectiveness. The total participation duration is approximately 4 months, with the study scheduled to start in February 2025 and end by March 2026.

Researchers are conducting a retrospective study to analyze complications following hepatectomy, a key surgical treatment for liver diseases like liver cancer, hepatic hemangiomas, and biliary stones. While hepatectomy has shown significant benefits, postoperative complications such as liver failure, hepatic vascular thrombosis, wound infections, and bile leakage remain serious concerns that threaten patient health and increase treatment costs. Prior studies have mostly focused on isolated complications with small patient groups, lacking a comprehensive overview. This observational study uses diagnostic criteria from the International Study Group for Liver Surgery (ISGLS) to identify liver failure occurring on or after the fifth day following surgery. The study groups patients into those who experienced post-hepatectomy liver failure (PHLF) and those who did not, as well as patients with and without liver cirrhosis. The research collects data retrospectively from patients who underwent liver resection surgery at participating centers. Participants' medical records will be reviewed to assess the incidence and risk factors of complications after hepatectomy. The primary outcome is the occurrence of liver failure after surgery, with mortality evaluated within 30 days post-operation. The study aims to provide clinical doctors with better guidance on preventing and managing postoperative complications by analyzing a large patient sample. The study includes adults aged 18 to 80 years who had liver surgery and excludes patients with prior cancer treatments, repeat surgeries, other malignancies, severe concurrent diseases, or incomplete data.

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 physician's guidance at the UPMC Children's 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 empagliflozin's 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.