Autoimmune Hepatitis

Researchers are studying the use of unlicensed cryopreserved cord blood units (CBUs) for transplantation in both pediatric and adult patients with various blood-related cancers and other disorders affecting the blood-forming system. This observational study aims to evaluate outcomes such as the recovery of a certain level of white blood cells after transplantation, as well as the incidence of infections, infusion reactions, survival rates, and graft-versus-host disease over time. The study involves patients receiving unlicensed CBUs at multiple U.S. transplant centers. These CBUs are used for patients with hematologic malignancies and other blood disorders. The protocol collects data on patients who receive these unlicensed transplant units, without administering a new treatment but observing the outcomes after transplantation. Participants will be monitored for neutrophil recovery at 60 and 100 days post-transplant, along with assessments of infection transmission, infusion reactions, survival one year after transplant, and occurrences of acute and chronic graft-versus-host disease. Platelet engraftment levels will also be tracked. The study includes patients of any age and follows them through the transplantation and recovery process to gather information on these key outcomes.

Researchers are studying the safety and how the body processes two drugs, AZD9550 and AZD6234, in people with different levels of liver problems compared to those with normal liver function. This Phase I, open-label study focuses on adults aged 18 to 85 who have severe or moderate hepatic impairment classified by Child-Pugh scores, as well as healthy controls matched for sex, age, and BMI. The study aims to understand how liver impairment affects these drugs' behavior in the body and their safety. Participants will receive a single subcutaneous dose of AZD9550 followed by a washout period, then a single dose of AZD6234. The study includes three groups: those with severe hepatic impairment (Child-Pugh Class C), moderate hepatic impairment (Class B), and healthy individuals with normal liver function. The study will monitor the drugs' pharmacokinetics separately to guide future dosing and safety considerations. During the trial, participants will be closely monitored from day 0 through day 56 for drug concentration levels and safety outcomes. Evaluations include blood tests for drug levels, immune response (antidrug antibodies), vital signs, and lab assessments. The study also tracks how the drugs are absorbed, distributed, metabolized, and eliminated. Participation involves several clinic visits for dosing and follow-up assessments, ensuring careful observation of the drugs' effects over nearly two months.

Researchers are investigating the use of 18F-DFA PET imaging to evaluate liver injury, a condition involving rapid liver function decline with symptoms like increased liver enzymes, jaundice, and abdominal discomfort. This observational study aims to assess how accurately this imaging method detects liver damage compared to standard clinical biochemical tests and liver biopsy, which is the current gold standard despite its sampling limitations. The study focuses on adults clinically diagnosed with liver damage or liver failure, exploring the correlation between 18F-DFA uptake in the liver and liver function indicators. Participants diagnosed with liver injury will undergo 18F-DFA PET imaging as part of the study. This radioactive tracer, based on vitamin C structure, is used to visualize liver function non-invasively. The imaging process involves a PET-CT scan lasting about 10 minutes, followed by a one-hour waiting period in the examination room before leaving. The study will compare imaging results with clinical liver function tests or liver biopsy findings to determine the sensitivity and specificity of this method. During the study, participants will have their liver function monitored using PET-CT scans and clinical biochemical markers. The primary outcomes include changes in liver uptake values on PET imaging at 6 months and the relationship between imaging results and standard liver function indicators. Participants will be followed up as needed, with assessments including liver enzyme levels and other blood tests. The total study duration depends on individual follow-up, and safety monitoring will address any issues related to PET imaging procedures.

Researchers are studying calderasib (MK-1084) to understand how its levels change over time in the body, focusing on both people with liver (hepatic) impairment and healthy volunteers. The study also aims to learn about the safety and tolerance of MK-1084 in those with liver impairment. This is a Phase 1 clinical trial sponsored by Merck Sharp & Dohme LLC. All participants will receive a single oral dose of calderasib on the first day of the study. The trial involves measuring calderasib levels at specific times up to about 7 days after dosing to analyze how the drug is processed in the body. Researchers will look at various pharmacokinetic measures such as drug concentration, clearance, and half-life. Participants will be closely monitored through blood sampling and assessments to measure drug levels and safety up to approximately 14 days after the dose. The study will record any adverse events and track whether participants discontinue due to side effects. Overall participation time and follow-up will cover up to two weeks after dosing, focusing on how the drug behaves and is tolerated in people with and without liver impairment.

Researchers are evaluating the effect of liver function impairment on how the drug HDM1002 behaves in the blood. The study focuses on adults aged 18 to 70, including those with normal liver function and varying degrees of liver impairment. This Phase 1 trial aims to understand the drug's pharmacokinetics, safety, and tolerability in these different groups. Participants receive a single dose of HDM1002 on the first day of the study. The study includes separate groups for people without hepatic impairment and those with mild, moderate, or severe hepatic impairment. Researchers compare how the drug is processed in the body across these groups. During the trial, blood samples will be collected at multiple time points up to 72 hours after dosing to measure drug concentration and binding in plasma. Safety and tolerability are monitored throughout. The study is randomized and open-label, with participation lasting through the sampling period. The trial is sponsored by Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Researchers are evaluating the behavior and safety of lepodisiran, a drug given as a subcutaneous injection, in adults with varying degrees of liver function, including normal, mild, moderate, and severe impairment. The study aims to understand how much lepodisiran enters the bloodstream and how long it stays in the body, as well as to observe any side effects in these groups. This is a Phase 1, open-label study conducted by Eli Lilly and Company. Participants will receive a single dose of lepodisiran injected under the skin. The study includes four groups based on liver function: one group with normal liver health and three groups with mild, moderate, or severe liver impairment, classified by Child-Pugh scores. The treatment is given once, and the study design is sequential without randomization or blinding. The study lasts up to about 9 weeks, excluding screening, during which participants will have their blood sampled to measure lepodisiran levels and monitor its clearance from the body. Researchers will assess pharmacokinetics, including the concentration of lepodisiran over time and its maximum concentration. Participants will also be monitored for safety and side effects throughout the study period.

Researchers are evaluating how nemtabrutinib, a drug given by mouth, behaves in the blood (pharmacokinetics) after a single dose in people with moderate liver impairment compared to healthy individuals. The study also aims to assess the safety and tolerability of nemtabrutinib in these participants. This is a Phase 1 clinical trial sponsored by Merck Sharp & Dohme LLC. Participants with moderate hepatic impairment and healthy matched controls each receive one oral dose of 25 mg nemtabrutinib on Day 1. The study groups include those with moderate liver impairment classified by specific medical criteria and healthy volunteers. Both groups receive the same dosage and form of the drug. Participants will have multiple blood samples taken before and at various times up to 336 hours after dosing to measure drug levels and related pharmacokinetic parameters. Safety is monitored through adverse event reports up to about 15 days. The total study duration includes dosing and follow-up assessments to evaluate how the drug is processed and tolerated in the body.

The purpose of this study is to assess how fast RAY1225 gets into the blood stream and how long it takes the body to remove it in participants with impaired liver function compared to healthy participants.

Researchers are evaluating the safety of siplizumab, an investigational anti-CD2 monoclonal antibody, as an induction immunosuppressive treatment in adult patients with autoimmune liver diseases (AILD) such as autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) undergoing liver transplantation. This pilot, open-label phase 1 study addresses the need for effective therapies to prevent immune-mediated graft injury and complications post-transplant. Siplizumab targets memory T cells involved in rejection and autoimmunity after liver transplantation in these patients. Participants will receive two intravenous doses of siplizumab at 0.6 mg/kg: one dose intraoperatively on the day of transplant (Day 0) and another on Day 4 post-transplant. Up to eight subjects will be enrolled. The study lasts about 15 months, including approximately three months waiting for transplant and 12 months of follow-up after transplantation. During the study, participants will be monitored for serious infections within the first month after transplant and for other outcomes such as immune-mediated liver injury, graft loss or death, rejection episodes, donor-specific antibodies, and disease recurrence over 12 months post-transplant. Assessments will include safety, tolerability, pharmacokinetics, and pharmacodynamics of siplizumab, with ongoing observation throughout the study period.

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.