Liver Failure

Participants and Location: This study will recruit up to 10 patients of at least 18 years of age with ascites due to diagnosed ovarian cancer. Eligible study patients will be screened and recruited at BC Cancer - Victoria. Paracentesis procedure and patient consent will occur at the Island Health - Royal Jubilee Hospital. Study Design: Participants meeting the inclusion criteria will be fitted with a continuous glucose monitor (FreeStyle Libre) before proceeding to their scheduled appointment for paracentesis. Labeled glucose will be administered via I.V. at dose of 8g of labeled glucose in 60 mL over 10 min. This is followed by 4g of labeled glucose in 30 mL over an hour. Sample collection and processing: During \[U-13C\]glucose infusions, the ascites specimens will kept on ice. Samples will be collected and analyzed by flow cytometry and mass spectrometry for states of metabolism and metabolite profiles respectively. The ascites fluid will be monitored for changes in metabolite levels. \[U-13C\]glucose Product Information: \[U-13C\]glucose clinical grade will be compound BC Cancer Pharmacy.

China suffers the heaviest burden of liver disease in the world. The number of chronic liver disease is more than 400 million. Either viral-related hepatitis, alcoholic hepatitis, or metabolic-related fatty hepatitis, etc. may progress to cirrhosis, which greatly threatens public health. Portal hypertension is a critical risk factor that correlates with clinical prognosis of patients with cirrhosis. According to the Consensus on clinical application of hepatic venous pressure gradient in China (2018), hepatic venous pressure gradient (HVPG) greater than 10,12,16,20 mmHg correspondingly predicts different outcomes of patients with cirrhosis portal hypertension. It is of great significance to establish a risk stratification system and perform tailored management for portal hypertension in cirrhosis. As a universal gold standard for diagnosing and monitoring portal hypertension, HVPG remains limitation for clinical application due to its invasiveness. How to construct a novel, non-invasive, accurate, and convenient method to achieve prediction of HVPG is an important general problem in the management of portal hypertension in cirrhosis. MR elastography allows for basic viscoelastic modeling of tissue, partitioning the complex shear modulus intoelastic components (eg, storage modulus) and viscous components (eg, lossmodulus and damping ratio \[DR\]). In previous studies, scholars have studied 2d MR elastography in cirrhosis to identify specific hepatic pathophysiologic interrelations. However, these mechanical properties of tissue measured with use of 3D MR elastography have yet to be investigated in cirrhosis to identify specific hepatic pathophysiologic interrelations. The investigators hypothesize that these mechanical properties might be valid presumptive surrogates of cirrhosis and portal hypertension, perhaps capable of supplanting liver biopsy or other invasive diagnostic interventions. This project aims to compare the ability of three demensional-magnetic resonance elastography (3D-MRE) to two demensional-magnetic resonance elastography (2D-MRE) to establish a risk stratification system and perform tailored management for portal hypertension in cirrhosis.

China suffers the heaviest burden of liver disease in the world. The number of chronic liver disease is more than 400 million. Either viral-related hepatitis, alcoholic hepatitis, or metabolic-related fatty hepatitis, etc. may progress to cirrhosis, which greatly threatens public health. Portal hypertension is a critical risk factor that correlates with clinical prognosis of patients with cirrhosis. According to the Consensus on clinical application of hepatic venous pressure gradient in China (2018), hepatic venous pressure gradient (HVPG) greater than 10,12,16,20 mmHg correspondingly predicts different outcomes of patients with cirrhosis portal hypertension. It is of great significance to establish a risk stratification system and perform tailored management for portal hypertension in cirrhosis. As a universal gold standard for diagnosing and monitoring portal hypertension, HVPG remains limitation for clinical application due to its invasiveness. How to construct a novel, non-invasive, accurate, and convenient method to achieve prediction of HVPG is an important general problem in the management of portal hypertension in cirrhosis and advanced chronic liver disease. Multiparametric three-dimensional (3D) MR elastography allows for basic viscoelastic modeling of tissue, partitioning the complex shear modulus into elastic components (eg, storage modulus) and viscous components (eg, loss modulus and damping ratio \[DR\]). However, these mechanical properties of tissue measured with use of 3D MR elastography have yet to be investigated in cirrhosis to identify specific hepatic pathophysiologic interrelations. We hypothesize that these mechanical properties might be valid presumptive surrogates of cirrhosis and portal hypertension, perhaps capable of supplanting liver biopsy or other invasive diagnostic interventions. This project aims to investigate the ability of three demensional-magnetic resonance elastography (3D-MRE) to establish a risk stratification system and perform tailored management for portal hypertension in cirrhosis and advanced chronic liver disease.

PD-1/PD-L1 inhibitors have achieved surprising results in lung cancer treatment and have been approved by the FDA for the treatment of different types of lung cancer. Their overall toxicity is lower than that of standard chemotherapy, but a number of immune-related adverse events have been reported clinically. Liver injury is one of the leading causes of death from adverse events due to PD-1/PD-L1 inhibitors. The occurrence of immune-related liver damage has an important impact on the tumor treatment and prognosis of patients. Most of the current domestic and international studies focus on the overall description and study of PD-1/PD-L1 antibody-related adverse events, and there is no definitive description of the risk factors for the development of immune-related liver injury in lung cancer patients. The aim of this project is to review the clinical data of lung cancer patients treated with PD-1/PD-L1 inhibitors from 2020.01 to 2024.06, to investigate the risk factors of PD-1/PD-L1 inhibitor-associated liver injury, to construct a prediction model for the occurrence of liver injury, and to take measures to prevent the occurrence of fatal immune liver injury, which is of great significance to the immunotherapy of clinical tumor patients. It is of great significance to the immunotherapy of clinical tumor patients.

This study adopts a prospective, single-center, open, single-arm, single-dose clinical design to evaluate the safety, tolerability, efficacy, immunogenicity, PD and PK characteristics of LY-M003 injection in WD patients, including the main study phase and the long-term follow-up study phase. This study is designed with 4 dose groups and 2 cohorts (adult cohort and pediatric cohort), namely: Dose Group 1 (1.0 × 10¹³ vg/kg), Dose Group 2 (2.0 × 10¹³ vg/kg), Dose Group 3 (4.0 × 10¹³ vg/kg) and Dose Group 4 (6.0 × 10¹³ vg/kg). Among them, Dose Group 1 serves as the starting dose of this study. The decision to escalate to the 4th dose group shall be made by the investigators and collaborators based on the accumulated safety, efficacy and other relevant data. Based on the accumulated efficacy and safety data of enrolled adult subjects, the investigator and collaborators will determine the starting dose, subsequent enrollment doses, and the number of enrolled cases for pediatric subjects.

DETECT-HCC-ESLD is a prospective multicenter study designed to examine early detection and risk stratification of hepatocellular carcinoma (HCC) in individuals with advanced liver disease. Adults with cirrhosis of different etiologies are enrolled and followed longitudinally with structured clinical assessments and imaging at predefined intervals. A key objective is to evaluate ultrasound and abbreviated MRI (AMRI) as surveillance modalities for HCC. The study examines detection performance, feasibility, and factors influencing image quality and interpretability. The protocol also includes the study of body composition, focusing on how variations in adiposity and muscle mass may relate to imaging characteristics, disease progression, and HCC risk. Longitudinal clinical and imaging data are used to explore prediction models aimed at identifying patients with differing levels of HCC risk. The study records outcomes such as incident HCC, liver-related complications, and mortality to support analyses of disease trajectories. The DETECT-HCC-ESLD study provides a structured framework for collecting clinical, imaging, and body composition data over time, enabling detailed evaluation of surveillance strategies and risk patterns in advanced liver disease.

Liver transplantation constitutes the only curative treatment for patients with end-stage liver disease. Advances in the field have led to favourable short- and medium term (1-3 year) post-transplant survival rates, but improvement in long-term survival rates remains disappointing. Due to the immunosuppressive therapy, a sedentary lifestyle and a poor recovery of post-transplant physical fitness, the proportion of liver transplant recipients that develop a new-onset or a deteriorating unfavourable cardiovascular risk profile is alarmingly high, and cardiovascular disease is the leading cause of death in this population. By consequence, in order to improve long-term outcome after liver transplantation, prevention of cardiovascular disease should be prioritized. The investigators are convinced that the challenge of cardiovascular disease and lack of physical fitness in liver transplant recipients should and can be addressed by subjecting these patients to a structured physical rehabilitation program. The aim of this project is implement a structured, individually-tailored, home-based but supervised physical rehabilitation and maintenance program for de novo liver transplantation recipients, and to demonstrate the feasibility and safety of such approach as well as its efficacy to improve physical fitness. The program will consist of a 2-phase intervention of i) home-based exercise training (aerobic exercise training as well as strength, flexibility and stability exercises under in-person and subsequently remote guidance) and ii) an 15-month maintenance phase of physical activity. This program will be studied in an open-label randomized trial where the regimen will be compared with a regimen of standard of posttransplant care. In addition to the interventional arm, two different regimens of exercise training intensity will also be studied.

This longitudinal, observational study aims to assess whether the characteristics of a novel blood peripheral biomarker can serve as indicators for depression and schizophrenia in patients at the Royal Columbian Hospital Psychiatric Clinics. The study will evaluate whether changes in these biomarker characteristics can help distinguish between depressed patients who do or do not respond to treatment and between individuals experiencing a single psychotic episode and those at risk of progressing to schizophrenia. To achieve this, blood samples and standardized mental health assessments will be collected across three study visits from up to 500 participants, grouped into two study arms based on their diagnosis: Depression (DEP) or Psychosis/Schizophrenia (PSY).

The goal of this clinical trial is to determine primarily whether a combinatorial therapy based on the administration of human albumin and enoxaparin is safe and effective in patients with decompensated cirrhosis discharged from the hospital. The main questions it aims to answer are: * Is this combinatorial therapy safe and tolerable? * Is this combinatorial therapy effective? * does this combinatorial therapy cost more or less than standard medical therapy? Participants will attend to study visits in which several test will be performed to asses disease evolution while they are taking study medication. Researchers will compare experimental group treated with combinatorial therapy plus standard treatment with control group treated with standard treatment to see if there are differences in the responses to the questions raised above.

There is an evolving crisis of chronic liver disease (CLD) in the UK and it is the only major chronic disease which is on the rise. The advanced stages of CLD, known as cirrhosis (a hardening and scarring of the liver), is the third biggest cause of death and loss of working life years behind heart disease and self-harm. People die from cirrhosis young with more than 1 in 10 in their 40s. Patients with cirrhosis are very susceptible to infections, antibiotics become ineffective and patients may become infected with 'super bugs'. There is an urgent need for antibiotic-free approaches. The body contains trillions of microscopic organisms called bacteria which play an important role in keeping us healthy. Many of these bacteria live within our bowel and help our immune system fight infection. There are increased numbers of 'unfriendly' bowel bacteria in patients with cirrhosis which emit substances that are harmful to health and disrupt the immune system. It could be beneficial to replace the unfriendly bowel bacteria in patients with cirrhosis with bacteria donated from a healthy person by performing a type of bowel bacteria transplant (known as faecal microbiota transplantation or FMT). The PROFIT trial was recently performed as a preliminary trial of FMT which was placed into the bowel with the help of a flexible camera (endoscopy). The study showed FMT was safe with no serious side effects, but patients told us they would prefer to take tablets rather than have an endoscopy. The chief investigator and her team have therefore made a capsule which contains dried stool from a healthy donor. Participants will need to take 5 of these capsules to achieve the same dose. The PROMISE clinical trial is to test whether treating patients with FMT capsules will reduce the likelihood of them getting an infection by measuring the time it takes to develop an infection resulting in hospital admission. This will be compared to a 'dummy' capsule that contains no FMT (placebo). Patients will be selected at random to have FMT treatment or placebo and both the study team and the patients will not know which treatment they are taking. Participants will need to take 5 capsules every 3-months. Participants will continue treatment for a total of 21-months or until they develop their first infection leading to hospital admission and will be followed-up for a maximum of 2-years. This study will also examine if having FMT will reduce the side effects of cirrhosis and if it has beneficial effects on the liver and immune system. The investigator team will study whether it reduces hospital admissions, the incidence of 'super-bug' infections and death. Laboratory studies will look at whether FMT treatment will help the immune system fight infection. The World Health Organisation describes the resistance of bacteria to the effects of antibiotics as one of the biggest threats to global health. The discovery of new antibiotics has not kept pace. The government's white paper proposes a 5-year plan to tackle resistance to antibiotics. Consultation with our patient co-applicant, patient advisory group, The British Liver Trust and Guts UK Charity have highlighted recurrent hospitalisation, over-use of antibiotics and fear of acquiring a 'super-bug' as being important priorities to patients. The results and study findings will be published in conjunction with patient support groups, the wider media and the NHS. The investigator will ensure the research impacts on the management of patients with CLD and shapes policy and guideline development.