Clinical Research Directory

Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis

This phase II trial studies how well simvastatin works in preventing liver cancer in patients with liver cirrhosis. Simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

The Efficacy of Aerobic Exercise Training on ANS and Endothelial Function in Compensated Cirrhosis

The goal of this randomized controlled trial is to investigate whether a 16-week structured aerobic exercise program combined with nutritional consultation can improve autonomic and endothelial function in patients with compensated cirrhosis. Study Design: This assessor-blinded, parallel-group randomized controlled trial will be conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Fifty adults with compensated (Child-Pugh class A) cirrhosis will be recruited during routine hepatology clinic visits. Eligible participants are aged 45-75 years, have a sedentary lifestyle (\<150 minutes of moderate or \<75 minutes of vigorous physical activity per week), and have abstained from alcohol for at least six months. Exclusion criteria include active or recently treated hepatocellular carcinoma (within three months), severe portal hypertension complications (untreated large varices, prior variceal bleeding, or severe gastropathy), transjugular intrahepatic portosystemic shunt (TIPS), unstable cardiac disease, orthopedic limitations, morbid obesity (BMI \>35 kg/m²), or current use of alpha- or beta-blockers that affect autonomic function. Intervention: Participants will be randomly assigned to either the intervention or control group. Both groups will receive nutritional consultation and individualized dietary guidance at baseline, week 8, and week 16. Nutritional goals are set at 35 kcal/kg/day and 1.2 g/kg/day of protein intake. If targets are unmet, the dietitian will provide individualized recommendations to support adequate intake. The intervention group will participate in a 16-week aerobic exercise program consisting of brisk walking at moderate intensity (50-70% of maximal heart rate), totaling 150 minutes per week. The program includes two phases: * Phase 1 (Weeks 1-4): Combined hospital-based (1 session per week) and home-based exercise under physical therapist supervision, with gradual intensity titration. * Phase 2 (Weeks 5-16): Fully home-based exercise following prescribed intensity and frequency, with weekly follow-up via telephone or messaging to monitor adherence, safety, and exercise log completion. The control group will maintain their usual physical activity levels while receiving the same schedule of nutritional consultations and weekly follow-up for monitoring compliance and adverse events. Outcomes: Primary outcomes include changes in autonomic and endothelial function after 16 weeks. * Autonomic function will be assessed using the Ewing autonomic battery test (HR response to standing, deep breathing, and Valsalva maneuver; BP response to posture and sustained handgrip) and heart rate variability (HRV) indices (SDNN, RMSSD, LF/HF ratio). * Endothelial function will be evaluated using flow-mediated dilation (FMD) of the brachial artery, analyzed via Cardiovascular Suite™ software to assess nitric oxide-dependent vasodilation. Secondary outcomes include: 1. Splanchnic hemodynamics: Changes in celiac and superior mesenteric artery (SMA) blood flow measured via mesenteric Doppler ultrasound (Vivid IQ, GE Healthcare). Time-averaged mean velocity (TAMV), vessel diameter, and blood flow will be recorded at baseline and post-intervention. 2. Sarcopenia-related measures: Muscle mass (DEXA, BIA), muscle strength (handgrip dynamometry), and physical performance (6-minute walk test). 3. Laboratory outcomes: Serum ammonia, liver function tests, fasting glucose, albumin, renal function, and coagulation profile. 4. Correlative analyses: Associations between (a) muscle mass and serum ammonia, and (b) muscle mass and autonomic parameters (e.g., HRV indices).

Effect of Laparoscopic Splenectomy on Renal Function in Cirrhotic Patients With Hypersplenism (2-Year Follow-Up)

Patients with liver cirrhosis often have impaired or at-risk kidney function due to the close link between liver and kidney (hepatorenal syndrome). Laparoscopic splenectomy is commonly used to treat splenomegaly and hypersplenism in these patients, but its impact on kidney function over 2 years is unclear. This study will follow patients undergoing laparoscopic splenectomy to measure changes in kidney function before and after surgery, identify risk factors for kidney damage and whether laparoscopic splenectomy can improve kidney function in the long term, and help improve care to protect kidney function in cirrhotic patients .

Timing of Endoscopic Intervention for Acute Variceal Hemorrhage: an RCT

Acute variceal upper gastrointestinal hemorrhage remains a hot potato in cirrhotic patients. The purpose of this study is to figure out whether urgent endoscopy (within 6h after gastroenterological consultation) is superior to non-urgent endoscopy (between 6h and 24h after gastroenterological consultation) in reducing rebleeding for these patients. This is a multi-centered, prospective, randomized, and controlled trial. 400 patients with suspected variceal bleeding will be randomized in a 1:1 ratio to receive endoscopic intervention either within 6h or 6-24h. Randomization is conducted by permuted block randomization stratified by age, systolic blood pressure (SBP), and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of acute variceal hemorrhage. This trial will provide valuable insights into the efficacy between the urgent endoscopy group and the non-urgent endoscopy group.

Microplastics, Cirrhosis and Portal Hypertension

Cirrhosis and portal hypertension are associated with an hyperdynamic circulation and hepatic inflammation, leading to complications like ascites, variceal bleeding, acute kidney injury, and higher infection risk. Microplastics (MPs) are a global plastic pollution issue, and studies have found plastic MPs or nanoparticles (NPs) contaminating human, animal and environmental ecosystems.It has been noted that the accumulation of MPs increases with a reduction in size of the plastic particle. MPs are categorized into primary particles such as manufactured plastics including pellets and cosmetic microbeads and secondary particles which originate from mechanical and ultraviolet disruption of large plastic particles. MPs can be ingested via food or beverages, especially plastic packaged comestibles or inhaled as environmental pollutants. Contamination of medications such as antibiotics, intravenous fluids, albumin and medical devices is another source of exposure to microplastics in patients with chronic liver disease (CLD)In particular exposure to endoscopic interventions, liver biopsy, and invasive procedures such as paracentesis and interventional radiology procedures can lead to plastic exposure and deposition of MPs in the liver and other tissues in patients with cirrhosis. It may be hypothesized that these may contribute to hepatic inflammation and progression of cirrhosis and portal hypertension. Globally, there is new research on the influence of MPs on the environment, plant and animal ecosystems and human health. Polystyrene (PS) microspheres that concentrate in the liver, intestine and the kidneys of mammals disrupt lipid and energy metabolism, impair mucus secretion, and alter the microbiome. Therefore, studies are required to assess how and to what extent, MPs impact human health, and affect chronic diseases like cirrhosis and reduce longevity. The study investigators will assess the presence of MPs in the liver, kidneys and intestine of patients with liver cirrhosis and compare it with those without underlying liver disease and determine the impact on portal hypertension and fibrosis, and cardiovascular and metabolic function.

DICE Study- Diastolic Improvement With Carvedilol & Empagliflozin in Patients With Cirrhosis

1. This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis. 2. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated. 3. Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.

Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease

The purpose of this research study is to test the safety, tolerability, and effectiveness of the capsules that contain bacteria from healthy individuals when used to treat alcohol craving and drinking.

Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant

Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.

Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS

TIPS has been used for 20 years, as a means of reducing portal pressure in patients with cirrhosis and portal hypertension related complications. TIPS proved more effective than alternative treatments in controlling or preventing variceal bleeding and refractory ascites. The main drawback of the TIPS procedure is progressive overt hepatic encephalopathy (OHE). Three risk factors for post-TIPS OHE have been identified: age over 65 years, history of previous episodes of OHE, and Child-Pugh score equal to or over 10. However, the incidence of post-TIPS OHE in patients fulfilling these criteria remains close to 35 %.

Evaluation of the Strip PeriScreen for the Fast Diagnosis of the Spontaneous Infection of the Liquid of Ascites During the Cirrhosis

The forecast of the spontaneous infection of the liquid of ascites (ISLA) at the cirrhotic patient is still burdened by a heavy mortality. The fast diagnosis of the ISLA is thus an essential stake to improve the forecast. Investigators would so like to estimate the interest of the strip PeriScreen for the fast diagnosis of the ISLA at cirrhotic patients . Investigators plan to include 670 patients, what would allow to make out a will at least on ascites 2000 on about twenty centers for duration estimated of 12 months.

Comparison of Angiotensin II to Standard Dose Vasopressors on Change in Arterial Elastance

A study to see whether a medication called Angiotensin II works better than the routinely used medication to raise blood pressure in people with liver disease who are experiencing a serious drop in blood pressure. The investigators want to find out if Angiotensin II can help the heart and blood vessels work together more effectively than standard treatments.

Extracellular RNA Markers of Liver Disease and Cancer

The study will examine and evaluate the use of extracellular RNA in blood as markers for the diagnosis of liver disease or cancer, and as markers for prediction of response to treatment or recurrence of cancer after surgery

The Impact of Liver Cirrhosis on Outcomes in Trauma Patients

Given that there are only a few studies on the effects of cirrhosis on trauma patients and none have addressed the impact cirrhosis has on the incidence of infections, it is important that we study this to determine the mortality in cirrhotic trauma patients and ascertain the incidence of infectious complications in these patients. We hypothesize that trauma patients with cirrhosis will have higher rates of mortality and infectious complications.

Muscle Mass Via UltraSound in Cirrhosis (MMUSCLE)

The goal of this observational cohort study is to learn about loss of muscle mass and muscle strength (sarcopenia) in patients with cirrhosis. The main question\[s\] it aims to answer are: * what is the prevalence and development of sarcopenia in cirrhosis? * what is the role of malnutrition? Participants will * undergo a muscle ultrasound of the lower and upper limb muscles * handgrip strength will be measured * malnutrition screening and assessment * complete a questionnaire to assess quality of life

Radiation Therapy in Treating Patients With Hepatocellular Carcinoma, Cholangiocarcinoma, or Liver Metastasis Who Have Impaired Liver Function

This phase I trial studies the side effects and the best dose of radiation therapy in treating patients with hepatocellular carcinoma, cholangiocarcinoma, or cancer that has spread from the original (primary) tumor to the liver who also have impaired liver function (liver damage caused by cirrhosis, chemotherapy, or surgery). Radiation therapy (RT) uses high energy x-rays to kill tumor cells and shrink tumors. New methods of giving RT to the liver may help control cancer.

Bumetanide vs. Furosemide in Cirrhosis

Patients with cirrhosis are frequently hospitalized due to an acute decompensation of their liver disease including bleeding, jaundice, encephalopathy, and volume overload. Volume overload is associated with increased mortality from acute hypoxic respiratory failure, hemorrhage from esophageal varices, and spontaneous bacterial peritonitis. Clinical practice guidelines describe sodium restriction and diuretics as first-line treatment, combined with regular body weight monitoring to assess response. In patients with suboptimal response to furosemide, alternative loop diuretics like torsemide or bumetanide may improve natriuresis. Bumetanide has a theoretic advantage over furosemide due to its more rapid and complete intestinal absorption, combined with a prolonged half-life in patients with hepatic dysfunction. In this pragmatic study, the aim is to compare the efficacy of diuresis with bumetanide versus furosemide among hospitalized patients with cirrhosis.

Deciphering the Mechanisms Involved in Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis

Background: \- Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen. Objectives: \- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen. Eligibility: \- People over age 18 with HCV and clinically stable liver disease. Design: * Participants will be screened with medical history and physical exam. They will have blood tests and imaging studies. * Participants will have 2 outpatient visits and a 3-day stay at the clinic. * At visit 1, participants will have urine and blood tests. They will have a magnetic resonance imaging (MRI) scan. A solution will be injected into a vein. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that slides in and out of the cylinder. * At visit 2, a substance will be injected into a vein and swallowed. Participants will then have blood drawn 5 times over 90 minutes. * During the inpatient stay, serial blood tests will be drawn. * Participants will give 2 stool samples and have another MRI. * A needle will be inserted through the chest wall into a vein inside the liver, guided by ultrasound. The blood pressure inside this vein will be measured and blood will be drawn from it. About 1 inch of liver tissue will be removed. * A study investigator will call participants to discuss all test results.

PSYLIVER-PILOTE: Involvement of the Autonomic Nervous System in Hepatocellular Carcinoma (HCC)

Chronic liver diseases affect 1.5 billion people worldwide and can lead to cirrhosis and hepatocellular carcinoma (HCC), which ranks as the third leading cause of cancer-related mortality globally. Despite advances in the treatment of hepatitis B and C, metabolic diseases, and addiction, HCC incidence continues to rise. In France, between 2010 and 2015, the five-year survival rate for liver cancer (90% of which is HCC) was 18% for men and 19% for women. Treatment of HCC is based on the BCLC classification (Barcelona Clinic Liver Cancer), which evaluates both cancer progression and liver function (Child-Pugh classification). Patients at early stages (0 or A) have a survival rate of over 5 years, while those at more advanced stages (C or D) have significantly lower survival rates, highlighting the importance of better early detection tools. Current screening for HCC in cirrhotic patients involves biannual US-scan. However, ultrasound sensitivity for detecting tumors smaller than 2 cm is around 25%. Therefore, developing personalized strategies to predict and detect early-stage HCC is crucial to improving patient outcomes. Various clinical and biological scores have been developed to assess the risk of developing HCC in cirrhotic patients, but these scores remain imperfect. Molecular heterogeneity in HCC, as revealed by transcriptomic studies, could explain the variability in outcomes and treatment responses. This heterogeneity in occurrence, phenotype, and progression of HCC suggests individual singularities that are not yet well understood. These individual singularities are likely linked to the autonomic nervous system (ANS), particularly in the central nervous system (CNS), which regulates various physiological processes. The ANS consists of the sympathetic nervous system (SNS), mainly adrenergic, and the parasympathetic nervous system (PNS), mainly cholinergic. These two systems function antagonistically but with different temporal dynamics. A better understanding of the interaction between tumor cells and their environment through the ANS could lead to the identification of new biomarkers to predict HCC development and therapeutic targets. The role of the ANS in cancer development has been explored in various cancers, including prostate, stomach, pancreatic, breast, and ovarian cancers, where the ANS regulates inflammation and immune responses. In chronic liver diseases, the liver is innervated by both sympathetic and parasympathetic fibers, and this innervation plays a role in regulating metabolism, liver regeneration, and fibrosis progression. Chronic liver disease etiologies, such as alcohol consumption, metabolic syndrome, and viral hepatitis, disrupt the balance between the SNS and PNS, contributing to liver dysfunction. The severity of liver damage is linked to autonomic dysfunction, and heart rate variability, a marker of PNS activity, is correlated with survival in patients with terminal-stage HCC. Our recent research has shown that patients with HCC exhibit a reconfiguration of the intrahepatic ANS, with a consistent cholinergic orientation at the neuro-hepatic synapse. Patients with parasympathetic orientation (as compared to sympathetic orientation) have more aggressive tumors, shorter survival, and, from a pharmacological perspective, anticholinergics increase sensitivity to targeted HCC therapies. Tumor cells and cytotoxic lymphocytes are most strongly associated with cholinergic receptor enrichment and depletion, respectively. In this context, the PSYLIVER-PILOTE study builds on these findings by investigating the involvement of the ANS in HCC through non-invasive extra-hepatic measures. The SNS and PNS are connected to brain regions involved in cognitive, emotional, and social information processing, such as the anterior cingulate cortex, insula, ventromedial prefrontal cortex, amygdala, and hypothalamus. These brain areas are involved in cognitive control and emotional processing. Additionally, experimental data from polyvagal theory and neurovisceral integration theory highlight the role of the ANS in regulating cognitive, emotional, and social processes, as well as psycho-behavioral traits. For instance, confronting a person with cognitive tasks and emotional or social information alters the balance of sympathetic and parasympathetic activity. Similar changes are observed in psycho-behavioral disorders like depression, emotional dysregulation, stress, and aggression. Thus, the PSYLIVER-PILOTE study aims to identify extra-hepatic markers of ANS activity associated with HCC, analyzing both electrophysiological indices (from the peripheral nervous system) and psycho-behavioral indices (from the central nervous system). This project could open new avenues for early HCC detection and the development of personalized treatments

Intravenous Ciprofloxacin Versus Intravenous Ceftriaxone: Spontaneous Bacterial Peritonitis in Cirrhosis of Liver

Spontaneous bacterial peritonitis (SBP) is one of the leading causes of morbidity and mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common bacterial infection in patients with cirrhosis and ascites, occurring in 10 to 30% of patients, with in-hospital mortality rates ranging from 20 to 30%1. Early diagnosis and a prompt antibiotic therapy have considerably decreased the mortality rate associated with an episode of SBP from 80% to approximately 20- 30% in the last decade. It is secondary to impaired humoral and cellular immune responses that results in indirect intestinal bacterial translocation into the ascitic fluid 2,3. The incidence of spontaneous bacterial peritonitis in hospitalised patients with cirrhosis varies from 7-23% in the West. It is around 33% in Pakistan. Translocation of bacteria (mostly gram negative) from the intestinal lumen due to decreased phagocytic activity of macrophages and increased intestinal permeability in cirrhotic patients is an important step in the development of spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is also associated with a poor long-term prognosis for patients, as mortality rates can reach 50 to 70% at 1 year

A Randomized Controlled Study Evaluating Bariatric Surgery as a Treatment for Severe NASH With Advanced Liver Fibrosis in Non-severe Obese Patients

The aim of the study is to demonstrate the superiority of bariatric surgery on the disappearance of NASH without worsening of fibrosis in comparison to medical standard treatment in obese patients (35 kg/m² \> BMI ≥ 30 kg/m²) with NASH complicated of advanced fibrosis (F3 and F4 fibrosis grade according to Brunt score).

Preventing Liver Cancer Mortality Through Imaging With Ultrasound vs. MRI

The study is a randomized trial of two different screening methods for early detection of liver cancer in patients with cirrhosis of the liver. The goal of PREMIUM is to compare an abbreviated version of the diagnostic gold standard for HCC (aMRI) +AFP to the standard-of-care screening (US+AFP) in patients at high risk of developing HCC. The investigators hypothesize that HCC will be detected at earlier stages, allowing for more curative treatments and resulting in a reduction in HCC-related mortality.

EUS vs TJ for Liver Biopsy and Portal Pressure Gradient Measurement

This study will directly compare the endoscopic ultrasound guided approach to obtain adequate liver biopsies and portal pressure gradient measurements to the current standard of care which uses the transjugular approach.

Evaluation of Minimal Hepatic Encephalopathy in Patients With Cirrhosis and Portal Hypertension

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment and represents the mildest type of hepatic encephalopathy (HE). Portal hypertension is the main complication of cirrhosis and is responsible of severe complications such as HE. The consequence of portal hypertension is the formation of the spontaneous portosystemic shunts (SPSS). The relationship between the SPSS and their characteristics and the prevalence of MHE in patient with cirrhosis is poorly known. The main objective of this study is to evaluate the MHE in patients with cirrhosis and portal hypertension.

Apixaban-PK Trial: Preventing Portal Hypertension Complications in Cirrhosis

The APIXABAN-PK trial is a prospective, randomized, single-blind, placebo-controlled study designed to evaluate the efficacy and safety of apixaban in combination with carvedilol versus placebo with carvedilol in preventing portal hypertension-related complications in patients with cirrhosis. Conducted at the Gastroenterology and Hepatology Department and Clinical Trials Unit (CTU) of Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan, the trial will enroll eligible cirrhotic patients with portal hypertension. Participants will be followed for 12 months to monitor hepatic decompensation events, variceal bleeding, portal vein thrombosis, and mortality, while safety and tolerability of apixaban will be closely assessed. This study aims to provide local evidence for apixaban use in cirrhosis management in Pakistan.