Bariatric Embolization of Arteries in Obese Patients With HCC to Allow Salvage Liver Transplantation

Study Overview
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Brief Summary
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Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and has a grave prognosis. Obesity is an epidemic in the US.Patients with HCC and obesity are not candidates for liver transplantation, depriving them of the best option for cure from HCC. Recent studies have shown that blocking blood vessels to a particular portion of the stomach (bariatric or left gastric artery embolization) can temporarily decrease levels of the appetite inducing hormone ghrelin, and result in weight loss.The purpose of this study is to determine if Left gastric artery embolization (LGAE) in patients with cirrhosis and HCC who are not transplant candidates due to morbid obesity, leads to clinically significant weight loss with eligibility for liver transplantation.

Detailed Description
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Obesity:In adults, obesity is defined as a BMI of greater than 30 kg/m2. It is estimated that, by the year 2030, 38% of the world's adult population will be overweight and another 20% obese .An expert panel convened by the NIH stated that for the first time in history, the steadily improving worldwide life expectancy could level off or even decline, as the result of increasing obesity. Liver cirrhosis with portal hypertension and HCC: The problem: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor seen in the setting of cirrhosis, which itself can be of varying etiology. NASH as cause for liver cirrhosis and HCC has been growing in last decade. Although Hepatitis C is currently the most common indication for liver transplant, longitudinal trends show that NASH has a trajectory to become the most common. Current options in management: Patients who develop HCC in the context of underlying chronic liver disease complicated by portal hypertension are not candidates for resection therapy; rather, orthotopic liver transplantation (OLT) offers the best option for cure and long-term survival. Most transplant centers have strict criteria for OLT; one of the most common is a BMI < 35 kg/m2. Most NASH patients with HCC will have a high BMI. Unfortunately in presence of HCC these patients have a very limited time to lose enough weight to qualify to be listed. Lifestyle modification and medical therapies are relatively ineffective. Bariatric surgery is contraindicated in patients with portal hypertension due to significant increase in post-operative mortality, more relevant in patient listed to liver transplantation. Thus a safe and effective minimally invasive option is needed. Based on currently available data, Left gastric artery embolization (LGAE) appears effective in inducing weight loss of about 10.5% in 3-6 months, with a high safety profile. In patients who have cirrhosis and portal hypertension with HCC and who are not transplant candidates due to morbid obesity , appropriate and timely weight loss of 10.5% in 3-6 months by performing LGAE may allow them to be listed and transplanted before their cirrhosis and tumor reaches an inoperable stage( within Milan criteria). In patients with HCC, the procedure can be performed concurrently with the procedure of Trans arterial chemoembolization which is commonly used in down staging HCC to Milan criteria.

Official Title
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A Single Center, Non-randomized Study to Evaluate the Safety and Efficacy of Left Gastric Artery Embolization in Obese Patients With Hepatocellular Carcinoma to Achieve Appropriate Weight Loss That May Allow Them to be Transplanted

Conditions
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Obesity, Weight Loss, Body Weight, Hepatocellular Carcinoma, HCC, Hepatitis C, Cirrhosis

Intervention / Treatment
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* Device: Embospheres Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, aged 18 years or older. Willing, able and mentally competent to provide written informed consent and willing to comply with all study procedures and be available for the duration of the study BMI >35 kg/m2 Adequate hematological, hepatic and renal function as follows: Hematological: Platelets > 50 x 109/L, INR <1.5 Hepatic : Total bilirubin <3 mg/dL Renal: Estimated GFR > 60ml/min.1.73m2 Clinical, laboratory and radiographic evidence (ultrasound/ CT/MRI) of cirrhosis of any etiology with portal hypertension and concomitant HCC (treated or untreated). Besides a BMI >35 kg/m2, otherwise eligible for liver transplantation Suitable for protocol therapy as determined by the interventional radiology Investigator. Exclusion Criteria: Pregnancy Active substance abuse Significant psychiatric problems, severe enough to cause suffering or a poor ability to function in life. Center for Epidemiological Studies Depression (CESD) score < 16. Significant alcohol consumption ( >20 g/day in women, >30 g/day in men) Weight > 400 lbs. Presence of systemic illness or other medical conditions relevant to survival .(Note that the presence of HCC will not be considered an exclusion criteria) Metastatic cancer Evidence of decompensated liver disease (uncontrolled ascites, or uncontrolled spontaneous encephalopathy) prior surgical weight loss procedures including gastroplasty, jejunoileal, or jejunocolic bypass, total parenteral nutrition within the past 6 months; Prior history of gastric pancreatic, hepatic, and/or splenic surgery Prior embolization to the stomach, spleen or liver. If review of available prior imaging studies (i.e. CT, MRI, or US) shows potential anatomical variations, presence of severe atheromatous disease, large arteriovenous shunting of blood. Abnormal Endoscopy - large sliding hiatal hernia or paraesophageal hernia, active peptic ulcer disease, active H. pylori infection History of abnormal Nuclear Gastric Motility examination-defined as delayed emptying of gastric contents > 90%, 60% and 10% at 1 hour, 2 hours, and 4 hours respectively. ASA Class 4 or 5 Child Pugh classification C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCC-Left gastric artery embolization<br>Embospheres Microspheres as artificial embolic agent for left gastric artery embolization | Device: Embospheres Microspheres<br>* Via a radial artery in the wrist or the femoral artery in the groin, arterial access will be obtained.Under live X-ray monitoring and using contrast, a catheter will be advanced into the artery of the stomach (left gastric artery). A CT scan will be performed on the X ray table to confirm the placement of catheter. Once this is confirmed small micro spherical particles (Embosphere Microspheres beads) will be injected though the catheter to occlude the artery and cut off blood supply to the stomach. Once the procedure is complete, in case of wrist access compression will be achieved with a band; in case of groin access a closure device will be used to plug the site of entry<br>* Other names: Bariatric embolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Total body weight loss > 10 % in 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical parameter- Abdominal circumference | Improvement in abdominal circumference measured in centimeters (cm) | 12 months | 
| Clinical parameter-Blood pressure | Improvement in blood pressure measured in mmHg | 12 months | 
| Laboratory parameter-Ghrelin and other serum obesity hormones(Leptin, GLP-1, PYY) | Reduction in serum Ghrelin and other serum obesity hormones(Leptin, GLP-1, PYY) measured in pg/mL | 12 months | 
| Laboratory parameter-serum glucose | Reduction in serum glucose levels measured as mg/dL | 12 months | 
| Laboratory parameters- HbA1c | Reduction in HbA1c measures as percentage(%) | 12 months | 
| Laboratory parameters-Lipid profile | Improvement in lipid profile measured as mg/dL | 12 months | 
| Number of patients with clinical adverse events | Symptoms: pain, nausea, vomiting ;Adverse effects: Expected and unexpected | 12 months | 
| Number of patients with abnormal endoscopies | Photos and clinical reports analyzed for ulcers | 12 months | 
| Eligibility for liver transplant | Weight loss to lower BMI< 35 kg/m2 to be eligible for transplant or receive a new liver transplant. Proportion of patients that achieved appropriate weight reduction to be listed for transplantation. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bariatric surgery, minimally invasive, Embolization, ghrelin, gastric artery embolization