Body Weight, Cirrhosis, HCC, Hepatitis C, Hepatocellular Carcinoma, Obesity, Weight Loss
Conditions
Keywords
bariatric surgery, minimally invasive, Embolization, ghrelin, gastric artery embolization
Brief summary
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
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.
Interventions
DEVICEEmbospheres Microspheres
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
Sponsors
St. Louis University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight | 12 months | Total body weight loss \> 10 % in 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical parameter-Blood pressure | 12 months | Improvement in blood pressure measured in mmHg |
| Laboratory parameter-Ghrelin and other serum obesity hormones(Leptin, GLP-1, PYY) | 12 months | Reduction in serum Ghrelin and other serum obesity hormones(Leptin, GLP-1, PYY) measured in pg/mL |
| Laboratory parameter-serum glucose | 12 months | Reduction in serum glucose levels measured as mg/dL |
| Laboratory parameters- HbA1c | 12 months | Reduction in HbA1c measures as percentage(%) |
| Clinical parameter- Abdominal circumference | 12 months | Improvement in abdominal circumference measured in centimeters (cm) |
| Number of patients with clinical adverse events | 12 months | Symptoms: pain, nausea, vomiting ;Adverse effects: Expected and unexpected |
| Number of patients with abnormal endoscopies | 12 months | Photos and clinical reports analyzed for ulcers |
| Eligibility for liver transplant | 12 months | 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. |
| Laboratory parameters-Lipid profile | 12 months | Improvement in lipid profile measured as mg/dL |
Countries
United States
Outcome results
None listed