Hepatic Effects of Gastric Bypass Surgery

Liver Diseases Clinical Trial

Official title:

Long Term Hepatic Effects of Gastric Bypass Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701376
• Other study ID #: 07-877
• Status: Completed
• Phase: N/A
• Start date: June 2008
• Est. completion date: September 2014

Study information

• Verified date: June 2020
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Liver disease in the morbidly obese is thought to occur due to the long-term presence of fat deposits in the liver, resulting in inflammation and scarring of the liver over time, which reduces liver function. However, many of these patients are unaware that their liver is damaged. There is currently no consensus regarding what the long-term effects of gastric bypass surgery are on pre-existing liver disease in morbidly obese patients. This study will determine the long-term effects on the liver after this type of surgical procedure.

Description:

Before or on the day of surgery liver function will be determined using the DDG-2001 Analyzer. This monitor is able to detect the concentration of a dye called indocyanine green dye (ICG) when present in the blood stream. A dose of 0.5 mg/kg of ICG will be injected into an IV in the arm. Over approximately fifteen minutes the DDG-2001 Analyzer will determine how quickly the liver removes the dye ICG from the blood stream. This value represents how well the liver is functioning. Blood samples are drawn before injection of ICG to measure liver function using standard liver function tests.

This same routine for injecting ICG and obtaining blood for routine liver function tests will happen one more time, after surgery, once the subject has lost a significant amount of the original weight (60% of excess weight). This amount of weight loss typically occurs between 12 to 18 months after gastric bypass surgery. This second ICG measurement will occur during an outpatient follow-up visit to CCF.

A biopsy will be taken from the liver during surgery. A second biopsy taken after the 60% weight loss will be compared to determine the effect of this surgery on the liver.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: September 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. BMI > 40.

2. Documented failed non-surgical treatment for morbid obesity.

3. Ability to undergo long-term follow-up after LGBS.

Exclusion Criteria:

1. BMI < 40.

2. Subject age < 18 years.

3. Inability to undergo long-term follow-up after LGBS (living distance > 300 miles).

4. Patients with known ESLD.

5. Patients found to have evidence of ESLD during preoperative evaluation for LGBS including portal hypertension, ascites, and coagulopathy.

6. Patients with known iodine sensitivity or allergy.

Related Conditions & MeSH terms

• Liver Diseases

Intervention

Other:
• liver biopsy
Subjects undergoing laparoscopic gastric surgery will be evaluated for liver function by comparing liver tissue biopsied during surgery with tissue biopsied after 60% weight loss

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aspartate Transaminase (AST) Change	To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure
Primary	Alanine Transaminase (ALT) Change	To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure
Primary	Alkaline Phosphate (ALK)	To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure
Primary	Total Bilirubin	To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure
Primary	Albumin	To assess the change in liver function from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)
Primary	Prothrombin Time (PT)	To assess the change in liver function from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)
Primary	Partial Thromboplastin Time (PTT)	To measure the change of PTT from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)
Primary	Indocyanine Green (ICG) K Value	To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure). ICG-k value is the slope of the decay curve of the serum ICG clearance graph, which is used to assess the liver function as it represents the rate of disappearance of ICG from blood as the liver exclusively distracts it. The lower k value means a lower rate of ICG clearance, indicating a worse liver function.	from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)
Primary	Number of Subjects of Nonalcoholic Steatohepatitis (NAS Steatosis)	To compare the distribution of NAS steatosis stage from before surgery to when patients lost 60% of their preoperative excess weight or weight loss had plateaued. The NAFLD activity score (NAS) from the NASH clinical Clinic Research Network is the unweighted sum of scores for steatosis, lobular inflammation, and ballooning hepatocyte degeneration, and ranges from zero to eight points. The histological reporting for grading steatosis was based on a scale of 0 to 3, with 0 being no steatosis (<5%), 1 being mild steatosis (involving 5-33% of the biopsy specimen), 2 being moderate steatosis (involving 34-66% of the specimen), and 3 being severe (involving >66%).	when patients lost 60% of their preoperative excess weight or weight loss had plateaued.
Primary	Number of Subjects of Nonalcoholic Steatohepatitis Lobular Inflammation	Lobular inflammation was similarly scored by number of foci per 200× magnification field (0 no foci: 1 < 2 foci: 2, 2-4 foci; 3, >4 foci) on biopsy specimen under microscope. This outcome was compared on its distribution before the surgery and once patients lost 60% of their preoperative excess weight or weight loss had plateaued.	when patients lost 60% of their preoperative excess weight or weight loss had plateaued.
Primary	Fibrosis	Fibrosis was measured from before surgery to after surgery once they lost 60% of their preoperative excess weight or weight loss had plateaued through biopsies	after surgery once they lost 60% of their preoperative excess weight or weight loss had plateaued
Primary	Nonalcoholic Steatohepatitis (NAS) Hepatocyte Balloon	Ballooning hepatocyte degeneration was scored as 0 (absent), 1 (few, difficult to identify), 2 (many, easily identified). This was to assess the change in the distribution of NAS hepatocyte ballon between before the surgery and once patients lost 60% of their preoperative excess weight or weight loss had plateaued	once patients lost 60% of their preoperative excess weight or weight loss had plateaued after surgery
Secondary	Diagnostic Accuracy-AST	AST was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery
Secondary	Diagnostic Accuracy-ALT	ALT was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate and the y-axis is the true positive rate. The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.	before RYGB surgery
Secondary	Diagnostic Accuracy-ALK	ALK was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate and the y-axis is the true positive rate. The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.	before RYGB surgery
Secondary	Diagnostic Accuracy-total Bilirubin	The total bilirubin was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.	before RYGB surgery
Secondary	Diagnostic Accuracy-PT	PT was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery
Secondary	Diagnostic Accuracy-PTT	PTT (Partial Thromboplastin Time) was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery
Secondary	Diagnostic Accuracy-ICG k Value	ICG k value was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery
Secondary	Diagnostic Accuracy-albumin	Albumin was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery
Secondary	Diagnostic Accuracy-multiple Factor	We also built a multivariable model using all preoperative liver function tests and ICG k clearance values to predict NASH (nonalcoholic steatohepatitis) from pre-RYGB values. AUC was used to assess the prediction performance of those multiple factors. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 95% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).	before RYGB surgery