Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients

Sponsor

Taipei Medical University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT04059029

Collaborator

(none)

200

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver biochemistry tests in the world. The prevalence rate of NAFLD has been reported to be 30-40% in men and 15-20% in women, up to 70% of people with type 2 diabetes mellitus (Type 2 DM) and even surpassing 74% to 90% of morbidly obese patients with body mass index (BMI) higher than 35 kg/m^2. The primary aims of this prospective cohort study would evaluate the predictive factors of successful weight reduction, NAFLD and nonalcoholic steatohepatitis (NASH) improvement in a large cohort of morbidly obese patients undergoing bariatric surgery. Secondarily, the diagnostic accuracy of noninvasive serum markers, doppler ultrasonography and transient elastography would be validated. Thirdly, we would conduct gene expression analyses to elucidate biological pathways underlying NAFLD phenotypes in this unique cohort.

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Fatty Liver Disease (NAFLD)	Procedure: Bariatric surgery

Detailed Description

This prospective study have been approved by Taipei Medical University-Joint Institutional Review Board. The starting point for each patient is the day of surgery and the end-point is 1 year after the operation. During bariatric surgery, all patients would undergo a liver biopsy under laparoscopic guidance. The diagnosis of NASH and liver fibrosis would be made histologically. For histological examinations, liver tissue specimens would be fixed in 10 % formalin, embedded in paraffin, and then stained with hematoxylin and eosin. A detailed history wound be obtained including history of alcohol use, type 2 DM, hypertension, or hyperlipidemia. Written informed consents would be obtained from all patients who would agree to undergo surgery. A histologic assessment would be planned approximately 1 year after bariatric surgery, if patient would agree.

In this study, excess weight loss (EWL) is defined as the excess weight over the ideal body weight calculated according to the Metropolitan Life Weight Tables. The weight reduction success would be defined as the percentage of excess weight loss (%EWL) >50% at the point of 1 year after operation. Diagnosis and classification of type 2 DM is based on criteria established by the American Diabetes Association. The individual components of glycemic control (levels of serum glucose, HbA1c levels) body weight, waist circumference, and blood pressure would be examined. Additionally, the levels of total cholesterol, LDL-C, triglyceride, uric acid, aspartate aminotransferase (AST),alanine aminotransferase (ALT), albumin, insulin, C-peptide, iron, calcium, complete blood cell counts would be assessed 1 day before surgery and 12 months post-operatively. All patients would receive abdominal ultrasonography, duplex doppler ultrasonography, transient elastography (FibroScan®) before and 12 months after bariatric surgery. The diagnosis accuracy of transient elastography (FibroScan®) would be validated. Transient elastography (FibroScan®) appears to be a non-invasive, reproducible, and reliable method for predicting liver fibrosis, in patients with hepatitis B virus, hepatitis C virus, NAFLD and alcoholic liver disease.

Patients body weight would be measured in light clothing without shoes to the nearest 0.1 kg, and body height would be measured to the nearest 0.1 cm. BMI is calculated as weight in kilograms divided by height in meters squared. Waist circumference would be measured midway between the lateral lower rib margin and the superior anterior iliac crest.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Predictors of Improvement of Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Bariatric Surgery

Actual Study Start Date :

Oct 1, 2016

Anticipated Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Morbidly obese patients with NAFLD Morbidly obese patient with Nonalcoholic fatty liver disease. The starting point for each patient is the day of surgery and the end-point is 1 year after the operation. During bariatric surgery, all patients would undergo a wedge liver biopsy under laparoscopic guidance. The diagnosis of NASH would be made histologically.	Procedure: Bariatric surgery During bariatric surgery, all patients would undergo a wedge liver biopsy under laparoscopic guidance.

Arm

Intervention/Treatment

Morbidly obese patients with NAFLD

Morbidly obese patient with Nonalcoholic fatty liver disease. The starting point for each patient is the day of surgery and the end-point is 1 year after the operation. During bariatric surgery, all patients would undergo a wedge liver biopsy under laparoscopic guidance. The diagnosis of NASH would be made histologically.

Procedure: Bariatric surgery

During bariatric surgery, all patients would undergo a wedge liver biopsy under laparoscopic guidance.

Outcome Measures

Primary Outcome Measures

Change from body mass index (BMI) at 12 months after surgery [pre-surgery and 12 months after surgery]
The BMI would be calculated by dividing the body weight (in kilograms) by the square body height (in meters).

Secondary Outcome Measures

Change from alanine aminotransferase at 12 months after surgery [pre-surgery and 12 months after surgery]
Liver function test
Change from aspartate aminotransferase at 12 months after surgery [pre-surgery and 12 months after surgery]
Liver function test
Nonalcoholic steatohepatitis [1 day of surgery]
The diagnosis of nonalcoholic steatohepatitis (NASH) would be made histologically. A score for steatosis, activity and fibrosis would be given to each patient for the diagnosis of NASH as in Bedossa's study. (Reference: Hepatology. 2012 Nov;56(5):1751-9.)

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult male and female Morbidly obese patients age 20-65 years with BMI over 37.5 kg/m^{2, or BMI over 32.5 kg/m}2 with comorbidity other than diabetes (hypertension, NASH, dyslipidemia, obstructive sleep apnea, osteoarthritis joint…etc.) or BMI over 27.5 kg/m^2 with poor control diabetes undergoing bariatric surgery

Exclusion Criteria:

The presence of end organ damage
Previous bariatric surgery
Women who are pregnant or nursing
Prolonged exposure to known hepatotoxins such as alcohol or drugs
Concurrent hepatitis B virus, hepatitis C virus, hepatitis D virus, or human immunodeficiency virus infection
Concurrent autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis
Wilson disease or hemochromatosis