Clinical trial NCT04059029: Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients
Official title: Predictors of Improvement of Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Bariatric Surgery
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
Keywords: Nonalcoholic fatty liver disease
morbidly obese
Bariatric surgery
Lead sponsor: Taipei Medical University Hospital
Sponsor class: OTHER
First posted: 2019-08-16
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Morbidly obese patient undergoing bariatric surgery

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from body mass index (BMI) at 12 months after surgery
timeFrame: pre-surgery and 12 months after surgery
Secondary outcomes:
measure: Change from alanine aminotransferase at 12 months after surgery
timeFrame: pre-surgery and 12 months after surgery
measure: Change from aspartate aminotransferase at 12 months after surgery
timeFrame: pre-surgery and 12 months after surgery
measure: Nonalcoholic steatohepatitis
timeFrame: 1 day of surgery
Other outcomes:
Locations:
Study officials:
affiliation: Comprehensive weight management center, Taipei Medical University hospital
name: Weu Wang, M.D.&PhD
role: STUDY_CHAIR
References:
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citation: Kao WY, Lin YF, Chang IW, Chen CL, Tang JH, Chang CC, Chang YJ, Wang W. Interleukin-2 receptor alpha as a biomarker for nonalcoholic fatty liver disease diagnosis. J Chin Med Assoc. 2021 Mar 1;84(3):261-266. doi: 10.1097/JCMA.0000000000000469.