Condition 1: Nonalcoholic Steatohepatits (NASH). Condition 2: Obesity. Nonalcoholic steatohepatitis (NASH) Overweight and obesity
Conditions
Interventions
Intervention 1: Intervention group 1: Sleeve Gastrectomy - During laparoscopic SG, gastric resection starts within 3 to 6 cm of the pylorus along the greater curvature of stomach and ends with removal
Sponsors
Dr. Abidi Pharmaceuticals
CinnaGen
Digestive Disease Research Institute
Behbood Sanat Darman co
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Is a candidate for general anesthesia Is eligible for bariatric surgery (SG) Is =18 and =65 years old Have a BMI =30 and =45 kg/m2 Have a platelet count >150,000 and International Normalized Ratio (INR) =1.2 Have appropriate composite entry criteria on liver biopsy: NAFLD with activity score between 4 and 8, presence of hepatocyte ballooning, and fibrosis stage between 1 and 3, confirmed by independent reviews by 3 liver pathologists. In case of any discrepancies in histopathologic report, a joint review by 3 study pathologists will be performed. Have the ability and willingness to participate in the study and agree to any of the arms involved in the study. Able to understand the options and to comply with the requirements of each arm. Have a negative urine pregnancy test at screening and randomization visits for women of childbearing potential. Women, of childbearing age, must agree to use reliable method of contraception for 1 year. 11. Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication for at least 3 months prior to entry, with HbA1c =8.5%. ALT & AST > 35 in female and 45 in male
Exclusion criteria
Exclusion criteria: 1. Known history of other chronic liver diseases (drug induced, viral hepatitis, autoimmune, and genetic): a.Hepatitis B as detected by presence of hepatitis B surface antigen (HBsAg), b.Hepatitis C as detected by presence of hepatitis C virus (HCV) RNA, c.Autoimmune liver disease as diagnosed by antibodies and compatible liver histology, d.Primary biliary cirrhosis as defined by the presence of at least 2 criteria (elevated alkaline phosphatase, presence of anti-mitochondrial antibody, and histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts), e.Primary sclerosing cholangitis, f.Wilson’s disease as diagnosed by low ceruloplasmin and compatible liver histology, g.Alpha-1-antitrypsin deficiency as diagnosed by alpha1-antitrypsin level and liver histology, h.Hemochromatosis as diagnosed by presence of 3+ or 4+ stainable iron on liver biopsy, i.Drug-induced liver disease as diagnosed by medical history, j.Known bile duct obstruction, k.Suspected or proven liver cancer Type 1 diabetes or autoimmune diabetes Known cases of human immunodeficiency virus infection Prior bariatric surgery of any kind Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, splenectomy, biliary diversion, and trauma Thoracic, abdominal, pelvic and/or obstetric-gynecologic surgery within 6 months Any other surgery requiring general anesthesia within 6 weeks prior to signing the consent American Society of Anesthesiologists Class IV or V History of solid organ transplant Severe pulmonary disease defined as FEV1 180 mm Hg or diastolic blood pressure> 110 mm Hg) Chronic renal insufficiency with a eGFR is below 45 mL/min/1.73 m2, or being on dialysis Presence of moderate to severe GERD (Los Angeles classification B-D) Presence of moderate to large hiatal hernia (>3 cm) Presence of inflammatory bowel disease (Crohn’s disease or ulcerative colitis) Psychiatric disorders including dementia, active psychosis, severe depression requiring > 2 medications, history of suicide attempts, active alcohol or substance abuse within the previous 12 months Pregnancy Breastfeeding Diagnosis of malignancy within three years (except squamous cell and basal cell cancer of the skin) Anemia defined as hemoglobin less than 9 g/dL Any medical condition requiring anticoagulation therapy that cannot be temporarily discontinued for surgical procedure Known history of clotting disorders, including pulmonary embolus and deep vein thrombosis Use of any medications (prescription or over the counter), including herbal or other supplements for treatment of obesity or liver conditions (e.g. vitamin E or pioglitazone) during the last 3 months Use of investigational therapy or participation in any other clinical trial within 3 months prior to signing the consent History of pancreatitis (acute or chronic) or pancreatic carcinoma History of thyroid cancer Presence of concerning thyroid nodule Family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 Liver biopsies < 5 mm in length Absence of hepatocyte ballooning on liver biopsy Absence of fibrosis on liver biopsy NAFLD Activity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Liver Histopathology. Timepoint: before intervention and 12 months after intervention. Method of measurement: NAFLD activity score + hepatocellular ballooning + Fibrosis stage. | — |
Secondary
| Measure | Time frame |
|---|---|
| Liver Enzyme Activity. Timepoint: Before intervention and 6, 12 months after intervention. Method of measurement: Blood Test (ALT , AST , ALK.Phosphatase , Bilirubin).;Anthropometric changes. Timepoint: Before intervention and 1, 3, 6, 9, 12 months after intervention. Method of measurement: Waist Circumference + Weight and BMI.;Metabolic Changes. Timepoint: Before intervention and 12 months after intervention. Method of measurement: Lab Lipid Profile (Chol, LDL, HDL, TG) + Blood Pressure (sphygmomonometer) + Lab (BS, HbA1C, HOMA-IR) + CRP.;Quality of Life. Timepoint: Before intervention and 6, 12 months after intervention. Method of measurement: SF-36 questionnaire + chronic liver disease questionnaire (CLDQ) for NASH (CLDQ-NASH).;Complications. Timepoint: 1, 3, 6, 9, 12 months after intervention. Method of measurement: Complications specifically related to NASH disease, as well as complications of liver biopsy, liraglutide, empagliflozin, and SG will be recorded and evaluated through history taking and physical examination.;Liver stiffness. Timepoint: before intervention and 12 months after intervention. Method of measurement: Fibroscan Score. | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactDr Anahita Sadeghi
Tehran University of Medical Sciences
Outcome results
None listed