Active, not recruitingNot applicableInterventional
What this study is about
Diseases along the nonalcoholic fatty liver disease spectrum, which are tightly coupled to the obesity epidemic, are soon to become the commonest indication for liver transplantation in the United States. Bariatric surgery shows great promise in the treatment of these diseases. The studies proposed herein will be the first to measure in humans the relationships among (i) the liver's ability to burn fat and make glucose, two of its primary functions; (ii) the severity of nonalcoholic fatty liver disease; and (iii) the responses to bariatric surgery. These experiments will support deeper future mechanistic investigations of the metabolic mechanisms underlying nonalcoholic steatohepatitis (NASH) improvement with bariatric surgery. The premise of this study is that deranged hepatic mitochondrial metabolism is a key biomarker and mediator of the nonalcoholic fatty liver disease (NAFLD)/NASH continuum, and the central hypothesis the investigators will test is that preoperative hepatic fat oxidation and glucose production flux parameters differ between low versus high NAFLD activity score (NAS), and response of the liver to bariatric surgery can be predicted by preoperative fluxes.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age40 Years to 67 Years
SexAll
Healthy volunteersNot accepted
ConditionNASH - Nonalcoholic Steatohepatitis, NAS, Overweight or Obesity, Weight Loss, Bariatric Surgery Candidate
Full registry criteria
Inclusion Criteria: * Age 18 to 67 years at eligible visit * Diagnosed with NASH with a total NAS ≥ 3 including a ballooning score of at least 1, or non-NASH/NAFLD with a total NAS ≤3, or Diagnosed with T2DM or prediabetes, HbA1c\< 8% , or CAP score greater than or equal to 248 on Fibroscan * Body Mass Index (BMI) 30.0-55.0 kg/m2 at eligibility visit * Willingness to accept surgical intervention after an individual seminar session * All patients must have insurance with no exclusion for obesity related treatments or management of obesity surgery complications. This applies to all patients enrolled in the study * Expect to live or work within approximately three-hour traveling time from the study clinic for the duration of the one-year trial * Willingness to comply with the follow-up protocol and successful completion of the run-in * Written informed consent * Suitable for liver biopsy using the percutaneous approach * Vulnerable populations will not be targeted for inclusion, but those noted in section 9.1 may be allowed to participate provided they met all of the inclusion and none of the exclusion criteria. Exclusion Criteria: * Cardiovascular event (myocardial infarction, acute coronary syndrome, coronary artery angioplasty or bypass, stroke) in the past six months. * Current evidence of congestive heart failure, angina pectoris, or symptomatic peripheral vascular disease. * Cardiac stress test indicating that surgery or IMM would not be safe. * Pulmonary embolus or thrombophlebitis in the past six months * Cancer of any kind (except basal cell skin cancer or cancer in situ) unless documented to be disease-free for five years. * Significant anemia (hemoglobin 1.0 g/dL or more below normal range) or history of coagulopathy. * Serum creatinine \>1.5 mg/dL. * Serum total bilirubin greater than the upper limit of normal in the absence of Gilbert's syndrome, or alkaline phosphatase or ALT or AST greater than 2.5 the upper limit of normal. Elevated INR. * Alcohol intake more than one drink or \>20 grams per day * History of stomach surgery, bile duct surgery, pancreatic surgery, splenectomy, or colon resection. * Gastric or duodenal ulcer in the past six months. * History of intra-abdominal sepsis (except for uncomplicated appendicitis or diverticulitis more than six months prior to enrollment). * Previous organ transplantation. * Self-reported HIV-positive status, active tuberculosis, active malaria, chronic hepatitis B or C, or cirrhosis * Currently pregnant or nursing, or planning to become pregnant in the next two years. * History of alcohol, drug, or opioid dependency (excluding nicotine) in the past five years. * Active psychosocial or psychiatric problem that is likely to interfere with adherence to the protocol. * Depression A CESD score more than 17 and a psychologist determination that the patient is not a good fit for surgery. * Presence of any chronic or debilitating disease that would make adherence to the protocol difficult. * 12-lead EKG indicating that surgery would not be safe. * Serum c-peptide \<1.0 ng/ml post prandial. * Exclusions may also be made at the discretion of the attending physician or the eligibility committee. * Contraindication to MRI scanning. MRI contraindications are assessed by MR technologists on the day of scanning using a standard safety screening form. * History of endoscopy demonstrating esophagitis or Barretts changes in the esophagus. Any history of dysphagia. * Treatment with drugs associated with nonalcoholic fatty liver disease (amiodarone, methotrexate, oral glucocorticoids at doses greater than 5 mg/day, tamoxifen, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, valproic acid) for more than 4 weeks within the last 2 months prior to the initial screening. * Treatment with pioglitazone or high-dose vitamin E (\>400 IU/day) within the last 2 months prior to the initial screening.
