Effects on Non-Alcoholic Steato-Hepatitis (NASH) liver disease, obesity-associated metabolic disturbances, weight loss, safety and quality of life in adults with NASH and obesity undergoing endoscopic sleeve gastroplasty.

EON (Endoscopic sleeve gastroplasty for Obesity complicated by NASH) Study is a feasibility study of endoscopic sleeve gastroplasty to evaluate the impact of this procedure on participants’ NASH liver disease and metabolic status. NASH is an increasingly prevalent cause of advanced liver disease, which is associated with the Metabolic syndrome and its risks of diabetes mellitus and cardiovascular disease. There is presently no medical therapy for NASH. While lifestyle intervention is the mainstay of management most patients do not achieve or maintain their dietary goals or weight loss. Bariatric surgery improves hepatic steatosis and liver tests. It also improves type 2 diabetes mellitus and may improve hepatic inflammation and fibrosis associated with NASH. Despite the increasing prevalence of obesity and the long-term benefits of bariatric surgery the incidence of procedures has plateaued since 2008; this may be because of the risk of surgical complications and the frequent need for hospital admission. Endoscopic surgery allows abdominal operations to be performed through the mouth, avoiding external incisions or scars. The endoscopic sleeve gastroplasty (ESG) procedure is an alternative to conventional surgical sleeve gastrectomy. ESG may lead to improvements in hepatic steatosis, inflammation and fibrosis, and in metabolic perturbations present in individuals who are obese and have NASH liver disease, with less complications than associated with conventional surgery. As part of the EON Study, endoscopic sleeve gastroplasty (ESG) will be performed using a technique described by Abu Dayyeh et al. (Abu Dayyeh BK, Acosta A, Camilleri M et al. Clinical Gastroenterology Hepatology 2016; dx.doi.org/10.1016/j.cgh.2015.12.030) Patients will receive intra-procedural sub cutaneous heparin (5000IU). A standard upper endoscope (GIF-H190; Olympus Australia, Notting Hill, VIC) will be used to examine the oesophagus and stomach for any anatomic contraindications. The procedure will be performed with the patient under general anaesthesia and with carbon dioxide insufflation. The procedure will be performed as a day-case procedure with participants being discharged home following recovery in the endoscopy recovery area. An oesophageal overtube will be placed, and then 3 parallel suture placement sites (anterior, greater curvature, and posterior) lines will be marked by using argon plasma coagulation starting at the incisura and extending proximally to the gastro-oesophageal junction. ESG will be created by using an interrupted triangular suture pattern that invaginates the greater curvature of the stomach to reduce the functional capacity of the stomach by 80%. A second layer of sutures will be placed over the length of the central sleeve in an interrupted pattern to further reduce the gastric volume and reinforce the sleeve. The sutures will be full thickness, enabled by a tissue screw that captures the muscularis propria, avoiding gastric wall delamination. The tissue screw is part of the EndoStitch endoscopic suturing device that will be attached to the endoscope (OverStitch endoscopic suturing system; Apollo Endosurgery, Austin, Texas, USA). Participants’ post-procedural diet will consist of liquid protein shakes for 4 weeks, then 2 weeks of a pureed diet before transitioning to a regular diet. The post-procedural diet will provide 70g of protein and 1000-1200 calories per day. Repeat upper endoscopy will be performed at 3 months to evaluate ESG durability. Before undergoing the study, intervention participants will undergo liver and metabolic evaluations, physical examination and psychological evaluation. Participants will undergo nutritional assessment and receive specific education on post-procedural diet with a clinical dietician. Following the intervention subjects will be followed up until week 48 end-of-study clinical evaluations. There will be clinical assessments at weeks 4, 12, 24 and 36 post-intervention. There will be questionnaires to screen for adverse events at weeks 4, 8, 12, 24 and 36. The end-of study evaluations will assess the impact of the intervention of participants’ liver, metabolic, nutritional status and quality of life. End-of study evaluations include liver biopsy, blood and urine tests, medical and dietician clinical assessments and a quality of life questionnaire. The ESG intervention will be performed by a specialist gastroenterologist with additional training and extensive expertise in interventional endoscopy. The procedure will be provided with the support of gastroenterology endoscopy nursing and specialist anaesthetist staff. Clinical assessments will be performed by a specialist gastroenterologist/ hepatologist, clinical dietician or nurse member of the investigating team. The procedure will take place in the Gastroenterology endoscopy unit at Lyell McEwin Hospital Adelaide. Clinical assessments and follow-up will take place in the Department of Gastroenterology & Hepatology, Department of Clinical Nutrition, Department of Endocrinology or Clinical Trials Unit at Lyell McEwin Hospital Adelaide.