Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Affecting approximately one-third of the United States (U.S.) population, the prevalence of NAFLD increases to 90% in patients with obesity. In 25% of patients, NAFLD progresses to a more severe form-non-alcoholic steatohepatitis (NASH)-which further increases the risks of cirrhosis and hepatocellular carcinoma. In 2017, the lifetime costs of caring for NASH patients in the U.S. were estimated at $222.6 billion, with the cost of caring for the advanced NASH (fibrosis stage ≥ 3) being $95.4 billion. It is projected that the number of NASH cases will increase by 63% from 2015 to 2030.~Liver biopsy (LB) remains the gold standard for diagnosing NASH. Although the presence of fibrosis is not required for diagnosis, fibrosis stage is the strongest predictor of liver-related outcomes, with stages 3 and 4 being associated with a mortality relative risk of 6.7 and 11.1, respectively, compared to no fibrosis. Traditionally, LB has been performed via a percutaneous or transjugular approach. With advancements in endoscopic ultrasound (EUS) technologies, EUS-guided LB (EUS-LB) has emerged as an alternative means, with a 90%-100% diagnostic yield and 0-0.9% adverse event (AE) rate.~In patients with advanced fibrosis, the main determinant of decompensation and mortality is the presence of portal hypertension (PH), defined as hepatic venous portal gradient (HVPG) > 5 mmHg. In 2017, Dr. Guadalupe Garcia-Tsao (Co-I) further subcategorized compensated cirrhosis into those with no PH (HVPG ≤ 5 mmHg), mild PH (HVPG > 5 but < 10 mmHg) and clinically significant PH (HVPG ≥ 10 mmHg) given the differences in their pathophysiological mechanisms, prognosis and potentially therapeutic approach.~Traditionally, HVPG is obtained by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP), which is used as a surrogate of portal venous pressure (PVP). In 2016, Dr. Marvin Ryou (Co-I) reported the safety and technical feasibility of measuring true PVP and HVP and thus directly assess portal pressure gradient (PPG) in pigs using a digital pressure wire delivered through an EUS-based needle. Since then, the technology has progressed with the current device consisting of an EUS-based needle connected to a digital compact manometer. Studies in humans now report 92%-100% technical success without AEs (compared to 7-9% AE rate for traditional LB).~The mainstay of treatment for NASH remains weight loss achieved via lifestyle modification (LM). Previous studies show a correlation between weight loss and improvement in histologic features of NASH with approximately 10% total weight loss (TWL) required for fibrosis regression. Nevertheless, the average weight loss associated with LM is 3.8%, with less than 10% of patients able to achieve the 10% TWL threshold, leaving the majority of NASH patients undertreated.~Endoscopic bariatric and metabolic therapy (EBMT) is an emerging field for the treatment of obesity. To date, four EBMT devices/procedures are approved by the Food and Drug Administration (FDA) and available: intragastric balloon (IGB), endoscopic sleeve gastroplasty via suturing (S-ESG), endoscopic sleeve gastroplasty via plication (P-ESG), also known as POSE, and aspiration therapy (AT).~P-ESG involves the use of an endoscopic plication device to reduce gastric volume. While P-ESG has been available in the U.S. for almost a decade, in 2017, Dr. Christopher Thompson (Co-I) invented a new plication pattern. Specifically, instead of placing plications primarily in the fundus, a novel P-ESG procedure, also known as distal POSE, involves placing plications in the gastric body, sparing the fundus. In addition to assisting with the first new P-ESG case in 2017, the PI, along with Dr. Thompson, has continued to refine the techniques to optimize efficiency, efficacy and generalizability. With the current technique, P-ESG appears reproducible and associated with a shorter learning curve compared to S-ESG. Furthermore, our study estimated a mean of 15% TWL, with all patients achieving ≥ 10% TWL without AEs at 6 months and a mean of 20% TWL at 12 months (see Preliminary Data).~Given the weight loss efficacy of EBMTs, it has been suggested that EBMTs may serve as a novel treatment category for NASH. Previously, the PI and Co-Is studied the effect of IGB-the oldest EBMT device-on NASH. EUS-LB performed at the time of IGB removal revealed resolution of all NASH histologic features including fibrosis. A follow-up study by a different group showed similar findings. Furthermore, studies have showed the benefits of S-ESG and AT on non-histologic features of NASH. Given the greater weight loss experienced after P-ESG compared to IGB (20% vs 10% TWL) and the more reproducible technique and shorter learning curve of the current P-ESG compared to S-ESG, we aim to assess the effect of P-ESG on NASH.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Affecting approximately one-third of the United States (U.S.) population, the prevalence of NAFLD increases to 90% in patients with obesity. In 25% of patients, NAFLD progresses to a more severe form-non-alcoholic steatohepatitis (NASH)-which further increases the risks of cirrhosis and hepatocellular carcinoma. In 2017, the lifetime costs of caring for NASH patients in the U.S. were estimated at $222.6 billion, with the cost of caring for the advanced NASH (fibrosis stage ≥ 3) being $95.4 billion. It is projected that the number of NASH cases will increase by 63% from 2015 to 2030. Given the weight loss efficacy of Endoscopic Bariatric and Metabolic Therapies (EBMTs), it has been suggested that EBMTs may serve as a novel treatment category for NASH. Previously, the PI and Co-Is studied the effect of Intragastric balloons (IGB)-the oldest EBMT device-on NASH. EUS liver biopsy performed at the time of IGB removal revealed resolution of all NASH histologic features including fibrosis. A follow-up study by a different group showed similar findings. Furthermore, studies have showed the benefits of S-ESG and Aspiration Therapy (AT) on non-histologic features of NASH. Given the greater weight loss experienced after P-ESG compared to IGB (20% vs 10% TWL) and the more reproducible technique and shorter learning curve of the current P-ESG compared to S-ESG, we aim to assess the effect of P-ESG on NASH.