Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty

Background and Aims

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG.

Methods

One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis.

Results

Patients' mean body mass index was 40 ± 7 kg/m² at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02).

Conclusions

Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

Introduction

Given the high prevalence of obesity in the United States, its associated metabolic derangements, including non-alcoholic fatty liver disease (NAFLD), have become major public health concerns.¹ Various studies report that approximately a third of the U.S. population has NAFLD, including significant hepatic inflammation in the form of nonalcoholic steatohepatitis (NASH) as a precursor of advanced fibrosis in up to 5% of the population.^2,3 Visceral obesity is closely associated with insulin resistance (IR), one of the most important risk factors for NAFLD, and plays a major role in the development of hepatic steatosis and steatohepatitis.^4,5 IR leads to increased lipolysis, triglyceride synthesis, and increased hepatic uptake of fatty acids, resulting in hepatic lipid accumulation and steatosis.^6,7 Previous studies have shown improvement in hepatic steatosis and inflammation by agents that specifically target and enhance insulin sensitizers, such as the thiazolidinediones.⁸

Although there are several active clinical trials investigating a variety of drugs for the treatment of NAFLD, the efficacy of currently available treatment options, such as vitamin E, pioglitazone, semaglutide, or liraglutide, are limited.⁹ Therefore, weight loss remains the cornerstone of effective management of NAFLD. Previous studies have shown that the loss of at least 5% to 7% of total body weight is needed to achieve improvement in hepatic steatosis and steatohepatitis, respectively.^10,11 Although noninvasive treatments for obesity, including lifestyle interventions, have been shown to improve NAFLD (reflected in histologic improvement in hepatic inflammation and fibrosis) in the short term,^12,13 they rarely result in adequate and sustained weight loss.^14,15 Alternatively, bariatric surgery can be used to achieve significant and durable weight loss and improvement in IR for the management of NAFLD in patients with obesity.¹⁶ In addition to the improvement in IR in the setting of weight loss, malabsorptive bariatric procedures have been shown to be associated with early improvement in IR independent of weight loss.^17,18 Although multiple mechanisms such as lipid malabsorption and decreased incretin levels (eg, glucagon-like peptide 1 [GLP-1]) have been suggested, the exact mechanism of early and weight-independent improvement in IR after malabsorptive surgeries remains unclear.^19,20 Despite their significant beneficial effects, bariatric surgeries are associated with high morbidity and costs,²¹ and only a small percentage of qualifying patients with obesity actually undergo bariatric surgery.²²

The high prevalence of NAFLD and the aforementioned limitations of the available treatments have created a need for minimally invasive options to achieve adequate and sustainable weight loss for management of NAFLD in patients with obesity. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive bariatric procedure that is performed by endoscopic full-thickness suturing to decrease gastric volume and alter digestive physiology through the apposition of anterior and posterior walls of the stomach. Previous studies have shown the efficacy and safety of ESG to achieve substantial weight loss in patients with obesity.²³ Therefore, ESG could potentially be used to achieve weight loss and improve IR for treatment of hepatic steatosis and inflammation in patients with NAFLD. In a previous study, we have been able to show an improvement in hemoglobin A1c and alanine aminotransferase levels after ESG in patients with obesity.²³ However, to the best of our knowledge, the potential changes in IR and liver steatosis and fibrosis after ESG have not been studied to date. The aim of this study was to evaluate the effect of ESG on IR and changes in estimated hepatic steatosis and fibrosis in a cohort of patients with obesity and NAFLD.