EFFECT OF ENDOSCOPIC GASTRIC REMODELING ON HISTOLOGIC METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) AND LIVER FIBROSIS: A 12-MONTH PROSPECTIVE OBSERVATIONAL STUDY

Background:
Metabolic dysfunction-associated steatohepatitis (MASH) is traditionally treated with lifestyle modification. Nevertheless, most patients are unable to achieve the 10% total weight loss (TWL) threshold required for fibrosis regression. Endoscopic gastric remodeling (EGR) is an effective weight loss procedure. This study aims to assess the effect of EGR on histologic features of MASH and portal pressure.

Methods:
This was a 12-month prospective study. Inclusion criteria were obesity and biopsy-proven MASH with at least stage 1 fibrosis. Exclusion criteria included decompensated cirrhosis. Subjects underwent EGR using an endoscopic plication device to reduce the gastric volume. Single-session endoscopic ultrasound-guided liver biopsies (EUS-LB) and endoscopic ultrasound-guided portosystemic pressure gradient measurements (EUS-PPG) were performed before and 12 months following EGR. Liver histology was assessed using the NASH CRN classification. The primary outcome was the efficacy of EGR in treating MASH with liver fibrosis assessed using FDA standards. This included the proportion of subjects who experienced 1) an improvement in liver fibrosis by at least one stage without worsening of MASH or 2) a resolution of MASH without worsening of liver fibrosis at 12 months. Secondary outcomes included changes in NAFLD activity score (NAS), non-invasive tests (NITs) for fibrosis and steatosis, and PPG at 12 months compared to baseline. Additionally, weight loss efficacy and safety were assessed. ClinicalTrials.gov Identifier: NCT04820036

Results:
49 subjects were screened and underwent EUS-LB and EUS-PPG prior to EGR. Of these, 29 were excluded, and 20 subjects were enrolled in the study. Mean age and BMI were 50±15 years and 43.8±12.0 kg/m². 13/20 subjects (65%) had pre-diabetes or diabetes. Of the 20 subjects, 12 were eligible for a one-year post-EGR follow-up, ten of whom underwent a repeat EUS-LB and EUS-PPG (83% follow-up rate) (Figure 1). Primary Outcomes: At 12 months, 4 of 10 subjects (40%) experienced an improvement in liver fibrosis by at least one stage without worsening MASH. Six of 10 subjects (60%) achieved MASH resolution without worsening of liver fibrosis (Figure 2). Secondary Outcomes: NAS improvement was achieved in 8/10 (80%) subjects. PPG decreased from 2.7 to 1 mmHg (p=0.002). There were significant improvements in NITs for fibrosis, including liver stiffness measurement on transient elastography, ALT and NFS, and NIT for steatosis, including the controlled attenuation parameter, and hemoglobin A1c (Figure 2). Weight loss at 12 months following EGR was 15.9±8.2% TWL, with 69% achieving ≥10% TWL. There were no severe adverse events following EGR, EUS-LB or EUS-PPG.

Conclusion:
EGR improves clinical, histological and metabolic features of MASH and should be considered a viable alternative in the care of these patients.