Endoscopic sleeve gastroplasty an effective alternative therapy for MASH

Endoscopic sleeve gastroplasty (ESG) may be an effective alternative therapy in the treatment of patients with metabolic dysfunction-associated steatohepatitis (MASH), according to researchers from Spain. Subsequently, they said ESG should be used as part of second-line treatment, with or without other complementary weight loss therapies, especially in patients who do not respond to lifestyle modification.

The researchers conducted a prospective multi-centre, randomised, controlled, double-blinded clinical trial at four centres in Spain from April 2018 to December 2020. Patients were randomised 1:1 to ESG with the OverStitch system (Boston Scientific) plus lifestyle modification vs endoscopic simulated intervention (ESI) with a diagnostic upper endoscopy, which was called a sham endoscopy (SE) plus lifestyle modification.

The primary outcome was to assess the effectiveness of ESG plus lifestyle modification during 72 weeks vs standard of care in MASH resolution without worsening of fibrosis. MASH resolution was defined as the disappearance of ballooning and the disappearance or the persistence of minimal lobular inflammation (grade 0 or 1). Worsening of fibrosis is defined as the progression of at least one fibrosis stage.

In total, 40 patients were randomised, 20 in each group) group. Eighteen patients from the ESG group and 19 from the SE group completed the 72-week follow-up and underwent end-of-study liver biopsy. Men were 55% of the patients, with a median age of 56.5 years (interquartile range, 23–69 years). The mean BMI was 37.85 kg/m2. One-half of patients had type 2 diabetes, and 60% and 65% had a diagnosis of hypertension and dyslipidaemia, respectively.

A significant (p<0.05) reduction in body weight was observed in 94.4% of patients from the ESG group vs 57.9% in the SE group. TBWL was −9.47% (±9.38%) in the ESG group vs −3.91% (±5.43%) in the SE group (p<0.05). More than 10% of TBWL was achieved in 33.3% (6/18) of the ESG group vs 21.1% (4/19) in the SE group (p<0.05). More than 15% TBWL was achieved in 22.2% of patients in the ESG but none in the SE group (p<0.03). The greatest weight loss occurred in the first 12 weeks in both groups. The patients in the SE group gradually recovered their lost weight, whereas the patients in the ESG group maintained their weight loss until the end of follow-up (Figure 1). Waist perimeter reduction in the ESG group was −8.67 cm (±9.26 cm) vs −1.06 cm (±7.41 cm) in the SE group (p<0.012).

Figure 1: Time course of weight loss and abdominal perimeter.

Mean change in alanine aminotransferase (ALT) from baseline to week 72 in the ESG group was −27.67 U/L (±32.27 U/L) and for SE group was −13 U/L (±26.59 U/L) (p=0.146). Significant difference was observed between both groups in weeks 12 and 48. Mean change in aspartate aminotransferase (AST) from baseline to week 72 in the ESG group was −21.33 U/L (±26.02 U/L) and for the SE group was −12.22 U/L (±29.68 U/L) (p=0.334). There was no significant difference in AST changes throughout the follow-up. Significant improvement was also seen in gamma glutamyl transferase (GGT) changes at the end of follow-up in the ESG group (−41.22 U/L [±57.42 U/L]) vs the SE group (−4.06 U/L [± 38.75 U/L]) (p=0.037).

When comparing the pre- and postintervention biopsies separately, there were significant differences in the NAS score in both treatment groups. Patients that effectively achieved weight loss showed significant improvement in NAS score (−2.14 ± 2 vs −0.22 ± 1.48; p=0.012) in comparison with patients who did not. Losing more than 10% TBWL was also related to NAS score improvement (−4 ± 0.94 vs −0.81 ± 1.62; p<0.001). Moreover, steatosis, lobular inflammation and ballooning improved significantly when addressed separately. In addition, 70% of patients losing more than 10% achieved MASH resolution with no worsening of liver fibrosis vs 22.2% in patients with a TBWL lower than 10% (p=0.007).

“This is the first prospective multi-centre, sham-controlled, randomised trial to show how ESG plus lifestyle intervention was more effective in promoting weight loss than lifestyle changes and simulated upper endoscopy,” the authors concluded. “Weight loss leads to histologic improvement, with a significant reduction in the NAS score, as well as a significant decrease in liver stiffness by transient elastography. ESG is a safe endoscopic bariatric and metabolic therapy with very few adverse effects. Further studies are needed to confirm these findings and to better characterize its potential role in the management of patients with MASH.”

The findings were reported in the paper, ‘Endoscopic Sleeve Gastroplasty Plus Lifestyle Intervention in Patients With Metabolic Dysfunction-associated Steatohepatitis: A Multicenter, Sham-controlled, Randomized Trial’, published in the journal Clinical Gastroenterology and Hepatology. To access this paper, please click here