CC BY-NC-ND 4.0 · Endosc Int Open 2021; 09(11): E1792-E1800
DOI: 10.1055/a-1550-7668
Original article

Endoscopic duodenal mucosal resurfacing for nonalcoholic steatohepatitis (NASH): a pilot study

Alia Hadefi
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Laurine Verset
3   Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
,
Martina Pezzullo
4   Department of Radiology. CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
,
Nicolas Rosewick
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Delphine Degré
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Thierry Gustot
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Christophe Moreno
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Jacques Devière
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
,
Eric Trépo
1   Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
2   Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
› Author Affiliations

Abstract

Background and study aims Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with limited treatment options. Duodenal mucosal resurfacing (DMR) has been associated with improvement in glycaemic parameters and liver function tests (LFTs) in type 2 diabetes. This study aimed to assess the effect of DMR in patients with NASH.

Patients and methods This was a single-center, open-label pilot study. Patients with definite, biopsy-proven NASH (nonalcoholic fatty liver disease activity score [NAS] ≥ 4) underwent a single DMR procedure followed by a 2-week postprocedural diet, without lifestyle intervention. The primary outcome was either resolution of NASH with no worsening of fibrosis or improvement in fibrosis (≥ 1 stage) with no worsening of NASH at 12 months. Secondary outcomes were changes in key histological parameters of NASH, surrogate markers of fibrosis, LFTs, and metabolic factors at 12 months.

Results From 2017 to 2019, 14 patients underwent successful DMR, of whom 11 were included in the analysis. After 12 months, no resolution of NASH was observed, while three patients (27 %) had marginal improvement in fibrosis with no worsening of NASH. Serious adverse events related to the procedure were reported in two patients out of 14 (14 %). Neither weight loss nor improvement in NAS score, or in the other secondary outcomes, were observed at 12 months.

Conclusions In this small and heterogenous study population, we found that DMR, in the absence of lifestyle intervention, did not induce NASH resolution and marginally improved liver fibrosis at 12 months.

Supplementary material



Publication History

Received: 26 April 2021

Accepted: 07 June 2021

Article published online:
12 November 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Younossi ZM, Golabi P, de Avila L. et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol 2019; 71: 793-801
  • 2 Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2020; Epub 2020 Dec 21
  • 3 Younossi ZM. Long-term outcomes of nonalcoholic fatty liver disease: from nonalcoholic steatohepatitis to nonalcoholic steatofibrosis. Clin Gastroenterol Hepatol 2017; 15: 1144-1147
  • 4 Eslam M, Newsome PN, Sarin SK. et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol 2020; 73: 202-209
  • 5 Davies MJ, D’Alessio DA, Fradkin J. et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41: 2669-2701
  • 6 Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L. et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015; 149: 367-378.e5
  • 7 Koutoukidis DA, Astbury NM, Tudor KE. et al. Association of weight loss interventions with changes in biomarkers of nonalcoholic fatty liver disease: a systematic review and meta-analysis. JAMA Intern Med 2019; 179: 1262
  • 8 Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017; 67: 829-846
  • 9 Lassailly G, Caiazzo R, Ntandja-Wandji LC. et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology 2020; 159: 1290-1301.e5
  • 10 Rajagopalan H, Cherrington AD, Thompson CC. et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study. Diabetes Care 2016; 39: 2254-2261
  • 11 Abu Dayyeh BK, Bazerbachi F, Graupera I. et al. Endoscopic bariatric and metabolic therapies for non-alcoholic fatty liver disease. J Hepatol 2019; 71: 1246-1248
  • 12 Van Baar ACG, Holleman F, Crenier L. et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: One year results from the first international, open-label, prospective, multicentre study. Gut 2020; 69: 295-303
  • 13 van Baar ACG, Beuers U, Wong K. et al. Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results. JHEP Reports 2019; 1: 429-437
  • 14 Haidry RJ, van Baar AC, Galvao Neto MP. et al. Duodenal mucosal resurfacing: proof-of-concept, procedural development, and initial implementation in the clinical setting. Gastrointest Endosc 2019; 90: 673-681.e2
  • 15 European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388-1402
  • 16 Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology 2019; 156: 1264-1281.e4
  • 17 Cui J, Philo L, Nguyen P. et al. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial. . J Hepatol 2016; 65: 369-376
  • 18 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
  • 19 Mingrone G, van Baar AC, Devière J. et al. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial. Gut 2021;
  • 20 van Baar ACG, Meiring S, Smeele P. et al. Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study. Gastrointest Endosc 2021; 94: 111-120.e3
  • 21 Eslam M, Sanyal AJ, George J. et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020; 158: 1999-2014.e1
  • 22 Chalasani N, Younossi Z, Lavine JE. et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67: 328-357
  • 23 Look AHEAD Research Group. Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes. N Engl J Med 2013; 369: 145-154
  • 24 Glass O, Filozof C, Noureddin M. et al. Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum. J Hepatol 2020; 73: 680-693
  • 25 Han MAT, Altayar O, Hamdeh S. et al. Rates of and factors associated with placebo response in trials of pharmacotherapies for nonalcoholic steatohepatitis: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2019; 17: 616-629.e26
  • 26 Rajagopalan H, Cherrington AD, Thompson CC. et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study. Diabetes Care 2016; 39: 2254-2261