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

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.

Fig. 1

Change in liver transaminase levels over time. Change in liver biochemistry over time. Box plots of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at 1 month (1 M), 3 months (3 M); 6 months (6 M), and 12 months (12 M). Boxes indicate the 25th to 75th percentiles, the line within the boxes marks the median, whiskers (error bars) above and below the box indicate the 90th and 10th percentiles, while P values are indicated within the graph.

Fig. 2

Change in surrogate markers of liver fibrosis and steatosis over time. Change in surrogate markers of liver fibrosis and steatosis over time. Box plots of nonalcoholic fatty liver disease fibrosis score (NAFLD), fibrosis-4 score (Fib-4), elastometry, and magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) at 6 months (6 M) and 12 months (12 M). Boxes indicate the 25th to 75th percentiles, the line within the boxes marks the median, whiskers (error bars) above and below the box indicate the 90th and 10th percentiles, while P values are indicated within the graph.

Fig. 3

Change in metabolic parameters over time. Change in metabolic parameters over time. a Oral glucose tolerance test (OGTT), plasma glucose at baseline and 30, 60, 90, 120 minutes (Min) after ingestion of 75 g of oral glucose. Data are expressed as median (IQR). Significance ( P  < 0.05) between curves was assessed by mixed model test (p values indicated within the graph). *Indicates a P  < 0.05. N = 11, nine of whom had type 2 diabetes. b , c , d Box plots of weight, glycated hemoglobin (HbA1c), and homeostatic model of insulin resistance (HOMA) at screening at 1 month (1 M), 3 months (3 M), 6 months (6 M), and 12 months (12 M). Boxes indicate the 25th to 75th percentiles, the line within the boxes marks the median, whiskers (error bars) above and below the box indicate the 90th and 10th percentiles, while P values are indicated within the graph.