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Billeter, A.T.* ; Scheurlen, K.M.* ; Israel, B.* ; Straub, B.B.* ; Schirmacher, P.* ; Kopf, S.* ; Nawroth, P.P. ; Müller-Stich, B.P.*

Gastric bypass resolves metabolic dysfunction-associated fatty liver disease (MAFLD) in low-BMI patients: A prospective cohort study.

Ann. Surg. 276, 814-821 (2022)

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OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery. RESEARCH DESIGN METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent T2D, BMI of 25-35 kg/m2, glucagon-stimulated C-peptide of >1.5 ng/mL, HbA1c >7%, and age 18-70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies three years later. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a p-value <0.05 was defined as significant. RESULTS: MAFLD completely resolved in all patients three years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in HbA1c (8.45±0.27% to 7.09±0.26%, P=0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent anti-oxidative and mitochondrial genes. Additionally, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while denovo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably. CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-BMI patients with insulin-treated T2D with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

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