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.

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 type 2 diabetes, body mass index of 25 to 35 kg/m², glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. 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 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (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 antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo 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-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

中文翻译：

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胃绕道手术解决低体重指数患者代谢功能障碍相关的脂肪肝 (MAFLD)：一项前瞻性队列研究

 客观的：

代谢功能障碍相关脂肪肝病（MAFLD）反映了代谢性疾病患者脂肪肝病的多因素发病机制。代谢手术对 MAFLD 的影响尚未得到研究。本研究在肥胖手术指南之外的典型队列中评估了 Roux-en-Y 胃绕道手术 (RYGB) 对 MAFLD 的影响。

 方法：

20 名患者参加了这项前瞻性单臂试验，研究 RYGB 对晚期代谢性疾病的影响 (DRKS00004605)。纳入标准为胰岛素依赖型 2 型糖尿病、体重指数为 25 至 35 kg/m ² 、胰高血糖素刺激的 C 肽为 >1.5 ng/mL、糖化血红蛋白为 >7%，年龄为 18 至 70 岁。进行了 RYGB，其中包括术中肝活检和 3 年后的随访肝活检。脂肪性肝炎由肝脏病理学家专家评估。使用 Wilcoxon 秩和检验分析数据， P值 <0.05 定义为显着。

 结果：

RYGB 后 3 年，所有患者的 MAFLD 完全消退，同时纤维化也得到改善。 55% 的患者停止胰岛素治疗，糖化血红蛋白显着降低（8.45±0.27% 至 7.09±0.26%， P =0.0014）。 RYGB 可能通过上调 NRF1 及其依赖性抗氧化和线粒体基因来降低全身和肝脏硝基酪氨酸水平。此外，随着胰岛素抵抗的改善，SIRT1和FOXO1等中枢代谢调节因子上调，同时脂肪从头生成减少，β-氧化得到改善。最后，胃肠激素和脂肪因子的分泌发生了有利的变化。

 结论：

RYGB 是一种很有前途的 MAFLD 治疗方法，即使对于接受胰岛素治疗的低体重指数 2 型糖尿病患者也能实现完全组织学缓解。 RYGB 恢复氧化平衡、脂肪组织功能和胃肠激素。