Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Ann Surg. 2022 Nov 1;276(5):814-821. doi: 10.1097/SLA.0000000000005631. Epub 2022 Jul 26.
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.
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/m 2 , 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.
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.
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.
代谢相关脂肪性肝病（MAFLD）反映了代谢性疾病患者脂肪肝的多因素发病机制。代谢手术对 MAFLD 的影响尚未得到研究。本研究评估了 Roux-en-Y 胃旁路术（RYGB）在肥胖手术指南之外的典型队列中对 MAFLD 的影响。
本前瞻性、单臂试验纳入了 20 例接受 RYGB 治疗的先进代谢性疾病患者（DRKS00004605）。纳入标准为胰岛素依赖性 2 型糖尿病、体重指数 25 至 35kg/m2、胰高血糖素刺激 C 肽>1.5ng/mL、糖化血红蛋白>7%和年龄 18 至 70 岁。进行了 RYGB 手术，术中进行肝活检，并在 3 年后进行随访肝活检。由经验丰富的肝脏病理学家评估脂肪性肝炎。使用 Wilcoxon 秩和检验对数据进行分析，P 值<0.05 定义为差异有统计学意义。
所有患者在 RYGB 术后 3 年 MAFLD 完全缓解，纤维化也得到改善。55%的患者停用胰岛素治疗，糖化血红蛋白显著降低（8.45±0.27%至 7.09±0.26%，P=0.0014）。RYGB 通过上调 NRF1 及其依赖的抗氧化和线粒体基因，降低了系统和肝脏的硝基酪氨酸水平。此外，中央代谢调节剂如 SIRT1 和 FOXO1 上调，同时新生脂肪生成减少，β-氧化改善，胰岛素抵抗得到改善。最后，胃肠道激素和脂肪因子的分泌也发生了有利的变化。
即使在 BMI 较低的、接受胰岛素治疗的 2 型糖尿病患者中，RYGB 也是治疗 MAFLD 的一种很有前途的方法，患者的组织学完全缓解。RYGB 恢复了氧化平衡、脂肪组织功能和胃肠道激素。
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