Effect of transcutaneous auricular vagus nerve stimulation on postoperative liver injury in patients undergoing partial hepatectomy: a phase II clinical randomized trial

Perioperative liver injury is a common complication following partial hepatectomy in patients with hepatocellular carcinoma. Preclinical studies have shown that transcutaneous auricular vagus nerve stimulation (taVNS) has hepatoprotective effects, but clinical evidence remains limited. This study is a phase II, prospective, double-blind, randomized trial involving 140 patients undergoing partial hepatectomy, in which the active-taVNS group received 60-minute stimulation sessions at four time points: during the first hepatic pedicle clamping, after extubation in the post-anesthesia care unit, and on postoperative days 1 and 2 between 6:00 AM and 7:00 AM.

The primary outcome measure was serum alanine aminotransferase (ALT) levels on postoperative day 2. Results showed that the median ALT level in the active taVNS group was significantly lower than that in the sham stimulation group (144.5 U/L vs. 224.0 U/L; P = 0.002). The results suggest that taVNS may have an early and transient protective effect against hepatocellular injury, providing preliminary clinical evidence for its potential as a non-invasive intervention strategy for early liver damage following partial hepatectomy.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2400092005). The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. This study was supported in part by grants from the National Key R&D Program of China (2021ZD0203100 to J.L.C., 2022ZD0206200 to S.Z.); National Natural Science Foundation of China (NSFC81720108013, NSFC31771161, and NSFC81230025 to J.L.C.; NSFC82571437, NSFC82171227 and NSFC81300957 to H.L.; NSFC81771453 and NSFC31970937 to H.X.Z.; NSFC82371536 to S.Z.); Jiangsu Provincial Special Program of Medical Science (BL2014029 to J.L.C.); Basic and Clinical Research Center in Anesthesiology of Jiangsu Provincial “Science and Education for Health” Project (J.L.C.); Zhejiang Provincial Natural Science Foundation (LY22H090019 to H.L.); Jiangsu Provincial Natural Science Foundation (BK20190047 to H.X.Z.); the Priority Academic Program Development of Jiangsu Higher Education Institutions (19KJA610005 to H.X.Z.); Distinguished Professor Program of Jiangsu (H.X.Z.); Jiangsu Province Innovative and Entrepreneurial Talent Program and Jiangsu Province Innovative and Entrepreneurial Team Program (H.X.Z.); Xuzhou Medical University start-up grant for excellent scientist (D2018010 and D2019025D to H.X.Z.); the Natural Science Foundation of Shanghai (21ZR1411300 to Y.H.); and Shenkang Clinical Study Foundation of Shanghai (SHDC2020CR4061 to Y.H.).

These authors contributed equally: Yuanyuan Wang, Mingshu Tao, Zhengxiu Sun, Yongao Lin, Jinling Liu, Xingyu Xiong. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China Yuanyuan Wang, Mingshu Tao, Zhengxiu Sun, Yongao Lin, Jinling Liu, Xingyu Xiong, Pinghao Li, Tianxi Ma, Mingkai Zhou, Xiaoqin Guo, Chuyu Hang, Mingyuan Wang, Hongxing Zhang & Jun-Li Cao Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Shanghai, China Department of Anesthesiology, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, China Department of Anesthesiology, Huzhou Central Hospital, Huzhou, China The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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