Tsutsui Yuriko, Yoshio Sachiyo, Tomiyama Takahiro, Shimagaki Tomonari, Itoh Shinji, Harada Noboru, Yoshida Yuichi, Yoshikawa Shiori, Kakazu Eiji, Kanto Tatsuya, Yoshizumi Tomoharu
Department of Liver Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hepatol Res. 2023 Jan;53(1):72-83. doi: 10.1111/hepr.13834. Epub 2022 Sep 12.
Although the survival rate after living-donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain-derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients.
We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes.
Patients who experienced sepsis showed worse short-term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child-Pugh C compared with Child-Pugh A or B. Serum BDNF was inversely correlated with Model for End-Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF.
Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status.
尽管活体肝移植（LDLT）后的生存率正在提高，但脓毒症仍然限制预后。免疫功能障碍和肌肉减少症在LDLT患者中经常出现，并增加感染易感性。脑源性神经营养因子（BDNF）是一种由免疫细胞和骨骼肌产生的肌动蛋白。我们旨在确定血清BDNF是否可能是LDLT患者脓毒症的一种可行生物标志物。
我们测量了124例接受LDLT的患者和9名健康志愿者的血清样本中的BDNF。我们检查了其与脓毒症发病率的相关性。为了阐明BDNF的来源，我们检查了其在淋巴细胞、骨骼肌细胞和肝细胞中的表达。
发生脓毒症的患者短期生存率较差。与健康志愿者相比，LDLT患者术前血清BDNF较低，与Child-Pugh A或B级相比，Child-Pugh C级患者的血清BDNF也较低。血清BDNF与终末期肝病模型和控制营养状况（CONUT）评分呈负相关，但与骨骼肌质量指数（SMI）呈弱正相关。多变量分析显示血清BDNF与脓毒症独立相关。术前血清BDNF比CONUT评分或SMI更能预测LDLT患者的脓毒症。血清BDNF与淋巴细胞计数呈正相关，尤其是T细胞。在体外，T细胞和骨骼肌细胞产生BDNF。
术前血清BDNF通过反映包括肝功能、营养状况和免疫状态在内的全身状况，可能是LDLT后脓毒症的预测生物标志物。
