肝移植围手术期皮肤葡萄球菌属变化与终末期肝病患者瘙痒症状的相关性研究

Perioperative skin Staphylococcus dynamics and their association with pruritus in end-stage liver disease patients undergoing liver transplantation

摘要:

背景与目的 终末期肝病（ESLD）患者常伴有顽固性皮肤瘙痒，严重影响生活质量。尽管瘙痒缓解常被归因于肝移植后胆红素水平的恢复，但皮肤菌群在瘙痒发生中的作用尚未明确。本研究旨在探讨ESLD患者肝移植围手术期间皮肤微生态的动态变化及其与瘙痒症状的相关性。方法 纳入2022—2023年中南大学湘雅三医院器官移植中心15例ESLD患者，分别于肝移植术前、术后第7天及第30天采集小腿前区皮肤拭子；同时采集15名健康对照者同部位皮肤样本，采用16S rRNA测序分析菌群构成。同期评估瘙痒视觉模拟评分（VAS），并检测相关血清学指标，分析菌群变化与瘙痒程度及肝功能之间的相关性。结果 ESLD患者皮肤菌群β多样性显著异常，葡萄球菌属相对丰度显著升高（LDA>4），并与瘙痒VAS评分高度正相关（r=0.93，P_adj=3.08×10?1?）。术后第7天患者菌群α多样性下降、葡萄球菌属短暂激增，至第30天随瘙痒缓解逐步恢复至接近健康人水平。进一步分析显示，葡萄球菌属丰度与丙氨酸氨基转移酶、天门冬氨酸转移酶、总胆红素、直接胆红素、总胆汁酸、国际标准化比值呈正相关，与白蛋白呈负相关（均P_adj<0.05），且其丰度在中重度瘙痒患者（VAS评分>5）中显著升高。结论 ESLD患者在肝移植围手术期皮肤微生态明显紊乱，其中葡萄球菌属的异常增殖可能参与瘙痒的发生与加重。调控皮肤菌群，尤其是针对葡萄球菌属的干预，可能为改善ESLD患者瘙痒症状提供新策略。

Abstract:

Background and Aims Patients with end-stage liver disease (ESLD) frequently experience persistent pruritus, which significantly impairs their quality of life. Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels, the role of skin microbiota in developing pruritus remains unclear. This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points: before liver transplantation and on postoperative days 7 and 30. Skin samples from 15 age-matched healthy controls were collected at the same anatomical site. Microbial composition was analyzed using 16S rRNA sequencing. Meanwhile, pruritus severity was assessed using a visual analogue scale (VAS), and multiple serological indicators were measured to evaluate correlations between microbiota changes, pruritus severity, and liver function parameters.Results Compared with healthy controls, ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus (LDA>4), which was strongly correlated with VAS scores for pruritus (r=0.93, P_adj=3.08×10?1?). On postoperative day 7, α-diversity decreased, and Staphylococcus abundance peaked, then gradually normalized by day 30 as pruritus improved. Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, total bile acids, and international normalized ratio, and negatively correlated with albumin (all P_adj<0.05). Notably, Staphylococcus levels were significantly higher in patients with moderate to severe pruritus (VAS score>5).Conclusion ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation, characterized by an abnormal proliferation of Staphylococcus, which may contribute to the development and exacerbation of pruritus. Targeting the skin microbiome, particularly interventions against Staphylococcus, may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.