Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Biotechmed-Graz, Graz, Austria.
Liver Int. 2023 Sep;43(9):1975-1983. doi: 10.1111/liv.15648. Epub 2023 Jun 19.
BACKGROUND & AIMS: On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.
Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.
Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3).
We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.
在全球范围内,肝硬化每年导致约 100 万人死亡。这种全身性疾病伴随着多种后遗症,包括微生物群改变、肠道通透性增加以及微生物成分易位进入全身循环。除了广泛研究细菌易位及其宿主-病原体相互作用的影响外,对于穿过肠道屏障的真菌成分的作用和影响知之甚少。
我们纳入了 70 例不同病因的肝硬化患者,通过 1,3-β-D-葡聚糖(BDG)检测,研究了真菌易位与肠道完整性、炎症和肝脏疾病严重程度/结局的生物标志物之间的关系。
与肝硬化 Child-Pugh 分级(CPC)-A 患者相比,肝硬化 CPC-B 患者更有可能出现阳性血清 BDG(优势比 5.4,95%可信区间 1.2-25.2)。BDG 与多种炎症标志物(sCD206、sCD163、白细胞介素 8、干扰素-γ诱导蛋白)呈中度正相关。BDG 阳性和阴性患者的死亡率有显著差异(对数秩检验,p=0.015)。多变量 Cox 回归模型得出的风险比为 6.8(95%可信区间 1.8-26.3)。
我们观察到随着肝硬化严重程度的增加,真菌易位的趋势增加,BDG 与炎症环境相关,BDG 对疾病结局有不良影响。为了更深入地了解(真菌)失调及其在肝硬化背景下的有害后果,需要在更大的队列中进行前瞻性连续检测,并结合真菌组分析来更详细地研究这些趋势。这将进一步阐明复杂的宿主-病原体相互作用,并可能为治疗干预提供切入点。