Yang Yongqiang, Hartmann Phillipp, Schnabl Bernd
Department of Medicine, University of California San Diego CA, 92093 USA.
Department of Pediatrics, University of California San Diego CA, 92093 USA.
Microb Cell. 2024 Aug 26;11:328-338. doi: 10.15698/mic2024.08.836. eCollection 2024.
Alcohol-associated liver disease is highly prevalent worldwide, with alcohol-associated hepatitis as a severe form characterized by substantial morbidity, mortality, and economic burden. Gut bacterial dysbiosis has been linked to progression of alcohol-associated hepatitis. Fecal cytolysin secreted by the pathobiont () is associated with increased mortality in patients with alcohol-associated hepatitis. Although gelatinase is considered a virulence factor in , its prevalence and impact on alcohol-associated hepatitis patient outcomes remains unclear. In this study, 20 out of 65 (30.8%) patients with alcohol-associated hepatitis tested positive for gelatinase in their stool. There were no significant differences in 30-day and 90-day mortality between gelatinase-positive and gelatinase-negative patients (p=0.97 and p=0.48, respectively). Fecal gelatinase had a low discriminative ability for 30-day mortality (area under the curve [AUC] 0.50 vs fibrosis-4 Index (FIB-4) 0.75) and 90-day mortality compared with other established liver disease markers (AUC 0.57 vs FIB-4 0.79 or 'age, serum bilirubin, INR, and serum creatinine' (ABIC) score 0.78). Furthermore, fecal gelatinase was not an important feature for 30-day or 90-day mortality per random forest analysis. Finally, gelatinase-positive patients with alcohol-associated hepatitis did not exhibit more severe liver disease compared with gelatinase-negative patients. In conclusion, fecal gelatinase does not predict mortality or disease severity in patients with alcohol-associated hepatitis from our cohort.
酒精性肝病在全球范围内高度流行,酒精性肝炎是其严重形式,具有高发病率、高死亡率和经济负担。肠道细菌失调与酒精性肝炎的进展有关。致病共生菌()分泌的粪便溶细胞素与酒精性肝炎患者死亡率增加有关。尽管明胶酶被认为是致病共生菌中的一种毒力因子,但其在酒精性肝炎中的流行情况及其对患者预后的影响仍不清楚。在本研究中,65例酒精性肝炎患者中有20例(30.8%)粪便明胶酶检测呈阳性。明胶酶阳性和阴性患者在30天和90天死亡率方面无显著差异(分别为p = 0.97和p = 0.48)。与其他已确立的肝病标志物相比,粪便明胶酶对30天死亡率(曲线下面积[AUC]为0.50,而纤维化-4指数(FIB-4)为0.75)和90天死亡率的判别能力较低(AUC为0.57,而FIB-4为0.79或“年龄、血清胆红素、国际标准化比值和血清肌酐”(ABIC)评分为0.78)。此外,根据随机森林分析,粪便明胶酶不是30天或90天死亡率的重要特征。最后,与明胶酶阴性的酒精性肝炎患者相比,明胶酶阳性患者并未表现出更严重的肝病。总之,在我们的队列中,粪便明胶酶不能预测酒精性肝炎患者的死亡率或疾病严重程度。