[Correlation analysis of clinical indicators and liver failure-related prognostic score associated with prognosis in patients with amanita phalloides poisoning].

OBJECTIVE: To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators. METHODS: A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning. RESULTS: A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×109/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95%CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95%CI was 0.74-0.99) and 66.0%, respectively. CONCLUSIONS: INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.

Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-ß1 signaling pathway.

Splenectomy has been reported to improve liver fibrosis in patients with cirrhosis and hypersplenism. However, the mechanisms remain unclear. Tumor necrosis factor superfamily 14 (TNFSF14; also known as LIGHT) is highly expressed in the context of fibrosis and promotes disease progression in patients with fibrotic diseases such as pulmonary and skin fibrosis. Here, we determined whether splenectomy controls the production of LIGHT to improve liver fibrosis. Splenectomy reduced serum LIGHT levels in cirrhotic patients with hypersplenism and a ConA-induced liver fibrosis mouse model. Blocking LIGHT resulted in the downregulation of TGF-ß1 in RAW264.7 cells. LIGHT treatment of RAW264.7 and JS1 cells in coculture regulated transforming growth factor-ß1 (TGF-ß1) expression through the activation of JNK signaling. Small interfering RNA-mediated silencing of lymphotoxin ß receptor (LTßR) in macrophages resulted in pronounced decreases in the levels of fibrosis and αSMA in JS1 cells. These results indicated that LIGHT bound to LTßR and drove liver fibrosis in vitro. Blocking TGF-ß1 abolished the effect of LIGHT in vitro. Furthermore, the administration of recombinant murine LIGHT protein-induced liver fibrosis with splenectomy, while blocking LIGHT without splenectomy improved liver fibrosis in vivo, revealing that the decrease in fibrosis following splenectomy was directly related to reduced levels of LIGHT. Thus, high levels of LIGHT derived from the spleen and hepatic macrophages activate JNK signaling and lead to increased TGF-ß1 production in hepatic macrophages. Splenectomy attenuates liver fibrosis by decreasing the expression of LIGHT.