Prognostic value of risk scoring systems for cirrhotic patients with variceal bleeding.

BACKGROUND: Acute variceal bleeding is one of the deadliest complications of cirrhosis, with a high risk of in-hospital rebleeding and mortality. Some risk scoring systems to predict clinical outcomes in patients with upper gastrointestinal bleeding have been developed. However, for cirrhotic patients with variceal bleeding, data regarding the predictive value of these prognostic scores in predicting in-hospital outcomes are limited and controversial. AIM: To validate and compare the overall performance of selected prognostic scoring systems for predicting in-hospital outcomes in cirrhotic patients with variceal bleeding. METHODS: From March 2017 to June 2019, cirrhotic patients with acute variceal bleeding were retrospectively enrolled at the Second Affiliated Hospital of Xi'an Jiaotong University. The clinical Rockall score (CRS), AIMS65 score (AIMS65), Glasgow-Blatchford score (GBS), modified GBS (mGBS), Canada-United Kingdom-Australia score (CANUKA), Child-Turcotte-Pugh score (CTP), model for end-stage liver disease (MELD) and MELD-Na were calculated. The overall performance of these prognostic scoring systems was evaluated. RESULTS: A total of 330 cirrhotic patients with variceal bleeding were enrolled; the rates of in-hospital rebleeding and mortality were 20.3% and 10.6%, respectively. For in-hospital rebleeding, the discriminative ability of the CTP and CRS were clinically acceptable, with area under the receiver operating characteristic curves (AUROCs) of 0.717 (0.648-0.787) and 0.716 (0.638-0.793), respectively. The other tested scoring systems had poor discriminative ability (AUROCs < 0.7). For in-hospital mortality, the CRS, CTP, AIMS65, MELD-Na and MELD showed excellent discriminative ability (AUROCs > 0.8). The AUROCs of the mGBS, CANUKA and GBS were relatively small, but clinically acceptable (AUROCs > 0.7). Furthermore, the calibration of all scoring systems was good for either in-hospital rebleeding or death. CONCLUSION: For cirrhotic patients with variceal bleeding, in-hospital rebleeding and mortality rates remain high. The CTP and CRS can be used clinically to predict in-hospital rebleeding. The performances of the CRS, CTP, AIMS65, MELD-Na and MELD are excellent at predicting in-hospital mortality.

[Changes in the intestinal microenvironment during development of alcoholic fatty liver disease and related effects of probiotic therapy].

OBJECTIVE: To investigate the initial changes in the gut microenvironment that accompany intestinal endotoxemia related to alcoholic fatty liver disease (ALD) in order to explore the potential initiating factors and to observe the effect of probiotic therapy on these factors. METHODS: Fifty Sprague-Dawley male rats were randomly divided into an ALD model group (alcoholic intragastric administration), an intervention group (ALD with probiotic intragastric administration), and a control group (physiological saline intragastric administration). Histological changes of the liver were evaluated using hematoxylin-eosin staining and light microscopy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides (TG), and plasma endotoxin and coli bacillus were determined. The structural integrity of intestinal mucosa and tight junctions were observed by transmission electron microscopy. Occludin protein expression in intestinal epithelial cells was detected by immunohistochemistry. RESULTS: After four weeks, the three groups showed significant differences in the plasma endotoxin levels [control: (0.67+/-0.14) pg/ml, model: (4.42+/-1.28) pg/ml, and intervention: (2.88+/-0.83) pg/ml; F = 27.288, P = 0.000] and numbers of Escherichia coli [control: (2.31+/-0.39) lg3/ml, model: (3.23+/-0.41) lg3/ml, and intervention: (2.24+/-0.44) lg3/ml; F = 10.692, P = 0.001]. The plasma endotoxin level and E. coli number were significantly higher in the model group than in the control group and the intervention group (all P less than 0.05). The three groups showed no significant differences in the levels of ALT, AST, and TG at four weeks. After eight weeks, however, all three serum markers were significantly different between the three groups [ALT: control: (62.33+/-7.12) U/L, model: (95.50+/-8.73) U/L, and intervention: (81.33+/-6.19) U/L; F = 18.051, P = 0.000]; [AST: control: (90.50+/-10.67) U/L, model: (130.00+/-14.91) U/L, and intervention: (110.33+/-7.26) U/L; F = 30.170, P = 0.000]; [TG: control: (0.84+/-0.84) mmol/L, model: (1.40+/-0.17) mmol/L, and intervention: (1.10+/-0.17) mmol/L; F = 10.592, P = 0.001]. In addition, the three groups showed significant differences in E. coli number [control: (2.23+/-0.46) lg3/ml, model: (4.81+/-0.29) lg3/ml, and intervention: (3.61+/-0.50) lg3/ml; F = 23.579, P = 0.000] and plasma endotoxin level [control: (0.52+/-0.21) pg/ml, model: (12.46+/-2.61) pg/ml, intervention: (6.83+/-1.74) pg/ml; F = 30.731, P = 0.000]. The levels of ALT, AST, TG and endotoxin, and the number of E. coli were all significantly higher in the model group than in the control group and the intervention group (all P less than 0.05). Small intestinal epithelial cell structural failure was more apparent and intercellular gaps more broad after eight weeks than after four weeks for all three groups. However, the intervention group showed clearer cell connection structures and less extensive cell gap broadening than the model group at eight weeks. After eight weeks, the occludin protein had become significantly down-regulated and distributed in a non-continuous pattern in the model group, as compared with the control group. However, the occludin protein expression was higher in intervention group than in the model group. CONCLUSION: Intestinal endotoxemia related to perturbations in the microenvironment occurs in the early phase of ALD, and the increased intestinal permeability appears to be the initial factor of elevated plasma endotoxin, which may lead to liver damage. Probiotic therapy can reduced plasma endotoxin levels and postpone ALD progression by altering the composition of the gut microbiota and up-regulating expression of the occludin protein in intestinal epithelial cells.