1.Adsorptive property of novel chitosan microspheres for plasma bilirubin and cytokines: A preliminary screening in vitro of novel biomaterials
Juan QU ; Tinghong LI ; Jing ZHANG ; Wei LU ; Zhengpu ZHANG
Chinese Journal of Tissue Engineering Research 2008;12(1):170-174
BACKGROUND: The effective therapy of artificial liver for severe hepatitis needs an absorbing material which possesses strong adsorptive property, high adsorption rate and good blood compatibility.OBJECTIVE: To study the adsorptive property of eight novel adsorbents for plasma bilirubin and cytokines in severe hepatitis patients. DESIGN: A controlled observation.SETTINGS: Graduate School of Tianjin Medical University, Tianjin Haihe Hospital, Tianjin Third Central Hospital and the Institute of Polymer Chemistry in Nankai University.PARTICIPANTS: All plasma was collected from 30 severe hepatitis patients hospitalized in Tianjin Third Central Hospital from November 2004 to November 2005. Informed consent was obtained from each patients. This experiment was approved by the hospital ethical committee. All the patients were divided into two groups at random: group 1 (n=10) and group 2 (n=20). The level of total bilirubin (TBiL) before therapy in two groups was (377.3±147.5) μmol/L and (327.6±140.1) μmol/L, respectively.METHODS: ①Adsorbents: Chitosan (Qingdao Lizhong Chitosan Factory, Shandong) with relative molecular weight 97 000 and de-acetyl grade 85%; Adsorbents No.1-3 were prepared by using 1%, 3%, 5% polyethyleneglycol (relative molecular weight 600) as porogenic agent. Adsorbent No.4 was aminated crosslinked chitosan microspheres; Adsorbent No.5 was divinyl-benzene crosslinked macroporous polystyrene microspheres; Adsorbent No.6 was post-crosslinked macroporous divinyl-benzene styrene copolymer microspheres; Adsorbents No.7 and 8 were chitosan wrapped adsorbent No.5 and 6.②Detection: Step 1: 3 mL plasma collected from each severe hepatitis patient in group 1 was absorbed with 1 mL of 8 kinds of adsorbents. Levels of plasma TBiL, direct bilirubin (DBiL) and indirect bilirubin (IBiL) before and after adsorption were determined by using the vanadate oxidation method to analyze the average adsorption capacity so as to screen the adsorbents with the better adsorptive properties. Step 2: 3 mL plasma collected from each severe hepatitis patient in group 2 was absorbed with 1 mL of two adsorbents selected from the step 1. The levels of bilirubin, interleukin-6 and tumor necrosis factor-α before and after the adsorption were analyzed by ELISA method.MAIN OUTCOME MEASURES: The levels of bilirubin and cytokines before and after the adsorption were determined.RESULTS: ①The data in the first step experiment showed that after No.4 and No.5 adsorbents were used, the level of plasma TBiL, DBiL and IBiL were significantly decreased (P < 0.01); no differences were found for other six kinds of adsorbents (P > 0.05).②The data in the second step experiment showed that the average levels of plasma TBiL, DBiL, IBiL, interleukin-6 and tumor necrosis factor-α were remarkably reduced after using adsorbents No.4 and No.5 (P < 0.01). Compared with adsorbent No.5, there were significant decrements for adsorbents No.4 (P < 0.01).CONCLUSION: Aminated chitosan microsphere has significant effects on adsorbing bilirubin and cytokines in plasma of severe hepatitis patients in vitro.
2.Noninvasive assessment of esophageal-gastric varices by spleen stiffness in liver cirrhosis patients
Tinghong LI ; Fang LIU ; Tao HAN ; Huiling XIANG ; Hongsheng ZHANG
Chinese Journal of Infectious Diseases 2012;30(10):603-608
Objective To investigate the value of spleen stiffness measured by transient elastography (FibroScan,FS) for diagnosing esophageal-gastric varices in liver cirrhosis patients.Methods A total of 259 cirrhotic patients in Tianjin Third Central Hospital from Apr 2011 to Apr 2012,and 30 healthy controls were enrolled.All the patients and controls were evaluated for spleen and liver stiffness by FS and 201 cirrhotic patients also underwent gastroscopy for the diagnosis of esophageal-gastric varices.By using gastroscopy as the gold standard,the receiver operating characteristic (ROC) curves of three parameters including spleen stiffness,liver stiffness and platelet/thickness of spleen were delineated for different disease stage.The areas under curves (AUC) were used to evaluate the value of these parameters in the diagnosis of esophageal-gastric varices.Results The spleen and liver stiffness values in cirrhotic patients were (44.64 ± 22.27) kPa and (24.27 ±18.89) kPa,respectively,while those in healthy controls were (20.94± 14.78) kPa and (6.12±5.77) kPa,respectively,which were both lower than cirrhotic patients (P<0.05).The stiffness values of liver and spleen both increased with higher Child-Pugh scores.And the liver stiffness values were different among groups (F=0.068,P =0.000),while the spleen stiffness values in patients with Child-Pugh A and B were different from that in patients with Child-Pugh C (P<0.05).In patients with moderate or serious esophageal-gastric varices,the spleen and liver stiffness values were significantly higher.The ROC curve analysis showed that the AUC of spleen stiffness,liver stiffness and platelet/thickness of spleen in the patients with moderate to serious esophageal-gastric varices were 0.918,0.749 and 0.743,respectively.The corresponding optimal cut-off values were 50.7 kPa,20.1 kPa and 1.65.The AUC,sensitivity and specificity of spleen stiffness were all higher than liver stiffness and platelet/thickness of spleen.Conclusion Spleen stiffness measured by transient elastography is a valuable parameter for non-invasive diagnosis of esophageal-gastric varices in cirrhotic patients.
3.Evaluation and influencing factors of the short-term prognosis of severe alcoholic hepatitis with different underlying liver diseases
Ping ZHU ; Heping ZHAO ; Tao HAN ; Qing YE ; Tinghong LI ; Huiling XIANG
Journal of Clinical Hepatology 2021;37(2):370-374
ObjectiveTo investigate the clinical features of patients with severe alcoholic hepatitis (AH) with different underlying liver diseases and the influencing factors for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 170 patients with severe AH who were admitted to Tianjin Third Central Hospital from August 2004 to August 2018, and according to the underlying liver disease, they were divided into group A (27 patients without liver cirrhosis), group B (52 patients with compensated liver cirrhosis), and group C (91 patients with decompensated liver cirrhosis). Related scores were calculated, including Maddrey’s discriminant function (MDF) score, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, Model for End-Stage Liver Disease (MELD) score, age-bilirubin-international normalized ratio-creatinine (ABIC) score, and Glasgow alcoholic hepatitis score (GAHS). An analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. Univariate and multivariate Cox regression analyses were used to screen out the independent influencing factors for the short-term prognosis of patients with severe AH. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate between groups. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUC) and 95% confidence interval (CI), sensitivity, and specificity for each predictive model, and the DeLong method was used for comparison. ResultsThe 28-day survival rates of patients in groups A, B, and C were 88.9%, 80.8%, and 51.6%, respectively, with a significant difference between the three groups (χ2=1983, P<0.001). The AUCs (95% CIs) of MELD score, MDF score, GAHS score, ABIC score, and CLIF-SOFA score were 0.584 (0.493-0.676), 0.696 (0.605-0.786), 0.644 (0.554-0.735), 0.745 (0.662-0.827), and 0.795 (0.726-0.863), respectively, in predicting 28-day mortality rate, and there were significant differences between CLIF-SOFA score and MDF, MELD, and GAHS scores (all P<0.05); CLIF-SOFA score had a sensitivity of 79.0% and a specificity of 67.9% at the optimal cut-off value of 850 points in predicting 28-day mortality rate. Different underlying liver diseases (hazard ratio [HR]=2.296, 95% CI: 1.356-3887, P=0.002) and hepatic encephalopathy (HR=1.911, 95% CI: 1.059-3.449, P=0.031) at disease onset were risk factors for 28-day prognosis. ConclusionPatients with severe AH with different underlying liver diseases have different clinical features and short-term prognoses. Different underlying liver diseases and hepatic encephalopathy at disease onset are closely associated with the 28-day prognosis of patients with severe AH. CLIF-SOFA score can predict the 28-day prognosis of patients with severe AH.
4.Influencing factors of rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding
Jia LIAN ; Tao HAN ; Huiling XIANG ; Yankai YANG ; Tinghong LI ; Lei LIU ; Baiguo XU ; Lixia SUN ; Fei WANG ; Yanchao FU
Journal of Clinical Hepatology 2021;37(9):2092-2096
Objective To investigate the influencing factors for rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding. Methods A retrospective analysis was performed for the clinical data of the patients with liver cirrhosis and esophagogastric variceal bleeding who were hospitalized in Tianjin Third Central Hospital from January 1, 2017 to December 31, 2018, and according to the presence or absence of rebleeding and bleeding time, the patients were divided into non-bleeding group ( n =148) and bleeding group ( n =119). The risk factors for rebleeding after gastroscopy were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Cox regression model was used for univariate and multivariate analyses. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of Child-Turcotte-Pugh (CTP), fibrosis-4 (FIB-4), and albumin-bilirubin (ALBI) scores in predicting rebleeding after gastroscopy, and MedCalc was used to compare the area under the ROC curve (AUC). Results A total of 267 patients with liver cirrhosis and esophagogastric variceal bleeding were enrolled, among whom 53 (19.9%) had liver cancer. A total of 119 patients suffered from rebleeding, with an overall rebleeding rate of 44.6% and a median time to rebleeding of 11.0 (0-39.0) months. The univariate Cox regression analysis showed that liver cancer (hazard ratio [ HR ]=0.377, P < 0.001), aspartate aminotransferase (AST) ( HR =1.002, P =0.025), serum Na ( HR =0.935, P =0.004), and FIB-4 ( HR =1.030, P =0.049) were associated with rebleeding, and the multivariate Cox regression analysis showed that liver cancer ( HR =0.357, P < 0.001), AST ( HR =1.003, P =0.030), prothrombin time (PT) ( HR =0.196, P =0.001), CTP score ( HR =1.289, P =0.014), FIB-4 ( HR =1.062, P =0.033), and ALBI score ( HR =0.433, P =0.011) were independent risk factors for rebleeding. CTP, FIB-4, and ALBI scores had an AUC of 0.711 (95% confidence interval [ CI ]: 0.647-0.776), 0.705 (95% CI : 0.640-0.770), and 0.730 (95% CI : 0.667-0.793), respectively, in predicting rebleeding. There was no significant difference in AUC between CTP, FIB-4, and ALBI scores ( P > 0.05). Conclusion Liver cancer, AST, PT, CTP score, FIB-4 score, and ALBI score are associated with rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding, among which CTP, FIB-4, and ALBI scores have a good value in predicting rebleeding outcome, while there is no significant difference in predictive ability between them.