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Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit ( t =2.413), platelet count ( t =6.584), total bilirubin (TBil) ( t =-8.070), prothrombin time (PT) ( U =77.500), international standardized ratio ( U =102.000), HBV DNA ( t =-2.767), IL-6 ( t =-16.543), and MELD score ( t =-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT ( r =0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[ OR ]=1.480, 95% confidence interval [ CI ]: 1.196~1.833, P =0.007) and MELD score ( OR =1.128, 95% CI : 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95% CI : 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95% CI : 0.687~0.989) or MELD score (AUC=0.783, 95% CI : 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF ( Z =-2.257, P =0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.
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ObjectiveTo investigate the protective effect of fecal microbiota transplantation (FMT) on mice with acute-on-chronic liver failure (ACLF) and its effect on intestinal flora. MethodsA total of 40 mice were randomly divided into control group (CON group), model group (MOD group), FMT group (feces of the mice in the CON group were used as fecal microbiota donor), and FMT model group (ANFMT group, with feces of the mice in the MOD group as fecal microbiota donor), with 10 mice in each group. All mice were observed in terms of body weight, death, liver histopathology, and changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and intestinal flora. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. ResultsCompared with the CON group, the MOD group had a significant reduction in body weight and significant increases in AST and ALT (all P＜0.05), as well as large patchy necrosis of hepatocytes, significant increases in Verrucomicrobia, Akkermansia, and Erysipelatoclostridium, and significant reductions in Dubosiella and Duncaniella (all P＜0.05). Compared with the CON group, the ANFMT group had a significant increase in AST (P＜0.05), hepatocyte swelling and mild ballooning degeneration, significant increases in Unclassified and Faecalibaculum, and significant reductions in Patescibacteria, Deferribacteres, Muribaculum, Candidatus_Saccharimonas, Rikenella, Odoribacter, Mucispirillum, and Lachnospiraceae_unclassified (all P＜0.05). Compared with the MOD group, the FMT group had significant reductions in AST and ALT (both P＜0.05), mild hepatocellular necrosis and marked ballooning degeneration, significant increases in Paramuribaculum and Bilophila, and significant reductions in Firmicutes, Rikenella, and Absiella (all P＜0.05). ConclusionIntestinal flora disturbance is observed in ACLF mice, and dysbacteriosis may lead to liver injury. FMT can alleviate liver inflammation in ACLF mice and thus exert a protective effect.
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ObjectiveTo investigate the value of Model for End-Stage Liver Disease (MELD) score combined with platelet-to-white blood cell ratio (PWR) in predicting the short-term prognosis of patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). MethodsA retrospective analysis was performed for the clinical data of 123 HBV-ACLF patients who were admitted to The First Affiliated Hospital of Suzhou University from June 2014 to June 2019, and according to the prognosis on day 90 after admission, these patients were divided into survival group with 53 patients and death group with 70 patients. Related clinical data were recorded, including age, sex, and total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), serum creatinine (SCr), Albumin (Alb), prealbumin (PAB), international normalized ratio (INR), white blood cell count (WBC), lymphocyte count (LY), monocyte count (MO), neutrophil count (NE), hemoglobin (Hb), and platelet count (PLT) within 24 hours after admission, and PWR and MELD score were calculated. The t-test and the Mann-Whitney U test were used for comparison of continuous data between two groups; univariate and multivariate binary logistic regression analyses were used to analyze the association between each factor and the prognosis of HBV-ACLF; a predictive model of MELD score combined with PWR was established. The receiver operating characteristic (ROC) curve was plotted, and Youden index, cut-off value, sensitivity, and specificity were calculated; the area under the ROC curve (AUC) was calculated for MELD score alone or combined with PWR to compare their value in predicting the prognosis of HBV-ACLF patients. ResultsThere were significant differences between the two groups in TBil, ALT, SCr, INR, WBC, MO, NE, Hb, PLT, PWR, and MELD score (all P＜0.05). TBil, SCr, INR, WBC, MO, NE, and MELD score were risk factors for prognosis of HBV-ACLF patients(all P＜0.05); PWR (odds ratio ［OR］=0.883, 95% confidence interval ［CI］: 0.798-0.977, P=0.016) and MELD score (OR=1.442, 95%CI: 1.225-1698, P＜0.001) were independent predictive factors for the prognosis of HBV-ACLF patients. MELD score combined with PWR had a stronger predictive efficiency than MELD score alone in predicting the prognosis of HBV-ACLF patients ［0.895 (95%CI: 0.827-0943) vs 0.842 (95%CI: 0.765-0.902), P＜0.05］. ConclusionMELD score combined with PWR can improve the efficiency of MELD score alone in predicting the prognosis of HBV-ACLF patients.
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ObjectiveTo investigate the value of interleukin-32 (IL-32) combined with Model for End-Stage Liver Disease (MELD) in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 92 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to the follow-up results at 3 months after diagnosis, the patients were divided into survival group with 40 patients and death group with 52 patients. ELISA was used to measure the serum level of IL-32. Clinical data of the patients were collected, including age, sex, underlying diseases, major complications, white blood cell count (WBC), platelet count (PLT), hematocrit (HCT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), serum creatinine (SCr), prothrombin time (PT), international normalized ratio (INR), and HBV DNA. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a Pearson correlation analysis was performed for IL-32 and other variables; a binary logistic regression analysis was performed to investigate the independent risk factors for the prognosis of patients with HBV-ACLF. The receiver operating characteristic(ROC) curve(AUC) was used to evaluate the value of IL-32 combined with MELD score in predicting the prognosis of patients with HBV-ACLF. The normal Z test was used for comparison of AUC. ResultsThere were significant differences between the two groups in HCT, PLT, TBil, SCr, PT, INR, HBV DNA, IL-32, and MELD score (all P＜0.05). IL-32 was positively correlated with TBil (r=0.952, P＜0.001) and MELD score (r=0850, P＜0.001). IL-32 (odds ratio ［OR］=1.137, 95% confidence interval ［CI］: 1040-1243, P=0.005) and MELD score (OR=1.055, 95% CI: 1.001-1.109, P=0.025) were independent risk factors for the death of HBV-ACLF patients. IL-32 combined with MELD score had the highest value in predicting the prognosis of patients with HBV-ACLF (AUC=0.992, 95% CI: 0.981-1000), with a significantly higher AUC than IL-32 (0.992 vs 0.984, Z=2.265, P＜0.05) and MELD score (0.992 vs 0877, Z=3182, P＜0.05). ConclusionBoth IL-32 and MELD score can predict the prognosis of patients with HBV-ACLF, and the combination of these two indicators has a better predictive value.
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ObjectiveTo investigate the role of coagulation function parameters and platelet indices in thrombotic events in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 56 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2019 were enrolled and divided into thrombotic complication (TC) group with 24 patients and non-thrombotic complication (NTC) group with 32 patients. A retrospective analysis was performed for their general clinical data on admission, and the patients were observed in terms of the changes in coagulation function, platelet count (PLT), and the platelet function-related index mean platelet volume (MPV) on days 1-7 after admission. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A repeated measures analysis of variance was used to compare coagulation markers within and between groups at different time points. ResultsOn admission, the TC group had a significantly younger age than the NTC group ［31.5 (29.0-34.0) years vs 48.5 (36.0-50.7) years, Z=-2.637, P=0.008］. On the day of admission, there was no significant difference in MPV between the TC group and the NTC group (P ＞0.05), while on days 2-7 after admission, there was a significant difference in MPV between the two groups (t=-2.696、-2.742、-2.894、-4.174、-3.945、-4.716,all P ＜0.01). In the TC group, MPV reached the peak value on day 5 of admission, with a mean value of 13.90±1.12 fl, which was higher than the range of normal values. On admission, all patients had a mean prothrombin time (PT) of 28.8±7.2 s, a mean activated partial thromboplastin time (APTT) of 50.5±8.7 s, and a mean international normalized ratio (INR) of 2.6±0.7, which were higher than normal values; all patients had a mean fibrinogen (Fb) level of 1.16±0.3 g/L and a mean PLT of (107.7±26.5)×109/L, which were lower than normal values. There were no significant differences in PT, APTT, Fb, INR, and PLT between the TC group and the NTC group (all P ＞0.05). ConclusionCoagulation disorder in patients with liver failure is more of a low-equilibrium state, which is complex and heterogeneous and requires individualized treatment. For patients with HBV-ACLF, the development of thrombotic events may be more associated with platelet function than PLT or conventional coagulation markers.
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ObjectiveTo investigate the association between mean platelet volume (MPV) and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) and the value of MPV in prognostic evaluation. MethodsA retrospective analysis was performed for the clinical data of 37 patients with hepatitis B cirrhosis, 44 patients with HBV-ACLF, and 27 patients with chronic hepatitis B, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, from January 2015 to December 2019, as well as 24 individuals who underwent physical examination during the same period of time. Related clinical data included sex, age, total bilirubin (TBil), creatinine (Cr), blood urea nitrogen (BUN), albumin (Alb), blood ammonia (NH3), routine blood test results, Model for End-Stage Liver Disease (MELD) score, and blood coagulation parameters. According to prognosis, the patients with HBV-ACLF patients were divided into improvement group with 19 patients and non-improvement group with 25 patients, and the patients were followed up for 3 months. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank sum test was used for comparison within each group， the Mann-Whitney U test was used for comparison between two groups； a binary logistic regression analysis was used to investigate the independent influencing factors for prognosis, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. ResultsThere were significant differences in MPV, platelet count, prothrombin time (PT), international normalized ratio (INR), Alb, BUN, TBil, and MELD score between the liver cirrhosis group, the HBV-ACLF group, the chronic hepatitis group, and the healthy group (χ2=39.031， 75.837, 59.894, 56.033, 22.760, 83.353 and 70.299, all P＜0.001). Further comparison of MPV between two groups showed that the HBV-ACLF group had a significantly higher MPV than the healthy group and the chronic hepatitis group (Z=9.076 and 4.435, both corrected P＜0.001), and the liver cirrhosis group had a significantly higher MPV than the healthy group (Z=2.646, corrected P=0.049). For the patients with HBV-ACLF, there were significant differences in MPV, age, PT, INR, and MELD score between the improvement group and the non-improvement group (Z=-3.710， -2.726， -2.678， -2.322 and -2.610, all P＜0.05), and further binary logistic regression analysis showed that MPV (odds ratio ［OR］=1.175, 95% confidence interval ［CI］: 1.067-2.756, P=0.026) and MELD score (OR=1.643, 95% CI: 1.021-2.644, P=0.041) were independent influencing factors for the prognosis of HBV-ACLF. MPV alone, MELD score alone, and MPV combined with MELD score had an area under the ROC curve of 0.742, 0.731, and 0.791, respectively, in predicting the prognosis of HBV-ACLF, and MPV combined with MELD score had relatively high sensitivity (0.72) and specificity (0.895). ConclusionMPV is an independent influencing factor for the prognosis of HBV-ACLF and has a good value in predicting prognosis. MPV combined with MELD score has advantages over MPV or MELD score alone in predicting the prognosis of HBV-ACLF.
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ObjectiveTo investigate the level of vascular endothelial growth factor (VEGF) in the peripheral blood of patients with liver cirrhosis and portal vein thrombosis (PVT) and its clinical significance in the diagnosis of liver cirrhosis with PVT. MethodsA total of 60 patients with liver cirrhosis and PVT who were followed up or hospitalized in the outpatient service of The First Affiliated Hospital of Soochow University from January 2017 to December 2019 were enrolled as PVT group, and 161 patients with liver cirrhosis and portal hypertension who had no thrombi were enrolled as LC group. Related clinical data were collected, including sex, age, white blood cell count, platelet count, total bilirubin, alanine aminotransferase, albumin, prothrombin time, international normalized ratio, and antithrombin Ⅲ. Double-antibody sandwich ELISA was used to measure the serum level of VEGF. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Pearson correlation test was used for correlation analysis, and a binary logistic regression analysis was used to investigate the risk factors for PVT in patients with liver cirrhosis. ResultsThe comparison of baseline indices showed that there was a significant difference in serum VEGF between the PVT group and the LC group (P＜0.05). The comparison of the patients with Child-Pugh class A, B or C disease showed that there was a significant difference in serum VEGF between the two groups (Z=3.749， 5.469， all P＜0.05). The stepwise logistic regression analysis showed that only serum VEGF (odds ratio=1004, 95% confidence interval: 1.003-1.006, P＜0.001) was an independent risk factor for liver cirrhosis with PVT. ConclusionPatients with liver cirrhosis and PVT tend to have a high level of VEGF in peripheral blood, which provides guidance for clinical diagnosis.
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Objective To analyze the subjective and objective misdiagnostic reasons of brucellosis in Suzhou City. Methods The clinical data of inpatients with brucellosis from the department of infectious diseases, the First Affiliated Hospital of Soochow University from 2016 to 2018 were collected. The main onset methods, the first consultation department, the diagnosis and treatment process, and the main diagnosis were analyzed. Simultaneously, a questionnaire survey was conducted among doctors from different departments in Suzhou City. To investigate the knowledge and diagnosis of brucellosis by electronic questionnaire, and analyze the results. Results Totally 24 brucellosis cases were collected. Fever (13 cases, 54.17％), lumbago/arthralgia (6 cases, 25.00％) or both (3 cases, 12.50％) were the main initial symptoms, while a patient with fever, arthralgia and orchitis (1 case, 4.17％) and another with purpura (1 case, 4.17％ ) were also admitted. The 24 patients were distributed among 10 different departments, in which the department of infectious diseases (6 cases, 25.00％) and orthopedics (5 cases, 20.83％) dominated. Brucellosis was considered in only 2 patients (8.33％) before pathogen results, and the main suspected diagnosis were malignant hematopathy/lymphoma (7 cases, 29.17％), sepsis (5 cases, 20.83％), and tuberculosis (4 cases, 16.67％). Totally 124 questionnaires were collected and analyzed. We divided them into 2 groups: department of infectious diseases (52 / 124, 41.94％) and other departments (72/124, 58.06％). The proportion of answer "yes" for the question Suzhou is the epidemic area of brucellosis, question whether brucellosis is considered in suspected patients, question whether the epidemiology is collected and question how and where to conduct the serological test was 38.71％ (48/124), 32.26％ (40/124), 53.23％ (66/124) and 29.84％ (37/124), respectively. The positive answer in the department of infectious diseases (24/52, 46.15％) was significantly higher than those of others (16/72, 22.22％,χ2 = 7.913, P < 0.05). The respondents thought the serological test could not be conducted, because of that the non-pasture doctors were not familiar with the test procedure, which was complex (93/124, 75.00％) and the disease was not considered (85/124, 68.55％). And the respondents thought measures helpful to reduce misdiagnosis should include setting up serological test or simplifying the procedure (96/124, 77.42％), massed learning organized by related administrations (95/124, 76.61％) and learning by books, papers and classes (72/124, 58.06％). Conclusion There is obvious clinical misdiagnosis of brucellosis in Suzhou City, which may be caused by Suzhou doctors not paying enough attention to brucellosis, being unfamiliar with the inspection process and complicated inspection process.
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Objective@#To explore the prognostic value of model for end-stage liver disease (MELD) combined with arterial blood lactate (Lac) in admitted patients with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF).@*Methods@#Clinical data of 97 cases with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF) admitted to the First Affiliated Hospital of Suzhou University between March 2016 and March 2018 was retrospectively analyzed. Age, gender, complications, MELD score, lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), serum albumin (Alb), high-sensitivity C-reactive protein (CRP), white blood cell count (WBC), platelet count (PLT), hematocrit (Hct), quantification of HBV DNA and HBsAg, and organ support treatment (artificial liver support system, renal replacement therapy and mechanical ventilation ) were documented after admission. The primary endpoint of treatment was death due to ineffective medical treatment during hospitalization, abandonment of medical treatment due to deterioration of the health condition, and switch to liver transplantation for patients with poor medical treatment. The risk factors for primary endpoint of treatment were analyzed by binary logistic regression. Hosmer-Lemeshow test was used to evaluate the goodness of fit for the scoring system, and the ROC to predict the prognosis of MELD-Lac.@*Results@#Ninety-seven cases with HBV-ACLF were included, 56 cases had good prognosis, and 41 cases had bad prognosis (including two cases with poor medical treatment and liver transplantation). The overall improvement rate was 57.7%. MELD score and Lac value in treated group was significantly lower than non-treated group. Bivariable and multivariable logistic regression analysis showed that the MELD score [odds ratio (OR = 1.806)], and Lac score [odds ratio (OR = 1.820)] was the risk factor for hospitalization and mortality in patients with liver failure (P < 0.05). The area under the ROC curve (AUC) and the 95% confidence interval (95% CI) of prognostic patients with MELD-Lac were significantly better than Lac and MELD scores [0.923 (0.84 to 1.00) vs. 0.804 (0.067 to 0.942) and 0.864 (0.75). 0.977)], P < 0.05. When the MELD-Lac Youden index was set at 0.746, the optimal threshold was 18.36, and the sensitivity and specificity were 91.3% and 83.3%, respectively.@*Conclusion@#MELD-Lac score has a high prognostic value in HBV-ACLF patients.
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Objective@#To analyze the subjective and objective misdiagnostic reasons of brucellosis in Suzhou City.@*Methods@#The clinical data of inpatients with brucellosis from the department of infectious diseases, the First Affiliated Hospital of Soochow University from 2016 to 2018 were collected. The main onset methods, the first consultation department, the diagnosis and treatment process, and the main diagnosis were analyzed. Simultaneously, a questionnaire survey was conducted among doctors from different departments in Suzhou City. To investigate the knowledge and diagnosis of brucellosis by electronic questionnaire, and analyze the results.@*Results@#Totally 24 brucellosis cases were collected. Fever (13 cases, 54.17%), lumbago/arthralgia (6 cases, 25.00%) or both (3 cases, 12.50%) were the main initial symptoms, while a patient with fever, arthralgia and orchitis(1 case, 4.17%) and another with purpura (1 case, 4.17%) were also admitted. The 24 patients were distributed among 10 different departments, in which the department of infectious diseases (6 cases, 25.00%) and orthopedics (5 cases, 20.83%) dominated. Brucellosis was considered in only 2 patients (8.33%) before pathogen results, and the main suspected diagnosis were malignant hematopathy/lymphoma (7 cases, 29.17%), sepsis (5 cases, 20.83%), and tuberculosis (4 cases, 16.67%). Totally 124 questionnaires were collected and analyzed. We divided them into 2 groups: department of infectious diseases (52/124, 41.94%) and other departments (72/124, 58.06%). The proportion of answer "yes" for the question Suzhou is the epidemic area of brucellosis, question whether brucellosis is considered in suspected patients, question whether the epidemiology is collected and question how and where to conduct the serological test was 38.71% (48/124), 32.26% (40/124), 53.23% (66/124) and 29.84% (37/124), respectively. The positive answer in the department of infectious diseases (24/52, 46.15%) was significantly higher than those of others (16/72, 22.22%, χ2=7.913, P < 0.05). The respondents thought the serological test could not be conducted, because of that the non-pasture doctors were not familiar with the test procedure, which was complex (93/124, 75.00%) and the disease was not considered (85/124, 68.55%). And the respondents thought measures helpful to reduce misdiagnosis should include setting up serological test or simplifying the procedure (96/124, 77.42%), massed learning organized by related administrations (95/124, 76.61%) and learning by books, papers and classes (72/124, 58.06%).@*Conclusion@#There is obvious clinical misdiagnosis of brucellosis in Suzhou City, which may be caused by Suzhou doctors not paying enough attention to brucellosis, being unfamiliar with the inspection process and complicated inspection process.
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Objective To evaluate therapeutic effects of bone marrow mesenchymal stem cells(MSC)derived exosomes on alcohol-induced liver injury.Methods Eighteen male C57BL/6 mice aged 6 to 8 week were randomly divided into control group,model group and exosomes group,with 6 mice in each group.The mice in the model group and the exosomes group were fed with Lieber-DeCarli ad libitum diet(Dyets Inc.)for 4 weeks,followed by gavage a bolus of ethanol at day 26,27 and 28.The mice in the control group matched the alcohol-derived calories with dextran-maltose.Meanwhile,the mice in exosomes group were injected with MSC-exosomes via the tail vein at day 14 and 26.After the experiment,serum levels of alanine aminotransferase(ALT)and aspartate aminotransaminase(AST)were detected,and the pathological changes of liver tissues were observed.The expressions of nuclear factor erythroid 2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),CD63,CD81,TSG101 and Cytochrome C were analyzed by Western blot,and mRNA levels of Nrf-2,HO-1,interleukin(IL)-10 and IL-17 were analyzed by real-time polymerase chain reaction(RT-PCR).The commercial kits were used to detect serum IL-10,IL-17 levels and liver tissue malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)oxidative stress indicators.The numbers of regulatory T cell(Treg)and help T(Th)17 cells in the liver were analyzed by flow cytometry.One-way analysis of variance was used for comparison between groups.Results MSC-exosomes expressed positive markers CD63,CD81 and TSG101,but did not express the negative markers Cytochrome C.The serum ALT and AST levels in model group were(87.3±25.1)U/L and(223.2±43.5)U/L,respectively,while those in exosomes group were(47.7±12.0)U/L and(128.2±33.6)U/L,respectively.The differences between the two groups were both statistically significant(F=12.818 and 12.226,respectively,both P<0.05).Compared with control group,the SOD activity and GSH level in the model group significantly decreased with statistically significant differences(F=4.245 and 24.074,respectively,both P <0.05).Lieber-DeCarli ethanol feeding significantly increased intrahepatic MDA level in the model mice,which was reversed by MSC-exosomes supplementation,and the difference was statistically significant(F=36.675,P <0.05).Compared with control group,the intrahepatic protein expressions of Nrf-2 and HO-1 in model group were significantly decreased,while the expressions in exosomes group were obviously increased.The differences were statistically significant(F=33.623 and 14.960,respectively,both P <0.05).The expression trends of Nrf-2 and HO-1 mRNA were the same as those of protein expressions(F=20.784 and 276.336,respectively,both P <0.05).The proportions of liver Treg/Th17 in the control group,model group and exosomes group were 4.3±0.9,0.4±0.2,and 3.4±0.5,respectively.The differences among groups were statistically significant(F=64.227,P <0.05).Compared with control group,the serum protein and intrahepatic gene expression of IL-17 in the model group were significantly increased,which were reversed by MSC-exosomes treatment.The differences were statistically significant(F=15.581 and 40.095,respectively,both P<0.05).Serum IL-10 protein levels and intrahepatic IL-10 gene expression were significantly decreased after Lieber-DeCarli ethanol feeding,which were lower than the exosomes group.The differences were statistically significant(F=98.268 and 153.743,respectively,both P <0.05).Conclusions MSC-exosomes transplantation may relieve alcohol-induced liver injury.The mechanism could involve reduction of oxidative stress in the liver via regulating Nrf-2/HO-1 and normalizing the balance of Treg and Th17 cells.
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Objective To explore the predictive value of neutrophil-to-lymphocyte ratio on the prognosis of H7N9 avian influenza.Methods A retrospective analysis was conducted on 28 H7N9 avian influenza patients (treatment group) at the First Affiliated Hospital of Soochow University from April 2013 to January 2016.Thirty healthy physical examiners in the same period were enrolled as the healthy control group.The 28 patients were followed up for half a year and divided into the improvement group (18 cases) and the death group (10 cases) according to the clinical prognosis.Inflammatory indicators including white blood cells (WBC),neutrophil (N),lymphocyte (L),monocytes (M),platelet (PLT),creatine kinase (CK),lactate dehydrogenase (LDH),high sensitive C reactive protein were collected at day 1,day 3 and week 1 of admission.Calculation of neutrophil-to-lymphocyte ratio (NLR),platelet-to-lymphocyte ratio (PLR),lymphocyte-to-monocyte ratio (LMR),△NLR3 (day 3 of admission NLR-on day 1 of admission NLR),△NLR7 (week 1 of admission NLR-day 3 of admission NLR) and so on calculating △PLR3,△PLR7,△LMR3,△LMR7.Differences of the above indicators between the improvement group and death group were compared.The measurement data with normal distribution were tested by t-test of two independent samples,and the count data with non-normal distribution were tested by Mann-Whitney U-test.Univariate and multivariate logistic regression analysis to explore the prognostic factors and the working characteristic curve of subjects was used to evaluate the predictive value of inflammatory response indexes for H7N9 avian influenza death.Results In the treatment group,the baseline WBC,L,N,PLT,the proportion of lymphocytes,neutrophils,monocytes,and NLR,PLR,and LMR were all statistically different compared with the healthy control group (all P ＜0.01).After treatment,day 3 NLR,△NLR3 in improvement group were both significantly decreased to 10.93 (15.71)and0.87 (-15.63),respectively when compared with death group (17.62[23.63] and 7.42[22.68],respectively) (Z =-2.16 and-2.014,respectively,both P＜0.05).Day 7 NLR,△NLR7 in improved group were 6.51 (13.23) and-0.37 (-12.38),respectively,which were both lower than those of death group (27.90 [25.64] and 11.54 [-26.22]) with statistically significant differences (Z =-2.444 and -2.111,respectively,both P ＜ 0.05).Multivariate logistic regression analysis indicates that △NLR3 is the main factor that affects the prognosis of the H7N9 infection (odds ratio [OR] =1.153,95％ confidence interval [CI]:1.052-1.263,P =0.002).Reciver operating characteristic curve analysis showed that the area under the curve was 0.733 (95 ％ CI:0.532-0.935,P =0.044).Based on the principle of Youden index,the cutoff value of △NLR3 to predict the death risk of H7N9 avian influenza was 5.453 with sensitivity of 0.700 and the specificity of 0.722.The mortality was higher when △NLR3 was higher than 5.453.Conclusions Dynamic monitoring NLR,especially △NLR3 may reflect the condition and prognosis of H7N9 infection,which is an independent predictor of death.
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Objective@#To explore the characteristics underlying Th1/Th2/Th17 expression level after entecavir (ETV) discontinuation of chronic hepatitis B (CHB) patients who were HBeAg-positive and define the role of Th1/Th2/Th17 in maintaining virological response after ETV discontinuation.@*Methods@#We selected 112 HBeAg positive CHB patients who met the withdrawal criteria according to the guideline of prevention and treatment of chronic hepatitis B (2010 version), and we also separated them into virology sustained response (SVR) group and virological relapse (VR) group according to the recurrence in 52 weeks. We detected serum level of Th1/Th2/h17 related cytokines during 0, 12, 24 and 52 weeks follow-up to further analyze their dynamic changes and expression differences.@*Results@#The results of the study reveals that serum levels of IFN-γ in the group of SVR were at a higher level compared with VR group during follow-up (all P<0.05). While, the serum level of IL-10 decreased in SVR group and was lower than the paired IL-10 level in VR group with significance during follow-up. In VR group, the serum level of IFN-γ decreased during the first 24 weeks after ETV withdrawal, and after then, the level rose. The serum levels of IFN-γ (Th1) in SVR patients were significantly higher than those in VR patients in the different follow-up time points after ETV discontinuation (all P<0.05). And the serum levels of IL-10 (Th2) in SVR patients were significantly lower than that in VR patients (all P<0.05). The comparison of serum levels of IL-17A (Th17) between the two groups had no significant difference (all P>0.005).@*Conclusions@#The serum level of IFN-γ in SVR group maintained a high level is conducive to maintaining virological response after ETV withdrawal and high level of IL-10 may be related to virologic relapse.
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Liver failure refers to a series of clinical syndromes manifesting as coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other decompensated abnormalities due to serious hepatic dysfunction or decompensation in terms of synthesis, detoxification, excretion, and biological transformation caused by a variety of factors. In recent years, with the development of the research on immunological pathogenesis of liver failure, the "three-hit" theory clarifies the pathogenesis of liver failure. Major therapeutic strategies for liver failure are to prevent hepatocyte necrosis, promote hepatocyte regeneration, create a good internal environment for hepatocyte regeneration, and actively prevent and treat complications. An understanding of the immune status of liver failure patients and early application of glucocorticoids at right timing may help to improve prognosis and reduce adverse reactions. Establishment of a quantitative or functional balance between different cell subsets and new thoughts on some key cytokines may provide new directions and targets for immune regulation of liver failure.
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Objective To investigate the changes and clinical significance of peripheral blood T lymphocyte subsets and cytokines in influenza A (H7N9) virus infection patients.Methods Twenty-three patients with H7N9 virus infection who received treatment at the First Affiliated Hospital of Soochow University from April 2013 to April 2015 were enrolled as case group.Twenty healthy subjects in the outpatient clinic during the same period were selected as control group.The percentages of T lymphocyte subsets in the peripheral blood including CD3+CD4+ T cells, CD3+CD8+ T cells, regulatory T lymphocytes (Treg), Th17, CD3+CD8-interferon (IFN)-γ+ (Th1) cells and CD3+CD8-IL-4+ (Th2) cells were detected by flow cytometry.The changes of plasma cytokines including interleukin (IL)-8, IL-18, interferon-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1b were quantified by Bio-Plex Pro human cytokine Group Ⅰ 27-plex panel and Group Ⅱ 21-plex panel.The normality test was performed by Kolmogorov-Smirnov test.Two independent samples t test were used to compare the two groups.Results The percentages of CD3+CD4+ and CD3+CD8+ T cells before treatment in case group were significantly lower than control group ([27.90±10.19]% vs [38.75±6.78]%, t=-2.726, P=0.012;[14.82±7.72]% vs [22.79±6.12]%, t=-2.556, P=0.018), while the percentages of Th17 and Th2 before treatment in case group were significantly higher than control group ([2.64±1.40]% vs [0.29±0.21]%, t=4.668, P0.05).Before treatment, levels of IL-8, IL-18, IP-10 and MIP-1b of case group were significantly higher than those in control group (IL-8: [23.19±14.35] vs [12.78±6.76] ng/L, t=2.277, P=0.035;IL-18:[230.55±230.18] vs [72.80±27.91] ng/L, t=2.348, P=0.036;IP-10:[28 870.55±41 815.22] vs [1 356.13±1 093.10] ng/L, t=2.371, P=0.035;MIP-1b: [197.74±119.87] vs [118.51±41.86] ng/L, t=2.198, P=0.043).Conclusions Patients with H7N9 virus infection exhibit an imbalance of T lymphocyte subsets.It is very important to monitor the changes of T lymphocyte subsets in those patients for clinical prognosis.A storm of cytokines could exist during H7N9 virus infection, which may be the main reason for multiple organ failure.
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Objective To study the correlation between interleukin(IL)-21 and the recurrence of chronic hepatitis B(CHB)in hepatitis B e antigen(HBeAg)-positive patients after discontinuation of entecavir(ETV).Methods A total of 112 HBeAg-positive CHB patients treated with ETV were enrolled.Serum levels of IL-21 at week 0,12,24 and 52 after ETV discontinuation were detected.The Cox regression model was used to analyze the correlation between IL-21 and the recurrence after ETV discontinuation.The receiver operating characteristic(ROC)curve was applied to determine the predictive value of IL-21 for CHB recurrence after ETV discontinuation.The expression differences of IL-21 were compared between sustained viral response(SVR)group and viral relapse(VR)group.The t test and Chi-square test were used for statistical analysis.Results The serum levels of IL-21 in SVR group at week 0,12,24 and 52 after ETV withdrawal were(60.0 ± 10.8),(60.2 ± 14.7),(60.6 ± 19.5)and (61.2 ± 15.4)ng/L,respectively,which were all significantly higher than those in VR group(47.5 ± 10.7),(47.3 ± 12.9),(46.9 ± 12.2)and(46.4 ± 12.8)ng/L,respectively(t=6.153,4.926,4.382 and 5.515,respectively,all P< 0.01).The area under curve(AUC)was 0.811(95% CI:0.728 ~0.893,P<0.01)and the best cut-off value of serum IL-21 level was 49.8 ng/L.The recurrence rates of patients with serum IL-21 level ≥49.8 ng/L and <49.8 ng/L at time of ETV withdrawal was 25.4%(16/63)and 77.6%(38/49),respectively.The difference was statistically significant(χ2=30.027,P<0.01).The serum IL-21 level at the time of drug withdrawal(P= 0.005),serum hepatitis B surface antigen(HBsAg)level at the time of HBeAg seroconversion(P= 0.008)and age(P= 0.016)were factors associated with CHB recurrence after ETV withdrawal by multivariate Cox model analysis.The serum levels of ALT,HBV DNA,HBeAg and HBsAg in SVR group were significantly lower than those of VR group at week 12,24 and 52 after ETV withdrawal(t= -5.968,-7.691,-8.093; -3.047,-9.477,-28.900;-2.872,-10.424,-18.330;-4.633,-4.030 and -5.032,respectively;all P<0.01).Serum level of IL-21 was negatively correlated with HBsAg in SVR group after ETV withdrawal (r= -0.241,P<0.01),while positively correlated with HBsAg in VR group(r=0.286,P<0.01). Conclusions The serum IL-21 level at the time of drug withdrawal is associated with the recurrence after ETV discontinuation.IL-2l may play an important role as an immunomodulatory factor in maintaining virological responses in HBeAg-positive CHB patients after ETV withdrawal.
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Objective To investigate the serum γ-glutamyl transferase(γ-GT)level and its clinical significances in hepatitis B virus(HBV)-liver failure(LF)patients.Methods γ-GT levels were detected in 89 LF patients,30 cases with cirrhosis and 30 healthy controls.Difference of serum γ-GT between survival group and death group in LF patients and dynamics of γ-GT after hospitalization were studied. Survival rate between γ-GT increase group and decrease group were compared.The associations of γ-GT with model for end stage live disease(MELD)and prealbumin were calculated.Results At baseline,the γ-GT levels in LF,cirrhosis and healthy control groups were(149.61 ± 69.86),(123.96 ± 59.52)and (48.28 ± 10.25)U/L,respectively,the difference among groups was significant(F= 178.150,P<0.05).The survival group in LF patients showed significant increase of γ-GT one week after hospitalization compared with death group([75.27 ± 10.34]vs[29.47 ± 5.05],t=5.40,P<0.05). The γ-GT increase group showed higher survival rate than γ-GT decrease group[76.19%(48/63)vs 23.08%[6/26],χ2=21.76,P<0.05].Serum γ-GT level in LF patients was positively correlated with both MELD score and prealbumin(r=0.709 and -0.627,respectively,both P<0.05).Conclusions The rise of γ-GT may indicate a better prognosis in LF patients.Serum γ-GT positively correlates with prealbumin and both could reflect the regeneration of hepatocytes.
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Objective To observe the expression level of macrophage stimulating protein (MSP) in acute on-chronic liver.failure (ACLF) patients,and to explore the clinical significance and correlation with different immune regulatory factors.Methods The double antigen sandwich enzyme-linked immunosorbent assay method was used to detect MSP in the peripheral blood of 45 patients who were diagnosed with ACLF and 32 cases of chronic hepatitis B (CHB).The MSP levels were compared among ACLF patients with different outcomes,and the MSP level of healthy person was used as control.Meanwhile,liver function and hepatitis B virus (HBV) load were detected,and the expressions of peripheral blood CD4+ interferon (IFN)γ+ (helper T cell 1 Th1),CD4+ interleukin (IL)-4+ (helper T cell 2,Th2),CD4+IL-17+ (helper T cell 17,Th17) and CD4+ CD25+ Foxp3+ (regular T cell,Treg) were measured by flow cytometry.The comparison of means between two samples was done by t test,and oneway ANOVA and linear correlation analysis were also used.Results The serum MSP levels in ACLF patients,CHB group and healthy control were (1.65±0.46) ng/mL,(1.43±0.32) ng/mL and (1.23±0.21) ng/mL,respectively.The serum MSP level in ACLF patients was significantly higher than both CHB patients (t=2.163,P=0.035) and healthy control (t=4.032,P=0.01).The MSP level in ACLF survival group was statistically higher compared with ACLF death group ([2.29 ± 0.42] ng/mL vs [1.42±0.17] ng/mL,t=1.973,P=0.042).Th2,Th17 cells in ACLF group,CHB group and healthy control group were (1.51±0.27) ％ and (1.94±1.02)％,(0.42±0.08)％ and (0.55±0.36)％,(0.23±0.19) ％ and (0.26±0.19) ％,respectively,which were all significantly different (F=7.759 and 37.229,respectively;both P＜0.01).The MSP level was positively associated with the number of Th2 (r=0.386,P=0.032) and Th17 (r=0.644,P=0.000),and the ratio of Th17/Treg (r =0.605,P=0.000);while it was negatively associated with the number of Th1 (r=-0.212),Treg (r=-0.262) and the ratio of Th1/Th2 (r=-0.394) (all P＞0.05).Conclusion MSP is involved in the progress of ACLF,and it may be associated with clinical outcomes and cellular immune imbalance of ACLF patients.
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Oral anti-viral agents nucleos (t)ide analogues (NAs) are widely used in treatment of chronic hepatitis B (CHB) since they are well-tolerated in most patients.But clinical relapse occurs in a considerable part of patients after the cessation of NAs therapy.This paper reviews factors related to clinical relapse, including time for drug withdrawal, cccDNA level, age, baseline alanine aminotransferase (ALT) and HBV DNA levels, type of NAs, serum level of HBsAg and the immune status of patients.
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MicroRNAs (miRNAs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes and play important roles in proliferation,differentiation,development and metabolism of cells.This paper reviews the research progress on miRNAs involvement in liver diseases,including viral hepatitis,fatty liver,drug induced liver disease,primary biliary cirrhosis and primary hepatocellular carcinoma.