ABSTRACT
Objective To explore the dynamic expressions and clinical significance of toll-like receptor 4 (TLR4)/microRNA (miRNA)-181a in the pathogenesis of hepatic fibrosis (HF) in patients with chronic hepatitis B (CHB) .Methods CHB patients underwent liver biopsy for fibrosis staging HF (S) .Real-time polymerase chain reaction (PCR) was used to detect the expressions of miRNA-181a in both serum and liver tissue and the expression of TLR4 mRNA in liver tissue .Western blot was used to detect the expression of TLR4 protein in liver tissue . The fibrosis-4 (FIB-4 ) index and aspartate aminotransferase-to-platelet ratio index (APRI ) were calculated for noninvasive evaluation of fibrosis staging .One-way ANOVA ,Mann-Whitney U test ,spearman correlation analysis and receiver operating characteristic (ROC) curve were used for statistical analysis .Results Forty CHB patients were includedin this study ,including 7 with S0 ,6 with S1 ,14 with S2 ,7 with S3 and 6 with S4 .Serum levesl of miRNA-181a (2-ΔΔCt ) in paitents with S0-4 were 1 .00 ± 0 .00 ,0 .68 ± 0 .08 ,1 .60 ± 0 .43 ,2 .32 ± 0 .40 , and 1 .81 ± 0 .22 ,respectively ,showing an overall upward trend (F=207 .242 ,P< 0 .01) and a positive correlation with the severity of HF (r= 0 .754 , P< 0 .01) .The expressions of miRNA-181a ,TLR4 mRNA and TLR4 protein in liver tissues showed an overall increasing trend from S 0 to S4 (F=207 .242 , 110 .390 and 57 .030 ,respectively ,all P<0 .01) .The expression of miRNA-181a in liver tissue showed a positive correlation with both the expression of TLR4 protein in liver tissue and the severity of HF (r=0 .673 and 0 .911 ,respectively ,both P< 0 .01) .There was no significant difference of APRI scores between the severe (S3-4) and non-severe (S0-2) HF groups (Z= -1 .401 ,P>0 .05) .The serum level of miRNA-181a was superior to FIB-4 index for evaluation of the severe HF (S3-4) ,with areas under the ROC curve (AUROC ) of 0 .887 and 0 .695 , respectively , and accuracy of 85 .0％ and 60 .0％ , respectively .Conclusions miRNA-181a may be involved in the regulation of TLR4 signaling pathway so that to affect the progression of HF in CHB patients ,which may be a potential new target for the prevention and early treatment of HF and a non-invasive serum marker for evaluation of HF .
ABSTRACT
Objective To investigate the distribution of serum hepatitis B surface antigen (HBsAg) levels in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods A total of 226 cases of HBV-related HCC were collected from June 2009 to December 2013.Demographic characteristics of patients with different barcelona clinica liver cancer (BCLC) stages,the status of cirrhosis and HBsAg levels with different virological indicators were compared.HBsAg quantification was tested by chemiluminescence.The statistical analysis was conducted by t test,x2 test,Kruskal-Wallis H rank sum test and Mann-Whitney U rank sum test.Results A total of 226 cases were included with 201male patients and 25 female patients.HBsAg levels in HBV-related HCC patients with different ages were significantly different (x2=12.30,P =0.015),but with no statistical difference in those with different gender (Z=-0.35,P＞0.05).The HBsAg levels were not significantly different between patients with or without liver cirrhosis (Z =-0.80,P =0.419).HBsAg levels in liver cirrhosis cases with different liver function stages were not significant different (x2=2.15,P=0.341).HBsAg levels in HBeAg-positive group or HBV DNA positive group were significantly higher than those in HBeAg-negative group or HBV DNA negative group,respectively (Z =-3.67 and-4.80,respectively,both P＜0.01).The HBsAg levels in patients with different BCLC stages were not significantly different (x2 8.05,P =0.09).No significant differences were found in HBsAg levels between patients with or without portal vein violation,lymph node transfer or distant transfer (Z=-0.65,-0.03 and-1.24,respectively,all P＞ 0.05).The constituent ratios of patients with different HBsAg levels in different BCLC stages were statistically different (x2 =28.17,P-0.005).Conclusions There are no significant differences of HBsAg levels in patients with different BCLC stages,indicating that HBsAg may not be a contributor for disease progression after emergence of HCC.
ABSTRACT
Objective The aim of this prospective observational study was to analyze the prevalence and the predictive factors of hemorrhagic events after abdominal paracentesis in patients with acute-on-chronic liver failure (ACLF).Methods ACLF patients who received at least one episode of abdominal paracentesis were prospectively enrolled between January 2010 to December 2013. Prevalences of intraperitoneal and abdomen hemorrhage complications were examined. t test was performed for continuous variables and chi-square test was performed for categorical variables.Binary Logistic regression was used to analyze the risk factors of hemorrhage.Results A total of 525 abdominal paracenteses were carried out on 185 ACLF patients within a 4-year period,with 289 (55 .0%)for diagnostic purpose and 236 (45 .0%)for therapeutic purpose.A total of 16 (3.0%)hemorrhagic complications were identified, with 4 cases of abdominal wall hematomas and 12 cases of intraperitoneal hemorrhage.Patients were divided into hemorrhage group and non-hemorrhage group according to this complication.Age,gender, Child-Pugh score,volume of ascitic fluid removed,underlying cirrhosis,platelet count and thrombin time were not significantly different between two groups (all P > 0.05 ).Patients with bleeding events had lower fibrinogen levels and higher prothrombin time,international normalized ratio,activated partial thromboplastin time and model for end-stage liver disease score (all P <0.05).After adjustment of other factors,multivariate regression analysis indicated that low fibrinogen level was the only independent predictor of hemorrhagic complication (OR=0.105,95%CI :0.018-0.608,P =0.012).Conclusion Low fibrinogen level is the independent predictor of severe hemorrhagic complications following paracenteses in patients with ACLF.
ABSTRACT
Objective To investigate the relationship between levels of ceruloplasmin (CP) and inflammation grade,fibrosis stages in liver of patients with chronic hepatitis B (CHB),and to establish liver fibrosis non-invasive model and evaluate its diagnostic value for liver pathological stages.Methods Both liver biopsy samples and sera were collected from 148 consecutive CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during January 2009 to June 2011.The relationships between CP and liver pathological stages were analyzed using Spearman rank correlation analysis.Receiver operator characteristic (ROC) curve was used to evaluate the diagnostic value of CP for liver pathological stages.The diagnostic values of relevant indicators were analyzed by Logistic regression.The liver pathology-predicting model was built and the diagnostic value of the model was analyzed by ROC curve.Results The mean values of CP in 148 CHB patients with liver inflammation grades of G1 to G4 were (212.5 ± 34.9),(205.5± 32.0),(201.4 ± 37.7) and (172.8 ± 20.4) mg/L,respectively,which were significantly different by ANOVA test (F=6.309,P＜0.01).Similarly,the mean values of CP in patients with liver fibrosis stages of S1 to S4 were (217.4±32.3),(206.0±37.7),(194.2±29.8) and (179.7±30.4) mg/L,respectively,which were significantly different by ANOVA test (F =8.608,P ＜ 0.01).Spearman rank correlation analysis showed that CP was negatively correlated with liver inflammation grades (r=-0.316,P＜0.01) and fibrosis stages (r=-0.404,P＜0.01).ROC curve analysis revealed that the area under the curves (AUC) were 0.71 (S≥2),0.70 (S≥3) and 0.72 (S=4).Multiple Logistic regression analysis showed that CP,α-fetoprotein,cholesterol,platelet and age were independent predictors for liver fibrosis.ROC curve analysis revealed that AUC were 0.84 in model-1 (S≥2),0.83 in model-2 (S≥3) and 0.87 in model-3 (S=4).The accuracy rates were 71.8％,80.3％ and 79.2％,respectively.Conclusions The CP levels are negatively correlated with inflammation grades and fibrosis stages in the liver of CHB patients.CP could be an important non-invasive indicator for liver fibrosis and the model including CP can be used to predict liver fibrosis in CHB.
ABSTRACT
Objective To investigate the relationship between serum HBeAg level and inflammation grade (G)/fibrosis stage (S) in the liver tissues of chronic hepatitis B (CHB) patients in the immune clearance phase (IC). Methods Both liver biopsy samples and serum samples were consecutively collected from CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during March 2007 to June 2010.Electro-chemiluminescence and fluorogenic quantitative polymerase chain reaction (PCR) methods were used to determine HBeAg titer and hepatitis B virus (HBV) DNA level,respectively.The relationships between HBeAg titer and liver pathological stages were analyzed using Spearman rank correlation analysis.Receive operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBeAg for liver pathological stages.Results Totally 249 patients with CHB were enrolled into this study.The serum HBeAg absorbances in patients with liver inflammation G1 to G4 were (2.93±2.85),(2.96±2.74),(2.69±2.67) and (2.30±2.41) lg s/co,respectively,while those in patients with liver fibrosis S1 to S4 were (2.99±2.74),(2.89±2.73),(2.58±2.55) and (2.32±2.44) lg s/co,respectively,which indicated that serum HBeAg titers were significant different in patients with different grading and staging of liver tissues (x2 =47.13,P＜0.01; x2 =74.12,P＜0.01).Spearman rank correlation analysis showed that serum HBeAg titer was negatively correlated with inflammation grades and fibrosis stages of liver tissues (r=-0.418 and-0.532,respectively; both P＜0.01).ROC curve analysis revealed that the areas under the curve (AUC) were 0.74 (G≥≥3) and 0.73 (G≥4),and the HBeAg (s/co) cut-off values were 2.95 and 2.64 lg s/co,respectively.Similarly,ROC curve analysis revealed that the AUC were 0.80 (S≥3) and 0.77 S≥4),and the HBeAg cut-off values were 2.99 and 2.82 lg s/co,respectively.Conclusions The serum HBeAg titer is negatively correlated with the inflammation grades and fibrosis stages m liver tissues of CHB patients in IC phase.The level of HBeAg may be used as an adjunctive noninvasive marker to reflect the inflammation and fibrosis status in the liver.
ABSTRACT
Objective To study the relationships among the expression of inhibitors of DNA binding 1 (ID-1) , Ki-67 and Bcl-2 in esophageal squamous cell carcinoma (ESCC) ,and to investigate the potential role of ID-1 in the carcinogenesis of ESCC. Methods One hundred and eighteen cases of surgical resected ESCC specimens and 20 cases of normal tissues ( sampled far from the tumors, as control) were involved. Immunohistochemical technique was applied to detect the expression of ID-1, Ki-67 and Bcl-2. Results The positivity and staining intensity of ID-1 , Ki-67 and Bcl-2 in ESCC were higher than those in normal tissues. Positive immunological reactions of ID-1, Ki-67 and Bcl-2 were found in 86.44% (102/118) , 81.36% (96/118) and 59. 32% (70/118) cases of examined tumor samples, respectively. The expression of ID-1 and Bcl-2 were positively correlated with the histological grades, while the Ki-67 expression showed negative correlation with differentiation degree. No relationship was found among age, sex, lymph node metastasis and the expression of ID-1, Ki-67 and Bcl-2 in ESCC tissues. Conclusion ID-1 expression may be participated in the regulation of apoptosis in ESCC cells, but may not be considered as a biomarker for evaluation of ESCC metastasis.