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The microbes and metabolomics of microbiota dysbiosis in the gut in the different phases of hepatitis B virus (HBV) infection are not fully understood.To investigate the specific gut microbiota and metabolites of the immune-tolerant (IT) and immune-active (IA) phases of chronic hepatitis B (CHB).Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were performed.A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla ofThese findings provide observational evidence of compositional alterations of the gut microbiome and some related metabolites in patients with IT-phase or IA-phase HBV infection. Further studies should investigate whether microbiota modulation can facilitate the progression of CHB and the cause-effect relationship between the gut microbiota and CHB.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed an entity by a group of international experts. However, the impact of MAFLD on the prognosis of patients with hepatocellular carcinoma (HCC) is not clear. The aim of this study was to explore the influence of MAFLD for the prognosis of HCC after radical resection.HCC patients who received radical resection were enrolled. The recurrence-free survival (RFS) and overall survival (OS) were compared between MAFLD and non-MAFLD.A total of 576 HCC patients were included, and among them 114 (19.8%) met the diagnostic criteria of MAFLD. The median RFS was 34.0 months in the MAFLD group and 19.0 months in the non-MAFLD group. The RFS rates at 1-, 3-, and 5-year were 64.9%, 49.1% and 36.1% in the MAFLD group, which were higher than those of the non-MAFLD group (59.4%, 35.3% and 26.5%, respectively, P = 0.01). The mean OS was 57.0 months in the MAFLD group and 52.2 months in the non-MAFLD group. There was no statistical difference in OS rate between the MAFLD group and non-MAFLD group. Similar results were found in HBV-related HCC patients in the subgroup analysis. Univariate analysis revealed that MAFLD was a protective factor for RFS in HCC patients after radical resection (P0.05), and there was no association between MAFLD and OS rate (P0.05). Multivariate analysis demonstrated that MAFLD was not an independent protective factor for HCC patients with radical resection.MAFLD improves RFS rate in HCC patients with radical resection, but is not an independent protective factor and not associated with OS rate.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer, with high rates of morbidity and mortality, a poor prognosis and limited therapeutic options. The objective of the present study was to demonstrate the anticancer activity of oleanolic acid in HepG2 human HCC cells. Cell viability was evaluated using an MTT assay, following administration of various doses of oleanolic acid. The effect of oleanolic acid on cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry with propidium iodide and rhodamine-123 DNA-binding cationic fluorescent dyes. Fluorescence microscopy was employed to detect morphological changes in HepG2 cells following oleanolic acid treatment. The results revealed that oleanolic acid induced a dose-dependent, as well as time-dependent inhibition in the growth of HepG2 cancer cells. Following acridine orange and ethidium bromide staining, treatment with various doses (0, 5, 25 and 50 µM) of oleanolic acid induced typical morphological changes associated with apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation. Cell cycle analysis revealed that oleanolic acid induced cell cycle arrest in HepG2 cells at the sub-G1 (apoptotic) phase of the cell cycle, in a dose-dependent manner. Staining with Annexin V-fluorescein isothiocyanate and propidium iodide revealed that apoptosis occurred early in these cells. Oleanolic acid treatment also resulted in fragmentation of nuclear DNA in a dose-dependent manner, producing the typical features of DNA laddering on an agarose gel. The results also demonstrated that oleanolic acid treatment resulted in a potent loss of mitochondrial membrane potential, which also occurred in a dose-dependent manner. Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC.

Acute liver failure (ALF) is associated with high mortality. Gasdermin D (GSDMD) is the executioner of pyroptosis and is involved in the pathophysiology of immune dysregulation This study investigated the role of the GSDMD inhibitor necrosulfonamide (NSA) in ALF.An ALF model was established by lipopolysaccharide/D-galactosamine challenge in C57BL/6J mice. Mice were divided into four groups: normal controls (control group), ALF group (ALF group), dimethyl sulfoxide group (DMSO group), and NSA intervention group (NSA group). Survival was monitored, liver damage was determined by hematoxylin and eosin staining, and serum alanine aminotransferase (ALT). Underlying mechanisms were explored by quantitative real-time PCR, western blotting, and enzyme-linked immunosorbent assays.Pyroptosis was activated in ALF model mice. Mice treated with GSDMD inhibitor NSA developed less severe liver failure. NSA reduced the expression of GSDMD, NLRP3, cleaved caspase-1, cleaved caspase-11, and secretion of interleukin-1 beta in ALF mice model.Pyroptosis was activated in ALF. NSA alleviated ALF via the pyroptosis pathway.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer, with high rates of morbidity and mortality, a poor prognosis and limited therapeutic options. The objective of the present study was to demonstrate the anticancer activity of oleanolic acid in HepG2 human HCC cells. Cell viability was evaluated using an MTT assay, following administration of various doses of oleanolic acid. The effect of oleanolic acid on cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry with propidium iodide and rhodamine‑123 DNA‑binding cationic fluorescent dyes. Fluorescence microscopy was employed to detect morphological changes in HepG2 cells following oleanolic acid treatment. The results revealed that oleanolic acid induced a dose‑dependent, as well as time‑dependent inhibition in the growth of HepG2 cancer cells. Following acridine orange and ethidium bromide staining, treatment with various doses (0, 5, 25 and 50 µM) of oleanolic acid induced typical morphological changes associated with apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation. Cell cycle analysis revealed that oleanolic acid induced cell cycle arrest in HepG2 cells at the sub‑G1 (apoptotic) phase of the cell cycle, in a dose‑dependent manner. Staining with Annexin V‑fluorescein isothiocyanate and propidium iodide revealed that apoptosis occurred early in these cells. Oleanolic acid treatment also resulted in fragmentation of nuclear DNA in a dose‑dependent manner, producing the typical features of DNA laddering on an agarose gel. The results also demonstrated that oleanolic acid treatment resulted in a potent loss of mitochondrial membrane potential, which also occurred in a dose‑dependent manner. Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC.

Summary Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3–4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.

Objective Multiple biliary hamartomas (MBHs) are rare benign malformations of the intrahepatic bile ducts. There are only a handful of clinical studies based on large populations on the incidence of MBHs. Materials and methods A series of 1697 consecutive liver needle biopsies was examined for the occurrence of MBHs. Results A total of six patients (0.35%, four men and two women, a 2 : 1 ratio) were confirmed by histology to have MBHs. Of the total of 1697 patients, 59 (3.5%) patients were younger than 18 years of age, 828 patients (48.8%) were between 18 and 38 years of age, and 810 patients (47.7%) were older than 38 years of age. Of the six MBHs patients, one was 17 years of age and the other five patients were older than 39 years of age. The median (range) age of the patients was 42 (17-63) years. Although nearly half (48.8%) of the biopsied patients were between 18 and 38 years of age, no MBH was found in this group. All MBHs patients were diagnosed with fibrosis/cirrhosis by initial ultrasound scanning; however, only two patients were confirmed to have cirrhosis by histological examination. Of those two patients with cirrhosis, one had concomitant congenital hepatic fibrosis and the other had concomitant cirrhotic hepatitis B. The latter patient developed hepatocellular carcinoma 1 year after biopsy. No kidney cysts were found in any of the six MBHs patients. MRI scanning was performed in four patients and the results were consistent with the histological diagnosis. Conclusion MBHs are not common in patients who undergo liver biopsy and, in this study, the occurrence was higher in the older age group.

Enoyl-coenzyme A hydratase (ECHS1) is a key enzyme in the metabolism of fatty acids in mitochondria. We previously reported that hepatitis B surface antigen (HBsAg) interacted with ECHS1 in a yeast two-hybrid system. In the current study, we further examined their interaction by using GST pull-down and co-immunoprecipitation assays. The results confirmed that small hepatitis B surface antigen (SHBs) interacted with ECHS1. Furthermore, confocal imaging showed that SHBs and ECHS1 co-localized in HepG2 cells. To clarify the biological function of the interaction, human hepatoma cell lines that transiently and stably expressed SHBs were generated. The expression of SHBs led to a significant decrease in ECHS1 protein levels. ECHS1 protein levels were reduced to 48.44 ± 7.12 % in Huh7 cells transiently expressing SHBs, and to 54.97 ± 3.54 % in HepG2 cells stably expressing SHBs. In conclusion, our findings suggest that SHBs interacts with ECHS1 and regulates ECHS1 protein levels in hepatoma cells.

Supplemental Digital Content is available in the text, To investigate changes in the HBV replication level along with the natural course of chronic HBV infection and to examine the accuracy of the immune tolerant phase defined by the serological profile. A total of 390 chronic HBV-infected patients were retrospectively recruited for this study. They were classified into immune-tolerance (IT), immune-clearance (IC), low-replicative (LR), and HBeAg-negative hepatitis (ENH) phases according to serological profiles (single-standard, SS) or dual-standard (DS) with the inclusion of liver histology. Serum HBV DNA and HBsAg were quantitatively measured, and liver histology was quantitatively analyzed. The accuracy of the SS-defined IT phase was low, and active pathological changes were detected in 56 of 112 SS-defined IT patients. DS-defined IT patients had higher HBsAg levels (P = 0.0002) than the SS-defined patients. The quantitative HBsAg level can help identify SS-defined IT patients with potential liver injury. The area under the received operating characteristic curve for predicting the DS-defined IT phase was 0.831 (HBsAg 4.398 log IU/mL; sensitivity 87.5%; specificity 73.2%). HBV DNA was reduced by 4 logs, whereas HBsAg was only decreased by 2 logs with HBeAg positive to negative phase conversion. Approximately half of IT patients defined by SS may have medium or severe liver injury. Quantitative measurement of the HBsAg level can help identify SS-defined IT patients with potential liver injury.

To investigate the prevalence and characteristics of hepatitis B e antigen (HBeAg) negative/treatment naïve subjects with low hepatitis B virus (HBV) DNA levels (10(4) copies/ml) and low alanine aminotransferase (ALT) levels (2 × upper limit of normal) in patients with HBV-related hepatocellular carcinoma (HCC).A total of 226 treatment naïve patients diagnosed with HBV-related HCC, divided into five Barcelona Clinic Liver Cancer (BCLC) stages, were enrolled and retrospectively analyzed. Virological parameters including hepatitis B surface antigen (HBsAg), HBeAg, HBV DNA levels, and laboratory parameters including ALT and aspartame aminotransferase were accessed at the time of HCC was diagnosed. Comparison between HBeAg positive patients and HBeAg negative patients was performed using a χ(2) test.While laboratory parameters correlated with BCLC stages, virological parameters did not. HBeAg negative patients were more prevalent than HBeAg positive patients (160, 70.8% vs. 66, 29.2%). HBsAg and HBV DNA levels in HBeAg negative patients were significantly lower than that in HBeAg positive patients (all P 0.001). Of the 160 HBeAg negative patients, 74 (46.25%) had low HBsAg, 76 (47.5%) had low DNA levels, and 35 (21.9%) patients had low DNA and normal ALT levels.In treatment naïve patients with HBV-related HCC, the majority (70.8%) were HBeAg negative patients. More than one fifth of HBeAg negative patients had low HBV DNA levels and normal ALT levels, indicating more strict monitoring for HBeAg negative patients is needed.

Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue (NA) therapy and the impact of these changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and cccDNA via real-time fluorescent PCR. In situ detection of CD4(+) , CD8(+) T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV-specific IFN-γ-producing CD4(+) T cells in patients with HBeAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8(+) T lymphocytes increased in patients with HBeAg loss compared with baseline values. Only one patient without HBeAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV-DNA decline, which could promote the recovery of antiviral immunity and facilitate HBeAg loss.

The association between hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) levels and liver inflammation and fibrosis in patients with chronic hepatitis B (CHB) in the immune clearance (IC) remains elusive. The aim of the present study was to investigate whether HBsAg and HBeAg levels were associated with liver inflammation and fibrosis in CHB patients during the IC phase. Kendall's rank correlation analysis and receiver operating characteristic curves were used to determine the correlation between HBsAg, HBeAg and liver pathological stages. Multivariate analysis by forward logistic regression was used to analyze significant predictors of cirrhosis. A liver pathology‑predicting model (IC model), which used routinely assessed markers in combination with HBsAg and HBeAg levels, was constructed. There were significantly positive correlations between the HBsAg and HBeAg levels (γ=0.317, P

To investigate the influence of hepatitis B virus (HBV)-encoded small surface protein (SHBs) on hepatic cell expression of host genes related to lipid metabolism.The full-length SHBs gene was amplified from HBV genotype C by polymerase chain reaction (PCR) and cloned into the pcDNA3.1(+) expression vector for stable transfection into HepG2 cells (selected by G418 screening); cells transfected with empty vector served as control. The SHBs mRNA and protein levels were detected by reverse transcription-PCR and enzyme-linked immunosorbent assay. SHBs effects on expression of genes and proteins related to lipid metabolism were detected by real-time quantitative (q)PCR and western blotting, respectively.The stably transfected cell line HepG2-pn3.1-SHBs was established successfully. qPCR showed that the HepG2-pn3.1-SHBs cells had significantly down-regulated transcription of the ECHS1, APOA1 and LPL genes (0.161+/-0.043 vs. control cells: 0.210+/-0.022, t = 2.479; 0.031+/-0.007 vs. 0.094+/-0.055, t = 2.752; 0.770+/-0.036 vs. 0.982+/-0.031, t = 10.914), but significantly up-regulated ACC and SREBP-1c genes (0.113+/-0.027 vs. 0.059+/-0.022, t = -3.757; 0.019+/-0.002 vs. 0.015+/-0.001, t = -4.330). The CPT1a and PPARa genes' expression was slightly, but not significantly, down-regulated in the HepG2-pn3.1-SHBs cells (0.028+/-0.005 vs. 0.030+/-0.004, t = 1.022; 0.014+/-0.004 vs. 0.015+/-0.002, t = 0.758). Western blotting showed similar expression trends for the corresponding proteins.SHBs alters the expression of some host genes with known functions in fatty acid synthesis and decomposition; however, it remains unclear whether the hepatitis B surface antigen can directly contribute to development of hepatic steatosis.

To observe the changes in hepatitis B virus (HBV)-specific and non-specific cellular immunity that accompany viral load decline during adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, and to explore the antiviral immunity mechanism underlying the treatment response.Serial analysis of cellular immunological parameters was performed in HBeAg-positive patients (n = 20) throughout the 48-week course of ADV therapy (10 mg/d). HBV-specific T cell reactivity to HBV core antigen (HBcAg) was assessed by enzyme-linked immunosorbent spot assay and cell proliferation assay at pre-treatment (baseline) and post-treatment weeks 4, 12, 24, 36, and 48. Percentage of regulatory T cells (Tregs), as well as activated peripheral natural killer (NK) cells (expressing the NKG2D receptor), was measured by flow cytometry. Comparisons of means were performed by the two-tailed t-test or the Mann-Whitney rank sum test.After 48 weeks of ADV therapy, HBeAg loss was observed in six of the 20 (30%) patients and 14 patients remained HBeAg-positive. In the patients with HBeAg loss, the viral load reduction was accompanied by a significantly enhanced response rate of HBV-specific interferon (IFN)-gamma-producing CD4+ T cells [measured as (spot forming cells/peripheral blood mononuclear cells); baseline: (661.25+/-281.97) *10(-6) vs. week 48: (280.75+/-104.33) *10(-6), P = 0.045]. In contrast, patients without HBeAg loss showed no significant differences in T cell response rates. The patient groups with and without HBeAg loss showed similar proportions of peripheral blood Tregs during the treatment course, which included a trend of gradual decrease from baseline to week 4 with steady levels thereafter. In addition, both groups showed a similar increase in NKG2D expression that began at week 12 and peaked at week 48.HBV-specific T cell reactivity temporally increases in some ADV-treated chronic hepatitis B patients, and this trend is strongly associated with HBeAg loss. Furthermore, recovery of HBV-specific T cell reactivity promotes viral clearance and HBeAg seroconversion.

Hepatitis B e antigen (HBeAg) seroconversion and/or hepatitis B surface antigen (HBsAg) clearance are considered as good prognostic indicators of treatment outcome in HBeAg-positive chronic hepatitis B (CHB) patients. While a sustained virological response (SVR) can be achieved by a finite 48-week course of pegylated-interferon alfa-2a (Peg-IFNalpha-2a), it has been suggested that longer-term treatment can improve the rate of SVR. Therefore, the aim of this study was to compare the effects of prolonged and routine Peg-IFNa-2a therapy in patients with HBeAg-positive CHB.Eighty-six consecutive patients diagnosed with HBeAg-positive CHB at our hospital between September 2006 and October 2009 were enrolled in the study. The patients were randomly assigned to receive Peg-IFNa-2a (180 mug once weekly) for either 48 weeks (routine therapy group, n = 53) or 72 weeks (prolonged therapy group, n = 33). Serum samples were collected from each patient every three months until the end of the 24-week follow-up, and standard viral and biochemical tests were carried out. Relapse was defined as HBV DNA concentrations more than 105 copies/mL or an HBeAg-positive test at the end of the 24-week follow-up. Chi-squared test and the t-test were used to determine the significance of intergroup differences. Logistic regression analysis was employed to determine the correlation of outcome parameters to treatment duration, expressed as odds ratio (OR) with 95% confidence interval (CI).The two treatment groups were similar at baseline (pre-treatment) in demographic data, sex ratio, age, alanine aminotransferase (ALT) level, HBV DNA load, and semi-quantitative level of HBeAg (s/co) (all, P more than 0.05). At the end of the 24-week follow-up, there were significant differences between the 48-week treatment group and the 72-week treatment group in patients with HBV DNA negativity (62.3% vs. 97.0%, x2 = 13.273, P = 0.000), HBeAg seroconversion (39.6% vs. 57.6%, x2 = 6.765, P = 0.009), HBsAg clearance (15.1% vs. 36.4%, x2 = 5.155, P = 0.023), and relapse (58.5% vs. 33.3%, x2 = 6.713, P = 0.010). Logistic regression analysis indicated that therapy duration was correlated to HBeAg clearance (OR = 3.702, 95% CI: 1.225 to 11.188) and male sex (OR = 3.005, 95% CI: 1.038 to 8.696) but not to HBeAg level at baseline (OR = 0.999, 95% CI: 0.998 to 1.000) or age (OR = 0.902, 95% CI: 0.839 to 0.970).In this single-center cohort study, superior therapeutic benefit was achieved by extending the Peg-IFNa-2a therapy out to 72 weeks for patients with HBeAg-positive CHB. The prolonged duration therapy produced a higher HBsAg loss ratio, HBeAg seroconversion ratio, HBV DNA negativity ratio, and a lower relapse ratio. Furthermore, HBeAg clearance was positively correlated with duration and male sex.

To investigate whether the level of hepatitis B surface antigen (HBsAg) represents the status of inflammation and stages of fibrosis in livers of patients with chronic hepatitis B (CHB) during the immune clearance phase (IC).Liver biopsy samples and sera were collected from 165 consecutive patients (136 males; 29 females) with CHB in IC who were treated in our hospital between March 2009 and June 2011. Routine biochemical tests were carried out to measure indicators of liver function. The relation between HBsAg level and liver pathological stages were determined by Spearman's rank correlation analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBsAg level for liver pathological stages. Binary logistic regression was used to analyze potentially relevant indicators, and liver pathology-predicting models were built and analyzed by the ROC method.The mean values of HBsAg (IU/mL) were significantly different at the different liver inflammation stages: G1, 27 716.07+/-32 870.69; G2, 34 478.75+/-40 899.55; G3, 19 408.09+/-24 881.07; G4, 14 286.31+/-28 610.14. Likewise, the mean values of HBsAg (IU/mL) were significantly different at the different liver fibrosis stages: S1, 41 337.23+/-43 236.39; S2, 27 264.32+/-32 517.29; S3, 111 541.77+/-11 538.93; S4, 11 447.37+/-22215.44. Spearman's rank correlation analysis indicated a significant correlation between HBsAg level and liver inflammation stage (rs = -0.244) and fibrosis stage (rs = -0.365). ROC curve analysis of the diagnostic value of HBsAg for inflammation stages S more than or equal to 4 revealed that the area under the curve (AUC) was 0.70. The specificity of diagnosing S more than or equal to 4 was95.16% when HBsAg was less than or equal to 32995 IU/mL. Binary logistic regression analysis identified age, serum albumin, cholinesterase, and HBsAg as independent predictors of liver fibrosis.HBsAg level is negatively correlated with liver inflammation and fibrosis stages for patients with CHB in the IC phase, and might represent a useful noninvasive marker of the degree of hepatic fibrosis.

Background The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. Methods We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. Results Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64-0.94), 0.91 (95% CI, 0.80-0.96) and 52.89 (95% CI, 15.21-183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13-19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07-0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92-0.96). Conclusion This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis.

AbstarctPatients with acute on chronic liver failure (ACLF) usually present with severe coagulopathy. Abdominal paracentesis is often performed in these patients. The aim of this study was to analyze the prevalence of hemorrhagic events after paracentesis and the predictive factors of this condition

To build a mathematical model for diagnosing liver fibrosis progression by using conventional laboratory indicators, and to evaluate its clinical value of predicting hepatic fibrosis and hepatocirrhosis in chronic hepatitis B.Liver biopsy and routine laboratory tests were performed in 391 patients with chronic hepatitis B. Using Multiple logistic regression to analyse evidently relevant indicators,then the models predicting for different stages of liver fibrosis were built and analyzed by receiver operating characteristic (ROC) curve.Age, platelet (PLT), international rate (INR), total bilirubin, albumin (ALB), aspartate aminotransferase, gamma-glutamyltranspeptidase (GGT), total bile acid and cholinesterase (CHE) were correlated with liver fibrosis stage. Multiple Logistic regression analysis showed that PLT, INR, ALB, GGT and CHE were independent predictors of three models ( Sor = 2, Sor = 3, S = 4). We finally built the predicting models and got Fibrosis scores (FS). ROC curve analysis revealed that the area under the curve was 0.784 in model-1 (Sor = 2), 0.768 in model-2 (Sor = 3) and 0.806 in model-3 (S = 4). A FS, cutoff point of 7.09 had 67.4% sensitivity, 79.3% specificity and 71.1% accuracy in Model-1. A FS2 cutoff point of 5.67 had 75.0% sensitivity, 67.7% specificity and 72.9% accuracy in Model-2. A FS3 cutoff point of 3.65 had 71.4% sensitivity, 78.5% specificity and 73.7% accuracy in Model-3.The mathematical models using conventional laboratory indicators have fairly well value for predicting hepatic fibrosis progressing in chronic hepatitis B.

This study was aimed to investigate the inhibitory effect of combined transfection of p53 and angiostatin (AS) genes on K562 cells and to explore its mechanism. pVTRIO2-hp53-hAS was transfected into K562 cells with lipofectamine 2000, RT-PCR was used to determine the expression of gene of interest in transfected cells, MTT growth curve and flow cytometry were used to analyze the cell cycle for observation biological changes of cells, the cellular immunochemistry assay was used to observe the expression differences between VEGF, Bcl-2 and Bax proteins. The results indicated that the genes of interest have been transfected and stably expressed, the increase of K562 with genes of interest was slower than that without genes of interest (p0.05). And the increase of K562 in double gene group was slower than that in p53 and AS groups (0.264+/-0.011 at last day A290 nm; 0.652+/-0.039 at last day A290 nm; 0.604+/-0.017 at last day A290 nm respectively) (p0.05). After transfection, the expressions of VEGF and Bcl-2 protein decreased, but the expressions of Bax increased. It is concluded that the combined transfection of p53 and AS genes into K562 cells shows more notable and powerful inhibition on proliferation than those transfected with single one gene. The synergistic mechanism of p53 and AS genes may be commonly influenced the pathway of Bcl-2 and Bax expression.

To explore the effects of vascular endothelial growth factor (VEGF) on the mechanisms of CML pathogenesis, the effect of VEGF on K562 cell apoptosis induced by As(2)O(3) was analyzed through morphologic observation, DNA fragmentation agarose gel electrophoresis and DNA ploidy flow cytometry analysis, and the effect of VEGF on the expression of bcl-X(L), Bax and caspase-3 in K562 cells was determined by Western blot, meanwhile the expression difference between bcl-X(L) and Bax mRNA in above conditions was detected by RT-PCR. The results showed that after VEGF added, the apoptosis of K562 cells reduced, however, there was no significant changes in cell cycle distribution (P0.05). At the same time, following the increasing of the concentration of VEGF, expression of mRNA and protein of bcl-X(L) was up-regulated and the expression of Bax protein was down-regulated in K562 cells, and the activation of pro-caspase-3 into caspase-3 was inhibited or reduced. It is concluded that VEGF may suppress the apoptosis of K562 cells through its influence on the bcl-X(L)/Bax expression ratio in K562 cells.

To investigate the association between heat shock protein 70-hom (HSP70-hom) gene polymorphism and ankylosing spondylitis(AS) in Chinese Han patients.Genomic DNA from 98 Chinese AS patients and 70 ethnically matched controls were typed for HSP70-hom polymorphism by polymerase chain reaction-restriction fragment length polymorphism.The HSP70-hom genotypes in the AS patients consisted of homozygote AA (60.2%) and BB(4.1%), and heterozygote(35.7%), while the HSP70-hom genotypes in the controls were composed of AA(58.6%), BB(2.9%) and heterozygote(38.6%). No significant difference was found in the distribution of HSP70-hom genotype between these two groups(chi(2) test=0.280, P0.05). The frequencies of HSP70-hom alleles in AS patients were 77.9%(AA) and 22.1%(BB), while they were 78.1% and 21.9% in the controls. The frequency of HSP70-hom allele in AS patients was not significantly increased, compared with that in controls (chi(2) test=0.002, P0.05).There may be no association between the HSP70-hom gene polymorphism and ankylosing spondylitis in Chinese Han population.