KIF18B promotes hepatocellular carcinoma progression through activating Wnt/ß-catenin-signaling pathway.

This study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The χ2 test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor-node-metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/ß-catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/ß-catenin-signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/ß-catenin pathway.

Contribution of endotoxin to Th17 bias in patients with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) with more severe inflammation-induced liver damage. Microbial products, such as endotoxin, may contribute to the pathogenesis of NASH. In this study, we investigated the effect of serum endotoxin on CD4 T cell inflammation. Age and sex-matched non-obese healthy subjects, subjects with non-alcoholic fatty liver (NAFL) but not steatohepatitis, and NASH patients were recruited for this study. The latter two groups were additionally matched in BMI and diabetes status. We first showed that compared to healthy subjects and NAFL patients, NASH patients presented significantly higher levels of serum endotoxin. Concurrently, NASH patients presented a Th17 bias that was associated with high endotoxin levels. To examine whether endotoxin could directly mediate IL-17 expression from CD4 T cells, naive CD4 T cells were stimulated with varying levels of endotoxin. In healthy subjects and NAFL patients, endotoxin did not act directly on naive CD4 T cells but required the presence of antigen-presenting cells to upregulate IL-17. Inhibition of TLR4 in macrophages, but not in CD4 T cells, could impair endotoxin-mediated IL-17 upregulation. In NASH patients, however, endotoxin at high levels directly, but minimally, increased IL-17 production. We further found that naive CD4 T cells from NASH patients presented significantly higher TLR4 than naive CD4 T cells from healthy subjects and NAFL patients, and CD3/CD28 stimulation could significantly elevate TLR4 expression by naive CD4 T cells. Overall, these data demonstrate that endotoxin promote Th17 bias in NASH patients.

Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases.

OBJECTIVE: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined. MATERIALS AND METHODS: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis. RESULTS: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF patients within six months after the disease onset (OR 1.704, p = .041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p < .001), while C1913A led to a significant decrease of core protein expression (p < .05). CONCLUSION: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.

Reactivity toward Bifidobacterium longum and Enterococcus hirae demonstrate robust CD8+ T cell response and better prognosis in HBV-related hepatocellular carcinoma.

Recent studies suggest that several bacterial species are involved in tumor immunosurveillance and antitumor immunity. The role of bacteria in immune responses in HBV-related hepatocellular carcinoma (HCC) patients is still unknown. In this study, we examined the bacteria-reactive CD8+ T cell response in patients with HBV-related HCC. We found that circulating CD8+ T cells from healthy individuals demonstrated minimal or zero specificity toward a series of commensals and bacteria previously associated with antitumor effects, including Escherichia coli, Enterococcus faecium, Bifidobacterium longum, Bacteroides fragilis, and Enterococcus hirae. In contrast, the circulating CD8+ T cells from HBV-related HCC patients presented significantly elevated bacteria-reactive responses, albeit with high variations among different HCC individuals. Reactivity toward bacteria was also identified in tumor-infiltrating CD8+ T cells. These bacteria-reactive responses were not primarily induced by TLR ligand, but were dependent on the presence of antigen-presenting monocytes, and were MHC class I-restricted. Interestingly, we observed that the CD8+ T cell-to-Foxp3+ regulatory T cell ratio was positively correlated with the proportions of Bifidobacterium longum-reactive and Enterococcus hirae-reactive CD8+ T cells, while the frequency of PD-1+ CD8+ T cells was negatively correlated with the frequency of Enterococcus hirae-reactive CD8+ T cells. Furthermore, the disease-free survival time of HCC patients after tumor resection was positively correlated with the frequencies of Bifidobacterium longum-reactive and Enterococcus hirae-reactive CD8+ T cells. Together, these results suggested that certain bacterial species might present valuable antitumor effects.

[Clinical characteristics of 4132 patients with alcoholic liver disease].

OBJECTIVE: To study the clinical characteristics of patients with alcoholic liver disease (ALD). METHODS: The records of the 302 Hospital of People's Liberation Army (Beijing, China) were searched to identify patients diagnosed with liver disease for retrospective analysis of ALD. Measurement data was summarized as mean +/- standard deviation and intergroup comparisons were made using ANOVA; count data was assessed using the chi-square test. RESULTS: Among the total 4132 ALD cases, 97.68% were male and 2.32% were female; ages ranged from 18 to 95 years-old,with the average age being 48.11+/-10.58 years and the range of 40 to 60 years-old being the most frequently represented.Considering all patients with liver disease from 2003 to 2012,ALD cases increased over time (from 2.00% in 2003 to 5.05% in 2012). The overall ALD cases were represented by alcoholic cirrhosis (70.35%), alcoholic hepatitis (19.26%), alcoholic fatty liver (6.29%), and alcoholic liver failure (4.09%). Among the ALD patients between 40 and 60 years of age, 73.81% had cirrhosis,compared to 50.42% of ALD patients less than 40 years-old (P less than 0.001). Comparison of ALD cases in 5-year increments showed increasing trends in rates of alcoholic cirrhosis and alcoholic hepatic failure;moreover, there was an increasing annual trend in the percentage of alcoholic liver failure cases among the total cases of liver failure in our hospital. CONCLUSION: From 2003 to 2012,our hospital admissions increased for patients with alcoholic liver disease, and the patients were primarily in the age range of 40-60 years-old. In general, incidences of alcoholic liver failure and cirrhosis increased in recent years, and cirrhosis has been common among the elderly patients with ALD.

Safety of Human Hepatoma Cell-Line Constructing Bioartificial Liver Supporting System Treating Patients with Liver Failure.

BACKGROUND/AIMS: To observe the clinical safety of bioartificial liver supporting system constructed by human hepatoma cell line. METHODOLOGY: Seventeen patients with liver failure were treated with C3A-cell-constructed bioartificial liver supporting system, contrasting the difference of biochemical results and imaging data with 9 patients treated with non-bioartificial liver during 5-year treatment. RESULTS: 11 cases of Treatment Group survived at 3 months' follow-up, among whom 2 cases underwent hepatic transplantation. 9 cases without hepatic transplantation survived in 5-year follow-up, and 1 of them was found to occur focal liver lesion at the 5th years, and had hepatic lobectomy. Pathological prompt: hepatocellular carcinoma with moderate differentiation. Totally 4 patients in Control Group survived after 3 months' follow-up, including 1 patient of hepatic transplantation. All the 3 patients without hepatic transplantation survived the last 5-year follow-up, with basically normal biochemical indicators and no focal liver lesion were found by imaging examination. CONCLUSIONS: It was safe to use bioartificial liver constructed by tumor cell line C3A to treat liver failure.

CD34+ hematopoietic stem cells mobilization, paralleled with multiple cytokines elevated in patients with HBV-related acute-on-chronic liver failure.

BACKGROUND: Recent studies indicate that bone marrow (BM)-derived stem cells contribute to liver regeneration. But limited information is available on the dynamic and mechanisms of mobilization of BM-derived hematopoietic stem cells (HSCs) after acute-on-chronic liver failure (ACLF). AIMS: The purpose of this study was to assess the mobilization of BM-derived CD34+ HSCs in ACLF patients, and elucidate the association of stress-induced cytokines in HSCs mobilization and/or liver repair in ACLF patients. METHODS: Thirty patients with HBV-related ACLF, 30 patients undergoing chronic hepatitis B, and 20 healthy controls were enrolled. The percentages of peripheral blood CD34+ cells were determined by two-color flow cytometry. The hepatic commitment of mobilized CD34+ cells was investigated by RT-PCR. The serum levels of stress-induced cytokines were determined by enzyme-linked immunosorbent assays. RESULTS: A significant increase of circulating CD34+ cells was observed in ACLF patients. RT-PCR analyses showed that the mobilized CD34+ cells expressed both CD34 mRNA and liver-specific markers including cytokeratin 19 and α-fetoprotein. In parallel with mobilization of BM-derived CD34+ cells, elevated serum levels of hepatocyte growth factor, interleukin-6, stem cell factor, granulocyte colony-stimulating factor and matrix metalloproteinase 9 were observed in ACLF patients. CONCLUSION: We demonstrated that ACLF led to mobilization of CD34+ cells, which had a hepatic differentiation potential.

Clinical analysis of bacterial infection characteristics in lymphoma patients with high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation-a single-centered retrospective study.

BACKGROUND: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation. OBJECTIVE: To characterise pathogenic bacterial infections in HDT/AHSCT-treated lymphoma patients. The prevalence of pathogenic microorganisms and the timing of foci after transplantation, along with bloodstream infection (BSI) risk factors, can help determine the need for empirical antibiotics after AHSCT. METHODS: We retrospectively analyzed 133 lymphoma patients treated by HDT/AHSCT from April 2017 to October 2021 at Peking University International Hospital, Beijing, China. We analyzed their clinical characteristics, microbiological distribution characteristics, and BSI risk factors in detail. RESULTS: In order, intestinal infection (56 cases), BSI (17 cases), pulmonary (12 cases), upper respiratory tract (5 cases), and perianal (4 cases) were the most common locations of infection after HDT/AHSCT. The infection sites yielded 92 putative pathogenic pathogens, with bacteria predominating (61.96%), fungi (28.26%), viruses (5.43%), and mycoplasma (4.35%). Gram-negative bacteria (GNB) strains outnumbered gram-positive bacteria (GPB) strains (73.68%). Two strains of Escherichia coli produced extended-spectrum ß-lactamase (ESBL) and one strain of carbapenem-resistant enterobacteriaceae (CRE). Methicillin-resistant Staphylococcus epidermidis (MRSE) had one strain. BSI was caused by Escherichia coli (82.35%), Intestinal mucositis (23.52%), and catheter-associated infections (11.76%). Age, CD34, pretreatment regimen, antibiotic regimen, and past chemotherapeutic agent lung damage were BSI risk variables in univariate analysis. CD34 and past chemotherapeutic drug lung damage were the primary causes of BSI after HDT/AHSCT for lymphoma. CONCLUSION: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.

[Clinical and pathological analysis of 566 patients with cryptogenic liver diseases].

OBJECTIVE: To investigate the etiology, pathology, and clinical characteristics of cryptogenic liver diseases in order to develop a pathogenic profile for clinical diagnosis and therapeutic design. METHODS: The data of the 566 patients diagnosed with abnormal liver function and who had undergone liver biopsy at our institute between January 2006 to March 2010 were retrospectively analyzed. The Chi-squared (x²) test was used to assess disease correlation with sex and the rank sum test was used to assess disease correlation with continuous data since all data had asymmetric distribution. RESULTS: Among the 566 patients, abnormal liver function was attributed to alcoholic liver disease (n=175; 30.92%), drug-induced or environmentally-induced liver disease (n=101; 17.84%), hereditary and metabolic disease (n=93; 16.43%), infectious hepatitis disease (n=84; 14.84%), fatty liver disease (n=53; 9.36%), and autoimmune liver disease (n=30; 53.00%). Thirty patients had unknown etiology, despite liver biopsy analysis. Among these disease subgroups, there were distinct correlations with sex, age, and levels of alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The autoimmune liver disease group was correlated with sex (q=9.14, 7.435, 5.071, 9.529, and 12.5, respectively; P less than or equal to 0.01). The alcoholic liver disease group and autoimmune liver disease group were correlated with age (vs. genetic metabolic disease group: q=17.254 and 10.302; infectious hepatitis group: q=17.523 and 10.697); drug/environmentally-induced liver damage group: q=9.170 and 5.266); fatty liver group: q=7.118 and 4.661) (P less than or equal to 0.01). In addition, the alcoholic and autoimmune liver disease groups were correlated with GGT levels (vs. genetic metabolic disease group: q=8.003; infectious hepatitis group: q=4.793; drug/environmentally-induced liver damage group: q=4.404) (P less than or equal to 0.01). CONCLUSION: Liver pathology is important for the diagnosis of cryptogenic liver diseases. Patient age, sex, and biochemistry index may facilitate diagnosis and treatment in the absence of pathology.

Multiomic analysis of the function of SPOCK1 across cancers: an integrated bioinformatics approach.

OBJECTIVE: To investigate SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1 (SPOCK1) gene expression across The Cancer Genome Atlas (TCGA) cancers, both in cancer versus normal tissues and in different stages across the cancer types. METHODS: This integrated bioinformatics study used data from several bioinformatics databases (Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, TCGA, Tumor Immune Estimation Resource [TIMER]) to define the expression pattern of the SPOCK1 gene. A survival analysis was undertaken across the cancers. The search tool for retrieval of interacting genes (STRING) database was used to identify proteins that interacted with SPOCK1. Gene Set Enrichment Analysis was conducted to determine pathway enrichment. The TIMER database was used to explore the correlation between SPOCK1 and immune cell infiltration. RESULTS: This multiomic analysis showed that the SPOCK1 gene was expressed differently between normal tissues and tumours in several cancers and that it was involved in cancer progression. The overexpression of the SPOCK1 gene was associated with poor clinical outcomes. Analysis of gene expression and tumour-infiltrating immune cells showed that SPOCK1 correlated with several immune cells across cancers. CONCLUSIONS: This research showed that SPOCK1 might serve as a new target for several cancer therapies in the future.

A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure.

The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents.

Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial-mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3'-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo.

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl4 also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 µg/mL effectively relieved CCl4-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl4 treatment. The high serum ALT and AST levels induced by CCl4 were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl4-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl4-induced liver damage.

CXCR5+ CD8+ T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection.

Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5+ CD8+ T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5+ CD8+ T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5+ CD8+ T cells in peripheral blood, in which CXCR5+ CD8+ T cells were negatively correlated with the frequency of CXCR5+ CD4+ T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5+ CD8+ T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5- CD8+ T cells. Unlike CXCR5+ CD4+ T cells, when incubated with naive CD19+CD27- B cells, CXCR5+ CD8+ T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5+ CD8+ T cells in B cell-CXCR5+ CD4+ T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5+ CD8+ T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5+ CD8+ T cells tended to associate with low HBV DNA load, and the frequency of CXCR5+ CD8+ T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5+ CD8+ T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.

Bioactivity of CD34+ cells in patients with acute-on-chronic liver failure.

Liver failure is a life-threatened serious disease with many complications and high mortality rate. Stem cells have been applied to replacement therapy, gene therapy and tissue engineering for its capacity of self-renewal and multi-lineage differentiation. To investigate the bioactivity of the peripheral blood hematopoietic stem cells (PBHSC) in patients with acute-on-chronic liver failure, we isolated CD34+ cells from peripheral blood of patients with acute-on-chronic liver failure and healthy controls. After cultured it in serum-free medium (SFEM), we studied the bioactivity of CD34+ cells by observing the morphology, recording growth curve, detecting cell cycle and cell apoptosis. CD34+ cells and culture solution were collected at the time points of 3, 5, 7, 10, 12 and 14 days, and the levels of hepatocyte growth factor (HGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in culture solution were detected by ELISA. Also, the expressions of pyruvate kinase muscle isoenzyme 2 (PKM2), integrin-ß1 and liver-type pyruvate kinase (LPK) were detected by RT-PCR and immunofluorescence. Our results showed the bioactivity of CD34+ cells from patients with acute-on-chronic liver failure was identified to be similar with that from healthy controls. HGF, MMP-9, TNF-α and IL-6 were found in cell culture medium. RT-PCR and immunofluorescence results indicated that PKM2, Integrin-ß1 expressed on CD34+ cells from patients with acute-on-chronic liver failure. In conclusion, bioactivity of CD34+ cells of patients with acute-on-chronic liver failure was demonstrated to be normal, which could secrete HGF, MMP-9, TNF-α and IL-6, promote the growth of hepatocytes, and differentiate along a direction to hepatocyte lineage.

[The characterization of regulatory T cells in peripheral blood of HBV-infected patients].

OBJECTIVE: CD4(+)CD25(high) regulatory T cells (Treg) have been shown to play an important role in maintaining peripheral tolerance against self and foreign antigens, and in suppressing T cell immune response. Our aim was to characterize circulating Treg in HBV-infected patients. METHODS: Treg in peripheral blood from 72 chronic hepatitis B (CHB) patients, 16 acute hepatitis B (AHB) patients and 32 healthy subjects were quantitatively analyzed using flow cytometry. Serum HBV markers were evaluated for each subject. HBV-DNA levels were measured using real-time RT-PCR. RESULTS: CHB patients presented a higher fraction of circulating Treg (3.9% +/- 1.4%) than those in AHB patients (3.1% +/- 0.9%) (P < 0.05), but were similar to healthy controls (3.5% +/- 0.7%). CHB patients with greater than 10(7) copies/ml of serum HBV DNA loads had a higher frequency (4.5% +/- 1.9%) of circulating Treg than health controls (P < 0.01) and the patients with less than 10(7) copies/ml of serum viral loads (3.4% +/- 0.7%). A correlation was found between circulating Treg and HBV DNA level (r = 0.32, P < 0.01). Furthermore, Treg was more frequent in convalescent phase (6.0% +/- 1.7%) than in early acute phase (3.0% +/- 0.6%). CONCLUSION: Increased peripheral Treg is found to be associated with HBV replication in chronic hepatitis B. In acute HBV infection, Treg is less frequent in early phase. The related mechanisms is under further investigation.

Epidemiologic characteristics, clinical manifestations, and risk factors of 139 patients with Ebola virus disease in western Sierra Leone.

OBJECTIVE: We aimed to fully describe epidemiologic characteristics, clinical manifestations, and clinical outcomes of Ebola virus disease (EVD), as well as detect independent factors significantly associated with mortality of the disease. METHODS: One hundred thirty-nine confirmed EVD patients enrolled at the JUI Holding and Treatment Centre in western Sierra Leone between November 15, 2014, and January 18, 2015, and demographic and clinical data were retrospectively collected and analyzed. RESULTS: The median age of investigated patients was 29 years and 55.4% were women. Of them, 76 patients (54.7%) died and 63 patients (45.3%) were cured. Case fatality rate among male patients was higher than in female patients (69.4% vs 42.9%). Fatigue (82.0%), anorexia (70.5%), abdominal pain (59.7%), diarrhea (58.3%), vomiting (56.1%), fever (55.4%), and muscle pain (54.0%) were the most common symptoms. In addition, 55.4% of investigated patients reported fever. Bleeding was seen in 10.8% of patients. CONCLUSIONS: Our data show that mortality of EVD is associated with an older age, fever, and probably hiccups.

Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients.

BACKGROUND: A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease. METHODS: A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time. RESULTS: Among the 288 confirmed EVD patients (149 male and 139 female, median age 28 years, and median log viral load 6.68), 98 died, 36 recovered, and 154 were lost to follow-up. Common symptoms were fever (77.78%), fatigue (64.93%), abdominal pain (64.58%), headache (62.85%), and diarrhea (61.81%). Compared to patients aged<18 years, those who were older than 40 years had a higher probability of death (odds ratio 2.855, p=0.044). Patients with a viral load of >10(6) copies/ml had a higher case fatality rate than those with <10(6) copies/ml (odds ratio 3.095, p=0.004). Cox regression showed that age, viral load, and the presence of diarrhea correlated with mortality. CONCLUSION: Patients with a high viral load, of older age, and with diarrhea had a higher mortality and shorter survival time.

A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure

The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.