Project description:Hepatitis B virus (HBV)-associated acute on chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. To explore potential biomarkers of HBV-ACLF for clinical applications, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified and quantified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples (p<0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.
Project description:The varying individual responses to Peg-IFNα in patients with CHB pose significant hurdles in treatment optimization, and the underlying mechanisms remain unclear. We aimed to identify genetic polymorphisms influencing the efficacy of Peg-IFNα in patients with HBeAg-positive CHB,with the goal to predict Peg-IFNα response before treatment.
Project description:To further identify the fecal miRNAs generated in HE, we conducted an miRNA microarray analysis on feces collected from patients with HE and CHB. The microarray analysis of miRNA expression profiles revealed that the abundance of 10 miRNAs was significantly increased in feces from patients with HE, as compared with that from patients with CHB, whereas the abundance of 8 miRNAs was decreased.
Project description:The low frequency of HBV-specific CD8+ T cells in the peripheral blood of CHB patients has limited studies of the mechanisms underlying HBV-induced T cell exhaustion. Similar to the expansion defect displayed in HBV-specific CD8+ T cells, TCR-induced proliferation of global CD8+ T cells is impaired in a fraction of chronic HBV (CHB) patients. Thus, examining the molecular regulation of global CD8+ T cell function in CHB patients may provide insight into the exhaustion of HBV-specific CD8+ T cells. We used microarrays to detail the global programme of gene expression of CD8 T cells from CHB patients who have not received anti-viral treatment. Fifteen milliliters of blood was drawn from eachof three CHB patients and three healthy donors. PBMCs were enriched using Ficoll, and CD8+ T cells were purified using positive selection beads to a purity of >95% (Miltenyi Biotec, Auburn, CA). Total RNA was extracted using a mirVana isolation kit (Life Technologies, Carlsbad, CA).
Project description:The low frequency of HBV-specific CD8+ T cells in the peripheral blood of CHB patients has limited studies of the mechanisms underlying HBV-induced T cell exhaustion. Similar to the expansion defect displayed in HBV-specific CD8+ T cells, TCR-induced proliferation of global CD8+ T cells is impaired in a fraction of chronic HBV (CHB) patients. Thus, examining the molecular regulation of global CD8+ T cell function in CHB patients may provide insight into the exhaustion of HBV-specific CD8+ T cells. We used microarrays to detail the global programme of gene expression of CD8 T cells from CHB patients who have not received anti-viral treatment.
Project description:There were 3 patients with CHB and 3 patients with SC HBV in microarray analysis. As for the liver function parameters, the average HBsAg and HBeAg levels of CHB group were obviously higher than SC HBV group. The obtained RNAs expression profiles were analyzed by microarray analysis. A total of 513 lncRNAs, 256 mRNAs and 48 miRNAs were found to be differentially expressed (DE) in patients with CHB compared with patients with SC HBV (fold change > 1.2 and P < 0.05).
Project description:Background: Chronic hepatitis B (CHB) infection is a serious health problem worldwide and with the current treatment a functional cure is only achieved in 3-15% of the patients. Therefore it is important to investigate novel biomarkers for treatment outcome and to develop new treatment options for CHB. miRNAs are small, non-coding RNA molecules that are involved in various cellular processes by regulating gene expression at the posttranscriptional level and also play an important role in a variety of infectious diseases. In this study we want to identify novel miRNAs that are involved in hepatitis B replication and could therefore be used as biomarkers and targeted as a potential new therapeutic option. Methods: miRNA/small RNA NGS was performed on total RNA isolated from 10 matching plasma and liver biopsy of an identification cohort of CHB patients and 10 plasma and liver controls. Results: We identified 23 and 18 miRNAs that were differentially expressed between controls and CHB patients in plasma and liver respectively, of which five were differentially expressed in both liver and plasma. Of these candidate miRNAs 3 were upregulated in liver and 12 in plasma from CHB and 15 were downregulated in liver and 11 in plasma.
Project description:To identify serum miRNAs for the diagnosis of HCC, the profiling of 754 human miRNAs was analyzed in sera from six histopathologically confirmed HCC patients and eight CHB controls, using TaqMan Array Human MicroRNA A+B Cards Set v3.0 (Applied Biosystems, Foster City, CA). Serum miRNAs with differential levels between HCC and CHB were identified by comparing serum miRNA profiling of HCC patients with that of CHB controls.
2016-02-01 | GSE65708 | GEO
Project description:HBV preS sequencing of CHB patients
Project description:Rituximab (RTX) is widely used as a first-line therapeutic strategy for patients affected by immune thrombocytopenia (ITP). However, a large proportion of patients relapse after successful treatment. The present NGS assay was done to help find the cause for this relapse on the immune repertoire level. Therefore, we performed antibody repertoire sequencing for three RTX relapse patients with subsequent mutation and clonal analysis, as well as for two patients with ongoing ITP and two healthy donors (HD) with subsequent mutation analysis.