Development of prognostic biomarkers for HBV-related acute-on-chronic liver failure
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Lanjuan Li
PROVIDER: PXD017928 | iProX | Sat Mar 07 00:00:00 GMT 2020
REPOSITORIES: iProX
Publications
Plasminogen as a prognostic biomarker for HBV-related acute-on-chronic liver failure.
Wu Daxian D Zhang Sainan S Xie Zhongyang Z Chen Ermei E Rao Qunfang Q Liu Xiaoli X Huang Kaizhou K Yang Jing J Xiao Lanlan L Ji Feiyang F Jiang Zhengyi Z Zhao Yalei Y Ouyang Xiaoxi X Zhu Danhua D Dai Xiahong X Hou Zhouhua Z Liu Bingjie B Deng Binbin B Zhou Ning N Gao Hainv H Sun Zeyu Z Li Lanjuan L
The Journal of clinical investigation 20200401 4
BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prosp ...[more]
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Project description:Genome wide microRNA profiling in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients of in different prognoses of 28-day. The Agilent Human miRNA Microarray Kit was used to obtain RNA profiles in 8 survival patients and 8 dead patients in 28-day.
2021-05-19 | GSE168046 | GEO
Project description:Genome wide mRNA profiling in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients of in different prognoses of 28-day. The Agilent SurePrint G3 Human Gene Expression ver. 3 8x60K Microarray was used to obtain RNA profiles in 8 survival patients and 8 dead patients in 28-day.
2021-05-19 | GSE168048 | GEO
Project description:BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148).RESULTSPlasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P < 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P < 0.001) than that of patients with low plasminogen levels. During hospitalization, plasminogen levels significantly decreased (P = 0.008) in the deterioration group but significantly increased (P < 0.001) in the improvement group. Additionally, plasminogen levels gradually increased in survivors but gradually decreased in nonsurvivors. The P5 score, a prognostic panel incorporating plasminogen levels, hepatic encephalopathy occurrence, age, international normalized ratio (INR), and total bilirubin, was significantly superior to the Child-Pugh, Model for End-stage Liver Disease (MELD), Chronic Liver Failure Consortium ACLF (CLIF-C ACLF), Chinese Group on the Study of Severe Hepatitis B (COSSH), and HINT (a prognostic score based on hepatic encephalopathy occurrence, INR, neutrophil count, and thyroid-stimulating hormone) scores (all P < 0.05). The performances of the plasminogen level and P5 score were validated in a second multicenter, prospective cohort (n = 148).CONCLUSIONSPlasminogen is a promising prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF.FUNDINGThe National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).
| S-EPMC7108894 | biostudies-literature
Project description:Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.
| S-EPMC9477565 | biostudies-literature
Project description:Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. ALF was characterized by overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes. By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF. Liver samples were obtained from explanted livers of two patients with HBV-associated ALF (4 samples per liver), 8 normal liver donors and 11 patients who underwent resection for angioma. Gene expression profiling was used to establish a molecular definition of ALF. Patient data derived from associated publication Table S2. This dataset is part of the TransQST collection.
2010-04-26 | E-GEOD-14668 | biostudies-arrayexpress
Project description:Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases. Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF. Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group. Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis. Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis. Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).
| S-EPMC8455926 | biostudies-literature
Project description:Recent implication of microRNAs (miRNAs) in the intricate cross-talk between the host and the pathogen in viral infections reveals a new layer of mechanism for host-virus interactions. In the present study, we investigated human miRNAs which may be involved in the acute and chronic HBV infections via microarray profiling. We determined the global miRNA expression profiles elicited in the uninfected control model (HepG2), the acute infection model (HepG2 transfected with a 1.3 full-length HBV genome) and the chronic infection model (HepG2.2.15) using CapitalBio corporation’s mammalian miRNA arrays. Three cellular models were used in this study: the human hepatoblastoma cell line HepG2 as a blank control representing the condition without virus infection; HepG2 transfected with a 1.3 full-length HBV genome as an acute infection model; and HepG2.2.15, a well-established cell line derived from HepG2 transfected with a full-length HBV genome and constitutively expressing HBV, as a chronic infection model.
2010-06-16 | E-GEOD-22378 | biostudies-arrayexpress
Project description:The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion: Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer. Liver samples were obtained from explanted liver of four patients with HBV-associated acute liver failure (4-5 samples per liver) and 10 individual normal liver donors and gene expression profiling was used to establish a molecular definition of this disease. This dataset is part of the TransQST collection.
2012-12-01 | E-GEOD-38941 | biostudies-arrayexpress
Project description:Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. ALF was characterized by overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes. By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.
2010-04-26 | GSE14668 | GEO
Project description:Background and aimsAcute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients.MethodsQuantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro.ResultsCirculating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients' neutrophils.ConclusionsCirculating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.
| S-EPMC7947208 | biostudies-literature