Serum EV proteome non-target analysis of liver fibrosis in chronic hepatitis C patients
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ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Tetsuo Takehara
PROVIDER: PXD031283 | JPOST Repository | Thu Jan 26 00:00:00 GMT 2023
REPOSITORIES: jPOST
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Project description:Serum EV proteome target analysis of liver fibrosis in chronic hepatitis C patients was performed.
2023-01-27 | PXD031289 | JPOST Repository
Project description:Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients
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Project description:Background & Aims: Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection. Methods: Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B. Results: There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., IFIT2, IFI27, IFITM1, IFI6), and macrophage gene signatures (e.g., MARCO, CD163, CD5L, CD63), when compared to patients with ENEG alone. Conclusions: Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.
2024-10-31 | GSE274114 | GEO
Project description:Molecular characterization of chronic liver disease dynamics: from liver fibrosis to acute-on-chronic liver failure
| PRJNA580468 | ENA
Project description:Metabolomics offers new insights into disease mechanisms that is enhanced when adopting orthogonal instrumental platforms to expand metabolome coverage, while also reducing false discoveries by independent replication. Herein, we report the first inter-method comparison when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) and nuclear magnetic resonance (NMR) spectroscopy for characterizing the serum metabolome of patients with liver fibrosis in chronic hepatitis C virus (HCV) infection (<i>n</i> = 20) and non-HCV controls (<i>n</i> = 14). In this study, 60 and 30 serum metabolites were detected frequently (>75%) with good technical precision (median CV < 10%) from serum filtrate samples (<i>n</i> = 34) when using standardized protocols for MSI-CE-MS and NMR, respectively. Also, 20 serum metabolite concentrations were consistently measured by both methods over a 500-fold concentration range with an overall mean bias of 9.5% (<i>n</i> = 660). Multivariate and univariate statistical analyses independently confirmed that serum choline and histidine were consistently elevated (<i>p</i> < 0.05) in HCV patients with late-stage (F2-F4) as compared to early-stage (F0-F1) liver fibrosis. Overall, the ratio of serum choline to uric acid provided optimal differentiation of liver disease severity (<i>AUC</i> = 0.848, <i>p</i> = 0.00766) using a receiver operating characteristic curve, which was positively correlated with liver stiffness measurements by ultrasound imaging (<i>r</i> = 0.606, <i>p</i> = 0.0047). Moreover, serum 5-oxo-proline concentrations were higher in HCV patients as compared to non-HCV controls (<i>F</i> = 4.29, <i>p</i> = 0.0240) after adjustment for covariates (age, sex, BMI), indicative of elevated oxidative stress from glutathione depletion with the onset and progression of liver fibrosis. Both instrumental techniques enable rapid yet reliable quantification of serum metabolites in large-scale metabolomic studies with good overlap for biomarker replication. Advantages of MSI-CE-MS include greater metabolome coverage, lower operating costs, and smaller sample volume requirements, whereas NMR offers a robust platform supported by automated spectral and data processing software.
2023-08-22 | MTBLS3111 | MetaboLights
Project description:We sought to clarify the correlation between non-protein respiratory quotient (npRQ) in indirect calorimetry and serum zinc (Zn) level in chronic liver diseases (CLDs, n = 586, 309 liver cirrhosis (LC) patients, median age = 63 years). Clinical parameters potentially linked to npRQ <0.85 (best cutoff point for the prognosis in LC patients) were also examined in receiver operating characteristic curve (ROC) analyses. The median npRQ was 0.86. The median serum Zn level was 64 ?g/dL. The median npRQ in patients with non-LC, Child-Pugh A, Child-Pugh B and Child-Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p < 0.0001)). The median serum Zn level in patients with npRQ <0.85 (58 ?g/dL) was significantly lower than that in patients with npRQ ? 0.85 (68 ?g/dL) (p < 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p < 0.0001). Similar tendencies were observed in all subgroup analyses. The highest correlation coefficient between serum Zn level and npRQ was found in patients with Child-Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ <0.85, serum Zn level had the highest area under the ROC (AUC) among baseline laboratory parameters (AUC = 0.69). In conclusion, serum Zn level can be helpful for npRQ in patients with CLDs.
| S-EPMC7019764 | biostudies-literature
Project description:In the research field of extracellular vesicles (EVs), the use of EV-depleted fetal bovine serum (FBS) for in vitro studies is highly recommended to eliminate the confounding effects of media derived EVs. EV-depleted FBS may either be prepared by ultracentrifugation or bought commercially, nevertheless these depletion methods do not guarantee an RNA-free preparation. In this study we have addressed the RNA contamination issue in FBS, ultracentrifuged EV-depleted FBS, commercially available EV-depleted FBS, and also from our recently developed filtration based EV depleted FBS. Commercially available serum-free, xeno-free defined media were also screened for RNA contamination.
2019-04-30 | GSE120594 | GEO
Project description:Background and aims: We aimed to study the pathogenesis of AH in an animal model of acute-on-chronic alcoholic liver disease which combines chronic hepatic fibrosis with intragastric alcohol administration. Methods: Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (EtOH) (up to 25 g/kg/day, for 3 weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4. Liver and serum markers were evaluated to characterize acute-on-chronic-alcoholic liver disease in our model. Results: CCl4 or EtOH treatment alone induced liver fibrosis or steatohepatitis, respectively, findings that were consistent with expected pathology. Combined treatment with CCl4 and EtOH resulted in a marked exacerbation of liver injury, as evident by the development of hepatic inflammation, marked steatosis, and pericellular fibrosis, and by increased serum transaminase levels, compared to mice treated with either treatment alone. Liver transcriptomic changes specific to combined treatment group demonstrated close concordance with pathways perturbed in human severe cases of AH. In addition to gene expression changes, E. coli and Candida species were also significantly more abundant in livers of mice co-treated with CCl4 and EtOH. Conclusions: Mice treated with CCl4 and EtOH displayed several key characteristics of human AH, including pericellular fibrosis, increased hepatic bacterial load, and dysregulation of the same molecular pathways. This model may be useful for developing therapeutics for AH.
2018-09-05 | GSE119470 | GEO
Project description:Purpose: Chronic Hepatitis B virus (HBV) infection leads to liver fibrosis which is a major risk factor in Hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. HBV genome can be inserted into human genome, and chronic inflammation may trigger somatic mutations. Several studies characterized HBV integration sites in HCC patients with regard to frequently occurring hotspots. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regard to different degree of liver fibrosis is not clearly understood. In this study, we aim to find potential molecular mechanisms underlying tumor recurrence of HBV-associated HCC (HBV-HCC) with different degree of liver fibrosis. Methods: We performed RNA sequencing of 21 pairs of tumor and non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analysis of our RNAseq data and public available sequencing data related to HBV-HCC. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations with sequencing data showed that our method outperformed existing methods. We also compared SNPs of each sample with SNPs in cancer census database and inferred patient’s pathogenic SNP loads in tumor and non-neoplastic liver tissues. Conclusions: The HBV-integration and pathogenic SNP load patterns for HCC recurrence risk vary depending on liver fibrosis stage, suggesting potentially different tumorigenesis mechanisms for low and high liver fibrosis patients.
2018-03-01 | GSE94660 | GEO
Project description:Background/Aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.
2021-07-15 | GSE179961 | GEO