Epigenetically-regulated serum GAS5 as a potential biomarker for patients with chronic hepatitis B virus infection

2021 ◽  
pp. 1-10
Author(s):  
Yong Guo ◽  
Chunxue Li ◽  
Rongrong Zhang ◽  
Yating Zhan ◽  
Jinglu Yu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Promoter Methylation ◽  
Transforming Growth Factor ◽  
Free Form ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Chronic Hepatitis B Virus

BACKGROUND: Long non-coding RNA-growth arrest specific transcript 5 (lncRNA-GAS5) plays a suppressive role in activated hepatic stellate cells (HSCs). LncRNAs could circulate in the blood in a cell-free form and serve as promising biomarkers for various human diseases. Herein, we investigated the feasibility of using serum GAS5 as a biomarker for liver fibrosis in chronic hepatitis B (CHB) patients and whether promoter methylation was responsible for GAS5 down-regulation. METHODS: Serum GAS5 levels were quantified using quantitative real-time PCR in CHB patients and healthy controls. GAS5 promoter methylation was examined in LX-2 cells and cirrhotic tissues. RESULTS: Compared with the sera from healthy controls, lower GAS5 levels were found in the sera from CHB patients. Receiver operating characteristic curve analysis indicated that serum GAS5 had a significant diagnostic value for liver fibrosis in CHB patients. Serum GAS5 negatively correlated with HAI scores as well as ALT values in CHB patients. GAS5 was additionally reduced in cirrhotic tissues, associated with its hypermethylation promoter. In LX-2 cells, transforming growth factor-β1 treatment led to a reduction in GAS5 expression and an increase in promoter methylation. Hypermethylation of GAS5 was blocked down by DNA methyltransferase (DNMT) inhibitor and restored GAS5 inhibited HSC activation including proliferation and collagen production. Further studies confirmed that GAS5 methylation was mediated by DNMT1. CONCLUSION: We demonstrate that epigenetically-regulated serum GAS5 could serve as a potential biomarker in CHB patients. Loss of GAS5 is associated with DNMT1-mediated promoter methylation.

scholarly journals Serum Immunoglobulin A (IgA) Level Is a Potential Biomarker Indicating Cirrhosis during Chronic Hepatitis B Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Sha Lin ◽  
QinQin Sun ◽  
WeiLin Mao ◽  
Yu Chen
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Serum Immunoglobulin ◽  
Decompensated Cirrhosis ◽  
Healthy Controls ◽  
Serum Iga ◽  
Potential Biomarker ◽  
Chronic Hepatitis B Virus ◽  
Immunoglobulin Levels

Background. Serum immunoglobulins (Igs) are frequently elevated in patients with chronic liver disease, but currently there is a lack of sufficient data on serum Igs in patients with chronic hepatitis B virus (CHB) infection. This study aimed to evaluate serum IgA, IgG, and IgM levels in patients with HBV-related cirrhosis and to analyze, if altered, immunoglobulin levels that were associated with cirrhosis progress.Methods. A cohort of 174 CHB patients including 104 with cirrhosis (32 decompensated and 72 compensated) and 70 without cirrhosis and 55 healthy controls were enrolled. Serum immunoglobulin levels and biochemical and virological parameters were determined in the enrollment blood samples.Results. Serum IgA levels were significantly increased in cirrhosis group compared with noncirrhosis group and healthy controls (allP<0.001). Furthermore, serum IgA concentrations in decompensated cirrhosis patients were significantly higher than that of compensated patients (P=0.002). Multivariate analysis suggested that serum IgA, platelets, and albumin were independent predictors for cirrhosis (allP<0.001).Conclusions. Elevated IgA levels may function as an independent factor indicating cirrhosis, and there appears to be a strong association between increasing serum IgA level and disease progressing in patients with chronic HBV infection.

Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection

2017 ◽  
Vol 48 (4) ◽  
pp. 275-285 ◽  
Author(s):  
Satoru Joshita ◽  
Yuki Ichikawa ◽  
Takeji Umemura ◽  
Yoko Usami ◽  
Ayumi Sugiura ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Liver Fibrosis ◽  
Virus Infection ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Virus Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Fibrosis Marker

scholarly journals Spatial and functional links between cellular virological state and progression of liver fibrosis in chronic hepatitis B

2020 ◽  
Author(s):  
Xiaonan Zhang ◽  
Danping Liu ◽  
Wei Lu ◽  
Ye Zheng ◽  
Min Wu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Specific Antigen ◽  
Cellular Level ◽  
Hbv Infection ◽  
Dependent Manner ◽  
Chronic Hepatitis B Virus

AbstractChronic Hepatitis B Virus (HBV) infection is strongly associated with the progression of liver fibrosis, cirrhosis and hepatocellular carcinoma. Despite intensive study, the detailed mechanisms leading to HBV induced liver disease have not been fully elucidated. Previously, we reported a mosaic distribution of viral antigens and nucleic acids at single-cell level in liver tissues of chronic hepatitis B (CHB) patients and proposed a ‘three-stage model’ of HBV infection in vivo. Here, we explored whether the different stages at cellular level is functionally linked with fibrogenesis. We observed a tight spatial relationship between the invasion of collagen fibers and transitions from S-rich to DNA-rich stage. While S-rich cells mainly localized within minimally fibrotic tissue, DNA-rich cells were often closely surrounded by a milieu of stiffened extracellular matrix (ECM). cDNA microarray and subsequent validation analyses revealed that S-rich cells manifested elevated ribosomal proteins and oxidative phosphorylation genes in a disease phase-dependent manner. On the other hand, DNA-rich cells exhibited gradually deteriorated expression of hepatocyte-specific antigen and transcriptional regulator in parallel with the progression of hepatic fibrosis. Finally, during fibrogenesis, inflammatory genes such as IP-10 were found to be expressed in both portal infiltrated cells and surrounding parenchymal cells which resulted in suppressed antigen expression. Taken together, we propose that liver inflammation and accompanying fibrogenesis is spatially and functionally linked with the transition of virological stages at cellular level. These transitions occur possibly due to an altered hepatocyte transcription profile in response to a transformed ECM environment. The collective viral and host activities shape the histological alterations and progression of liver disease during CHB infection.

Adipocytokines and liver fibrosis stages in patients with chronic hepatitis B virus infection

2015 ◽  
Vol 9 (2) ◽  
pp. 231-242 ◽  
Author(s):  
Ching-Sheng Hsu ◽  
Wei-Liang Liu ◽  
You-Chen Chao ◽  
Hans Hsienhong Lin ◽  
Tai-Chung Tseng ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Liver Fibrosis ◽  
Virus Infection ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Virus Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Noninvasive Markers of Liver Fibrosis and Inflammation in Chronic Hepatitis B-Virus Related Liver Disease

2006 ◽  
Vol 101 (11) ◽  
pp. 2537-2545 ◽  
Author(s):  
Mehdi Mohamadnejad ◽  
Ghodrat Montazeri ◽  
Atoosa Fazlollahi ◽  
Farhad Zamani ◽  
Jafar Nasiri ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis B Virus ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Noninvasive Markers ◽  
Related Liver Disease

scholarly journals Assessment of liver fibrosis by transient elastography in young children with chronic hepatitis B virus infection

2021 ◽  
Author(s):  
Zhiqiang Xu ◽  
Jinfang Zhao ◽  
Jiaye Liu ◽  
Yi Dong ◽  
Fuchuan Wang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Fibrosis Stage ◽  
Advanced Fibrosis ◽  
Specificity And Sensitivity ◽  
Chronic Hepatitis B Virus

Abstract Background This study aimed to compare the diagnostic accuracy of transient elastography (TE) and biopsy for the detection of liver fibrosis in children with chronic hepatitis B (CHB). Methods This single-center prospective study included 157 CHB children aged 0–6 years. All patients underwent liver stiffness measurement (LSM) by TE and liver biopsy, separated by an interval of less than 1 week. Results The LSM, aspartate aminotransferase-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) were positively correlated with activity grade and fibrosis stage in CHB children. The areas under the receiver operating characteristic curves (AUCs) of LSM for identifying significant (F ≥ 2) and advanced (F ≥ 3) fibrosis were 0.732 and 0.941, respectively. The cut-off values, specificity, and sensitivity for significant fibrosis were 5.6 kPa, 75.7%, and 67.4%, respectively; the corresponding values for advanced fibrosis were 6.9 kPa, 91.5%, and 81.3%, respectively. Compared to LSM, the overall diagnostic performances of APRI and FIB-4 for significant and advanced fibrosis were suboptimal, with low AUCs and sensitivity. Since LSM, platelet, and Log10 (hepatitis B surface antigen) were independent factors associated with the fibrosis stage (F < 2 and F ≥ 2), they were used to formulate the “LPS” index for the prediction of F ≥ 2. The AUC of LPS (for F ≥ 2) was higher than that of LSM (0.792 vs. 0.732, p < 0.05), and had an improved sensitivity (76.6% vs. 67.4%). Conclusions TE is a promising technology for the diagnosis of advanced fibrosis in CHB children aged 0–6 years.

scholarly journals Cytokines and Chemokines in HBV Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Shihong Zhong ◽  
Tianling Zhang ◽  
Libo Tang ◽  
Yongyin Li
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Hbv Infection ◽  
Cytokines And Chemokines ◽  
Immune Exhaustion ◽  
Chronic Hepatitis B Virus

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

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