IL-21 Is Associated With Virological Relapse of HBeAg Positive Chronic Hepatitis B After Discontinuance of Entecavir

Huang, Lihua; Zhou, Licheng; Gan, Jing; Yang, Wenlong; Dai, Yaping; Su, Tingting; Qiu, Yuanwang

doi:10.5152/tjg.2021.19703

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…Serum levels of IL-21 at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment in CHB patients with telbivudine treatment or salvage therapy ( Ma et al, 2012 ; Li et al, 2021b ). Additionally, serum IL-21 levels at 0, 12, 24, 52, and 104 weeks after discontinuance of entecavir are significantly higher in the durable virological remission group than in the virological relapse group ( Huang et al, 2021 ).…”

Section: Cytokines In Hepatitis B Virus Infectionmentioning

confidence: 98%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

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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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Section: Cytokines In Hepatitis B Virus Infectionmentioning

confidence: 98%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

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“…This large prospective RCT, consisting mostly of Asian participants, strengthens the notion that stopping NA therapy, especially before HBsAg loss, is not beneficial but poses a risk of complications and retreatment, which is an unfavorable outcome. Contrary to another study, done predominantly in white people, shows that discontinuation of NA in HBeAg-negative patients will lead to a functional cure, i.e., HBsAg loss [18]. Out of 69 patients, only one developed HCC, as he had cirrhosis at baseline.…”

Section: Discussionmentioning

confidence: 66%

“…Our PRISMA flow diagram is shown below in Figure 1. Baseline characteristics: These characteristics and definitions are generalized to all reviewed articles [16][17][18][19][20][21][22].…”

Section: Literature Search and Study Selectionmentioning

confidence: 99%

A Systematic Review on Current Trends in the Treatment of Chronic Hepatitis B to Predict Disease Remission and Relapse

Butt¹,

Satnarine²,

Ratna³

et al. 2022

Cureus

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Despite decreasing the prevalence of chronic hepatitis B (CHB), it is still a major health care challenge. Current antiviral regimens aim to suppress hepatitis B virus (HBV) deoxyribonucleic acid (DNA) activity to prevent the risk of hepatic decompensation, liver cirrhosis, and hepatocellular carcinoma (HCC). Currently, pegylated interferon (Peg-IFN) and nucleos(t)ide analogs (NA) are the first-line choices of drugs. Peg-IFN is now discontinued due to its mode of application and side effects. NA is used once daily to suppress HBV DNA activity but has little effect on covalently closed circular DNA (cccDNA), so continuous long-term therapy is required to suppress HBV DNA. Due to this effect, disease remission, relapse, and even clinical flare are common phenomena after the end of treatment (EOT). This review aimed to analyze the current regimens for treating chronic hepatitis B. Their mode of action, duration of treatment, and events after stopping therapy. The review was performed using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020 guidelines. A search was undertaken in PubMed, PubMed Central, Google Scholar, and ScienceDirect. Screening of articles was carried out to find relevant and appropriate articles. Articles were then quality-checked before inclusion.Our analysis showed that long-term finite therapy with nucleoside analogs could improve clinical outcomes and suppress viral DNA activity. However, a functional cure, loss of hepatitis B surface antigen (HBsAg), is rarely achieved. The decision to end treatment depends on quantitative HBsAg level (qHBsAg), alanine aminotransferase (ALT), HBV DNA (deoxyribonucleic acid), hepatitis B e antigen (HBeAg), and fibrosis assessment. It is concluded that patients with HBeAg negative without cirrhosis can be easily withdrawn from treatment if they have long-term viral remission and a high HBsAg loss rate. However, patients with positive HBeAg should continue treatment because there is a high chance of disease relapse and even acute flare. To predict whether patients will benefit from EOT, some immunomodulatory markers are studied, including interleukin (IL-20, IL-8), fas ligand (FASGL), and IFN gamma. Although these factors are reliable, none pose an independent effect on disease remission. Combination therapy (IFN alpha + oral nucleoside analogs) is promising but has clinical shortcomings.

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“…This is in line with many studies demonstrating that IL-37 is correlated with ALT, AST, and OPG in chronic HBV subjects. (33,34) This could be attributed to inflammation caused by the host immune system's defenses against viral infections. ( 35) TLR ligands like TLR2 and TLR4 can stimulate the production of IL-37 during an infection.…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin and Interleukin-37 are Correlated with Liver Diseases in Chronic Hepatitis B Virus (HBV)-infected Subjects

Alsalimi,

Al-Mashkor,

Al-Fartosy

2023

Indones Biomed J

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BACKGROUND: Various biological markers have been proposed to predict subclinical events in subjects with chronic hepatitis B virus (HBV). However, studies regarding chronic HBV infection are still limited. The current study aimed to investigate the relationship between osteoprotegerin (OPG) and interleukin-37 (IL-37) serum levels in chronic HBV subjects.METHODS: Sixty subjects with chronic HBV infection without previous treatment and 30 healthy subjects were included in this study. Blood samples were withdrawn and examined for biochemical parameters through the use of enzyme-linked immunosorbent assay (ELISA) assessments. Moreover, anthropometric estimations and medical histories were performed on all subjects through a standard self-administered questionnaire.RESULTS: A highly significant elevation (p<0.01) in serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and IL-37 and a significant increase (p<0.05) in serum level of OPG were observed in chronic HBV subjects compared with the controls. The data demonstrated that OPG had a positive correlation with IL-37 and that both OPG and IL-37 had significantly positive correlations with ALT and AST. Furthermore, the area under the receiver operating characteristics (ROC) curve (AUC) was computed for ALT, AST, OPG, and IL-37 (AUC = 0.831, 0.829, 0.608, and 0.618, respectively) which could be potentially greater predictive biomarkers in chronic HBV subjects.CONCLUSION: The positive correlation of OPG and IL-37 with ALT and AST and the high positive value of AUC for OPG and IL-37 shows that OPG and IL-37 could to be potential inflammatory biomarkers for the early onset of liver disease and hepatocellular carcinoma in chronic HBV-infected subjects.KEYWORDS: osteoprotegerin, interleukin-37, hepatitis B virus, inflammation, liver

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IL-21 Is Associated With Virological Relapse of HBeAg Positive Chronic Hepatitis B After Discontinuance of Entecavir

Cited by 6 publications

References 27 publications

Cytokines and Chemokines in HBV Infection

Cytokines and Chemokines in HBV Infection

A Systematic Review on Current Trends in the Treatment of Chronic Hepatitis B to Predict Disease Remission and Relapse

Osteoprotegerin and Interleukin-37 are Correlated with Liver Diseases in Chronic Hepatitis B Virus (HBV)-infected Subjects

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