IFN-gamma inhibits hepatic progenitor cell activation in patients with chronic hepatitis B and in mice

Each phase of hepatitis B infection stimulates distinct viral kinetics and host immune responses resulting in liver damage and hepatic fibrosis. Our objective has been to correlate host inflammatory immune response including circulating Th1 and Th2 cytokines in patients with chronic hepatitis B infection with liver histopathology. Sixty-four patients with chronic hepatitis B without previous treatment were recruited. The liver histology and histological activity index were assessed for various degrees of necroinflammation and hepatic fibrosis. We determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and 18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64 (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma were significantly correlated with degrees of necroinflammation (r=0.34, r=0.38, resp.; P<0.05). Moreover, TNF-alpha was significantly correlated with degrees of fibrosis (r=0.35; P<0.05), and IL-10 and TNF-alpha were significantly correlated with significant fibrosis (r=0.39, r=0.35, resp.; P<0.05). These correlations were found in the HBeAg negative group as opposed to the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10 and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10 and TNF-alpha were correlated with significant fibrosis.

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Peroxisome proliferator-activated receptor γ inhibits hepatic stellate cell activation regulated by miR-942 in chronic hepatitis B liver fibrosis

Life Sciences ◽

10.1016/j.lfs.2020.117572 ◽

2020 ◽

Vol 253 ◽

pp. 117572 ◽

Cited By ~ 1

Author(s):

Le Tao ◽

Liu Wu ◽

Wei Zhang ◽

Wen-ting Ma ◽

Guang-yue Yang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Hepatic Stellate Cell Activation

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Novel Antivirals in Clinical Development for Chronic Hepatitis B Infection

Viruses ◽

10.3390/v13061169 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1169

Author(s):

Lung-Yi Mak ◽

Wai-Kay Seto ◽

Man-Fung Yuen

Keyword(s):

Chronic Hepatitis ◽

T Cell ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

T Cell Activation ◽

Viral Entry ◽

Cell Activation ◽

Core Protein ◽

Safety Data ◽

Decompensated Cirrhosis

Globally, chronic hepatitis B (CHB) infection is one of the leading causes of liver failure, decompensated cirrhosis, and hepatocellular carcinoma. Existing antiviral therapy can suppress viral replication but not fully eradicate the virus nor the risk of liver-related complications. Novel treatments targeting alternative steps of the viral cycle or to intensify/restore the host’s immunity are being developed. We discuss novel drugs that have already entered clinical phases of development. Agents that interfere with specific steps of HBV replication include RNA interference, core protein allosteric modulation, and inhibition of viral entry or viral protein excretion (NAPs and STOPS). Agents that target the host’s immunity include toll-like receptor agonists, therapeutic vaccines, immune checkpoint modulators, soluble T-cell receptors, and monoclonal antibodies. Most have demonstrated favorable results in suppression of viral proteins and genomic materials (i.e., HBV DNA and/or pre-genomic RNA), and/or evidence on host-immunity restoration including cytokine responses and T-cell activation. Given the abundant clinical experience and real-world safety data with the currently existing therapy, any novel agent for CHB should be accompanied by convincing safety data. Combination therapy of nucleos(t)ide analogue, a novel virus-directing agent, and/or an immunomodulatory agent will be the likely approach to optimize the chance of a functional cure in CHB.

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Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment

Scientific Reports ◽

10.1038/s41598-021-86836-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sriram Narayanan ◽

Veonice Bijin Au ◽

Atefeh Khakpoor ◽

Cheng Yan ◽

Patricia J. Ahl ◽

...

Keyword(s):

Chronic Hepatitis ◽

T Cell ◽

Network Analysis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

T Cell Activation ◽

Cell Activation ◽

Hbsag Loss ◽

Immune Pathways

AbstractOur objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.

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