Chronic Hepatitis
Chronic Hepatitis is the long-term inflammation of the liver that can result in progressive liver damage/threatening scarring (cirrhosis) as well as cancer (hepatocellular carcinoma) down the line. Protheragen's MyD88-targeted therapy seeks to resolve the modulation of inflammation, scarring (fibrosis), and chronic liver damage appearing in chronic liver disease outcomes.
Introduction to Chronic Hepatitis
Chronic Hepatitis is defined by inflammation and liver cell damage lasting for at least 6 months. More frequent reasons include chronic viral infections (HBV, HCV), metabolic syndrome-associated fatty liver disease (NASH), alcohol abuse, and autoimmune liver disease. This condition ranges from inflammation being the primary finding to severe fibrosis and cirrhosis. Even though many different initiating triggers exist, chronic inflammation is a consistent factor leading to liver damage.
Pathogenesis of Chronic Hepatitis
- Chronic Inflammation and Innate Immune Dysregulation
Hepatitis develops from ongoing activation of the immune cells in the liver, including Kupffer cells, which in turn activate TLR/MyD88 pathways that detect PAMPs/DAMPs (detection of pathogens or tissue injury). This leads to inflammation in the liver which sustains itself due to the release of cytokines (TNF-α, IL-1β) and chemokines that mobilize immune cells and continue the cycle of damage to liver cells.
- Hepatocyte Death and Fibrotic Progression
Persistent inflammation along with direct damage to hepatocytes promotes cell death which DAMP amplifies MyD88-dependent pathways. At the same time, the activated hepatic stellate cells (HSCs) undergo transformation into collagen-secreting myofibroblasts mediating MyD88-associated cross talk between immune cells and HSCs, resulting in permanent fibrosis and severe liver damage.
Fig.1 Graphic representation of anti-viral cytokine production and regulation of apoptosis in trophoblasts during HBV infection. (Zhao, Bai and Xi, 2022)MyD88-Targeted Therapeutic Development for Chronic Hepatitis
Any approaches designed at targeting MyD88-dependent signaling pathway have a good chance of success. This is because the pathway can be targeted to disrupt the chronic inflammation and subsequent fibrosis progression in Chronic Hepatitis, regardless of primary cause. These proposed therapies decrease the activation fibrogenic cells and pro-inflammatory cytokines by targeting this central node.
| Therapeutic Strategy | Mechanism of Action | Representative Approaches | Development Stage |
| TLR4/MyD88 Signaling Inhibition | Block MyD88-dependent TLR4 signaling to reduce proinflammatory cytokines (IL-6, TNF-α) and fibrosis. | TLR4 antagonists (e.g., TAK-242), MyD88 dimerization inhibitors (e.g., ST2825). | Preclinical |
| Fecal Microbiota Transplantation (FMT) | Restore gut-liver axis balance via TLR4/11-MyD88 pathway to correct TFR/TFH cell imbalance. | Therapeutic FMT in autoimmune hepatitis (AIH) models. | Preclinical |
| CXCR3 Knockdown | Suppress TLR4/MyD88 signaling to inhibit fibrosis and cancer progression in HBV-related cirrhosis. | CXCR3 siRNA or small-molecule inhibitors (e.g., AMG487). | Preclinical |
| miR-146a Modulation | Downregulate TLR2-MyD88-driven miR-146a overexpression in HCV-infected monocytes. | Anti-miR-146a oligonucleotides or TLR2 antagonists (e.g., OPN-305). | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides MyD88-targeted therapeutic discovery and advanced disease models development services specifically tailored for chronic hepatitis. Our multi-dimensional disease models facilitate the screening and evaluation of MyD88 signaling modulators to accelerate preclinical intervention development.
Therapeutic Discovery Platform for Chronic Hepatitis
Protheragen offers an integrated platform for MyD88-targeted Chronic Hepatitis therapeutic discovery that simultaneously addresses chronic inflammation, fibrosis, and liver damage. The focus is on modulating or by passing MyD88 signaling loops through specific pathway-driven disease models designed for preclinical investigation, targeting the unrestrained innate immunity activation and its contribution to liver pathology.
Disease Models Development for Chronic Hepatitis
Protheragen offers extensive in vitro & in vivo models for chronic hepatitis including cell-based models, organoid models, and animal models, enabling the comprehensive evaluation of MyD88-targeted therapeutic strategies. These models provide critical insights into therapeutic efficacy against the core pathophysiological processes of chronic liver disease.
- Activated Hepatic Stellate Cell Culture
- Primary Hepatocyte/Kupffer Cell Co-culture Systems
- Liver Organoid Models
- CCl4-Induced Fibrosis Models
- Thioacetamide (TAA)-Induced Fibrosis Models
- Diet-Induced NASH/Fibrosis Models
- Viral Hepatitis Models
Protheragen advances MyD88-targeted drug discovery for chronic liver diseases through end-to-end solutions, including disease model development, pharmacokinetics and drug safety evaluation, and investigator-initiated trials, to de-risk and expedite therapeutic development.
If you are interested in our services, please don't hesitate to contact us.
References
- Yuan, G., et al. "Role of the Cxcr3‑Mediated Tlrs/Myd88 Signaling Pathway in Promoting the Development of Hepatitis B into Cirrhosis and Liver Cancer." Mol Med Rep 24.4 (2021).
- Zhao, X., X. Bai, and Y. Xi. "Intrauterine Infection and Mother-to-Child Transmission of Hepatitis B Virus: Route and Molecular Mechanism." Infect Drug Resist 15 (2022): 1743-51.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.