The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection

Area of Science:

• Immunology
• Hepatology
• Oncology

Background:

• Chronic hepatitis B (CHB) impacts 400 million globally, leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC).
• Cellular immune regulation is critical in determining the outcome of hepatitis B virus (HBV) infection.
• Understanding co-signal molecules and T helper 17/regulatory T cell (Th17/Treg) dynamics is key to exploring HBV progression.

Purpose of the Study:

• To investigate the association between co-signal molecules, Th17/Treg balance, and the progression of HBV infection.
• To explore the roles of Stat3 and Stat5 in the context of CHB, LC, and HCC.

Main Methods:

• Flow cytometry was used to analyze co-signal molecules, Th17/Treg populations, and Stat3/Stat5 levels.
• Ninety-four patients with HBV infection were classified into three groups: CHB with LC, CHB with HCC, and CHB alone.

Main Results:

• Patients with CHB-induced LC or HCC exhibited significantly higher levels of co-inhibitory molecules, including BTLA and PD-1.
• No significant differences in co-stimulatory molecules were observed among the CHB, LC, and HCC groups.
• Stat3 and Stat5 levels were significantly elevated in patients with LC and HCC compared to those with CHB.

Conclusions:

• Co-inhibitory molecules (PD-1, BTLA/HVEM) play a more critical role than co-stimulatory molecules in HBV progression.
• Activated Stat3 and Stat5 contribute to imbalanced Th17/Treg differentiation, inducing immune tolerance and HBV persistence.
• This immune dysregulation promotes hepatic inflammation, ultimately leading to cirrhosis and carcinoma.