CHRONIC HEPATITIS B (CHB): MOLECULAR PATHOGENESIS, BIOMARKERS, AND ACTIVE MECHANISMS OF THE ANTIVIRUS DRUGS

Objectives: To elucidate the molecular pathogenesis, biomarkers of chronic hepatitis B infection, and mechanisms of action of antiviral drugs. Methods: This study was based on the PRISMA 2020 guidelines to identify, select, evaluate, and synthesize the latest published international research achievements from 2020 to 2026 on the molecular pathogenesis, biomarkers, and mechanisms of action of drugs used to treat chronic HBV infection. Results: Molecular mechanisms of HBV-related pathogenesis include direct mechanisms such as the integration of HBV DNA and the persistent expression of viral proteins like HBx and HBs, which can trigger the expression of oncogenes and cause genetic instability and oxidative stress. Indirect mechanisms include chronic inflammation induced by the host's immune response contributing to the continuous death and regeneration of liver cells, facilitating the appearance of genetic and epigenetic alterations leading to hepatocellular transformation and the progression of HCC. Biomarkers for HBV infection may include screening biomarkers (HBsAg, anti-HBs); diagnostic biomarkers (HBV DNA, ALT, HBeAg, and anti-HBe); treatment monitoring biomarkers (HBV DNA, ALT, and qHBsAg); and prognosis biomarkers (HBcrAg and pgRNA predict recurrence risk; FIB-4 and M2BPGi predict cirrhosis; AFP, AFP-L3, and DCP predict HCC). Current antiviral drugs include nucleotide analogs (NAs) inhibit reverse transcriptase and DNA polymerase, while Peg-IFN inhibits the transcription of cccDNA and modulates the immune response. The new drugs include those that interfere with the viral life cycle, such as entry inhibitors, drugs that directly target cccDNA, drugs that target viral transcripts, antisense oligonucleotides (ASO), capsid assembly inhibitors, and HBsAg secretion inhibitors, as well as drugs that modulate the host immune response, including innate immunity activators, therapeutic vaccines, immune checkpoint inhibitors, T cell immunotherapy, and CTL vaccines. Conclusions: The molecular pathophysiology, biomarkers of chronic hepatitis B infection, and mechanisms of action of antiviral drugs have been elucidated.