In this overview, Tatyana Kushner, MD, reviews key aspects of hepatitis B pathophysiology with a focus on covalently closed circular DNA (cccDNA) and its role in viral persistence and barriers to cure. She explains how cccDNA is established and maintained within hepatocytes, how host epigenetic regulation influences viral transcription, and why current antiviral therapies are unable to eliminate cccDNA. The discussion highlights emerging cure strategies, including epigenetic silencing, direct cccDNA targeting, gene-editing technologies, and host factor modulation. Dr. Kushner also explores immune-viral interactions in chronic hepatitis B, including immune exhaustion and checkpoint pathways, as well as clinically relevant extrahepatic manifestations and diagnostic considerations. The video concludes with an overview of hepatitis B genotypes and their impact on disease progression, hepatocellular carcinoma risk, and therapeutic response.
