Chronic Hepatitis B: Individualized Antiviral Therapy

The hepatitis B virus (HBV) was discovered in 1966 with the identification of the Australia antigen in Aboriginals by Dr. Baruch Blumberg, who received the 1976 Nobel Prize in Medicine for his work. We now know the Australia antigen as hepatitis B surface antigen (HBsAg). HBV belongs to a family of closely related DNA viruses called the hepadnaviruses. The viral genome of HBV is a partially double- stranded circular DNA of approximately 3200 base pairs that encodes four overlapping open reading frames: the surface or envelope gene, the core gene, the polymerase gene and the X gene. The core gene can also produce a soluble small molecular weight protein called hepatitis B e antigen (HBeAg) by an alternate start codon and post-translational modification. After entry in the hepatocyte, the HBV DNA is transported to the nucleus and converted to covalently closed circular DNA (cccDNA), which serves as the stable template for transcription of both messenger RNA (for translation of viral proteins) and pre-genomic RNA (for reverse transcription into genomic DNA). Because the cccDNA is highly resistant to antiviral therapy and the host's immunological response, complete eradication of HBV from the liver is probably not feasible.1 HBV is non-cytopathic, cellular injury in HBV infected persons appears immune-mediated.