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

Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?

The availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be licensed in the short term. Treatment is generally recommended for patients with high serum HBV DNA and elevated ALAT, indicating the host's immune response against HBV. Induction of an HBV -specific immune response seems crucial for persistent control of HBV infection. Currently available treatment strategies can be differentiated into those that provide sustained off-treatment response and those that provide therapy maintained response. A finite treatment course with immunomodulatory agents (interferon-based therapy) results in sustained response in about one third of patients, while nucleoside analogue treatment generally requires indefinite therapy without a clear stopping point. Since nucleoside analogues are well tolerated, prolonged therapy is feasible, but a major drawback is the considerable risk of developing antiviral resistance, which occurs most frequently in lamivudine treated patients and to a lesser extent during adefovir or entecavir therapy. In our opinion, treatment with peginterferon should therefore be considered first-line therapy in eligible patients with a high likelihood of response based on serum HBV DNA, ALAT and HBV genotype. Patients not responding to PEG-IF N therapy or not eligible for peginterferon therapy should be treated with nucleos(t)ide analogues