Clinical Gastroenterology Vol.24 No.6(2-6)

Theme Cutting Edge : Pathogenesis and Treatment of Hepatitis B
Title New Nucleoside Analogues for HBV Treatment
Publish Date 2009/06
Author Kazuaki Inoue Division of Gastroenterology, Showa University Fujigaoka Hospital
Author Masaaki Yoshiba Division of Gastroenterology, Showa University Fujigaoka Hospital
[ Summary ] Chronic hepatitis B constitutes a major health problem worldwide. Patients chronically infected with the hepatitis B virus (HBV) can progress to liver cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Active HBV replication is the key driver of hepatitis activity and subsequent disease progression. Therefore, Anti-HBV therapy should suppress HBV replication. Four drugs are currently approved for the treatment of chronic hepatitis B in Japan ; lamivudine, adefovir, entecavir and the interferons. Interferons are injectable drugs that act by inhibiting viral replication and enhancing immune response. The main limitations on the use of interferons are insufficient antiviral effect and poor tolerability. The remaining three agents currently available are orally administered nucleoside analogues that control viral replication. These drugs are generally well tolerated, but their main limitation is the selection of and emergence of antiviral resistance. Tenofovir and clevudine are newly developed nucleoside analogues that have been approved only for use abroad. They have excellent anti-viral effect and high genetic barriers. A major challenge with these excellent drugs is to achieve long-term HBV suppression after cessation of therapy. Immuneactivation is crucial for the enduring suppression of HBV replication. We hope to develop an effective therapeutic vaccine for HBV.
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