| Theme | Hepatitis B Update 2004 | |
|---|---|---|
| Title | Nucleoside Analogue for Treatment of Breakthrough Hepatitis Caused by Lamivudine Resistant Mutations of Hepatitis B Virus | |
| Publish Date | 2004/10 | |
| Author | Yoshiyuki Suzuki | Department of Gastroenterology, Toranomon Hospital |
| Author | Hiromitsu Kumada | Department of Gastroenterology, Toranomon Hospital |
| [ Summary ] | Lamivudine is an oral nucleoside analogue with potent antiviral activity. It prohibits the replication of the hepatitis B virus (HBV), and induces strong antiviral activity as well as improvements in liver function in patients with chronic hepatitis B. Since the therapeutic efficacy of lamivudine is reflected most reliably by histological improvement, this has been regarded as the ´gold standard´ in evaluating treatment response. However, the emergence of lamivudine resistant HBV strains in patients on long term lamivudine therapy has been observed, and such resistant mutation occurs in the HBV DNA polymerase gene. The emergence of such mutant viruses results in the reelevation of HBV DNA and ALT, and causes clinical and histologic progression. Mutants resistant to lamivudine emerged in parallel with the duration of lamivudine, as reported by others. Adefovir dipivoxil (ADV) and Entecavir (ETV) are nucleoside analogues that selectively inhibit viral polymerases and reverse transcriptases. These drugs display antiviral activity against not only wild type HBV but also lamivudine resistant HBV mutations. In these studies, the administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ETV reduced HBV DNA and ALT levels in patients with breakthrough hepatitis. |
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