Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.

Abstract

Foscarnet (PFA), a viral DNA polymerase inhibitor, is a clinical agent for herpes viruses. The goal of the study was to evaluate the therapeutic efficacy of PFA in hepatitis B virus (HBV) infection. Intravenous infusion of PFA (1 g/day) for 4 weeks significantly reduced serum HBeAg (p<0.01) and HBV DNA copies (p<0.05) in 31 patients who were diagnosed with active chronic HBV infection (CHB) and had not received antiviral treatment previously. Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and gamma glutamyl transpeptidase (gamma-GT) of the patients declined (p<0.001, 0.001 and 0.01, respectively). Kidney function (blood creatinine and urea nitrogen) remained unchanged. Another 21 lamivudine-resistant CHB patients with mutations at the tyrosine-methionine-aspartate-aspartate motif (YMDD) displayed a response to PFA similar to that mentioned above, with reductions in HBeAg (p<0.05), HBV DNA (p<0.01) and liver enzymes (ALT and AST, p<0.001; gamma-GT, p<0.05). Moreover, PFA reduced serum HBeAg (p<0.01), HBV DNA (P<0.05), AST (p<0.05) and ALT (p<0.02) in a cohort of 13 severe CHB patients with advanced liver damage. PFA was also evaluated in vitro and in vivo. PFA inhibited HBV DNA replication in HBV-transfected human HepG2 cells (2.2.15 cells) with reduced amount of HBV RC-DNA and DS-DNA. In the duck HBV-infected ducklings, PFA reduced viral DNA and duck HBsAg in the serum (p<0.01 for both).

• Authors: Yan-Xing Han, Rong Xue, Wei Zhao, Zhen-Xian Zhou, Jian-Nong Li, Hong-Shan Chen, Xiang-Hong Chen, Yan-Ling Wang, Yu-Huan Li, Yin-Wei Wu, Xue-Fu You, Li-Xun Zhao, Jian-Dong Jiang
• Journal: Antiviral research (Antiviral Res) Vol. 68 Issue 3 Pg. 147-53 (Dec 2005) ISSN: 0166-3542 [Print] Netherlands
• PMID: 16280177 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Lamivudine
• Foscarnet

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Cell Culture Techniques
• Drug Therapy, Combination
• Female
• Foscarnet (pharmacology, therapeutic use)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy, physiopathology)
• Humans
• Lamivudine (pharmacology)
• Male
• Middle Aged
• Treatment Outcome