Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.
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).
Han
Yan-Xing
YX
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Xue
Rong
R
Zhao
Wei
W
Zhou
Zhen-Xian
ZX
Li
Jian-Nong
JN
Chen
Hong-Shan
HS
Chen
Xiang-Hong
XH
Wang
Yan-Ling
YL
Li
Yu-Huan
YH
Wu
Yin-Wei
YW
You
Xue-Fu
XF
Zhao
Li-Xun
LX
Jiang
Jian-Dong
JD
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D004359:Drug Therapy, Combination; D005260:Female; D017245:Foscarnet / Q000494:pharmacology / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000998:Antiviral Agents; D019259:Lamivudine; D017245:Foscarnet