Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection.
Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.
Colonno
R J
RJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660, USA. richard.colonno@bms.com
Genovesi
E V
EV
Medina
I
I
Lamb
L
L
Durham
S K
SK
Huang
M L
ML
Corey
L
L
Littlejohn
M
M
Locarnini
S
S
Tennant
B C
BC
Rose
B
B
Clark
J M
JM
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000097:blood; D004195:Disease Models, Animal; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000821:virology; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D008392:Marmota; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; C413685:entecavir; D006147:Guanine