Therapeutic activity of vidarabine in symptomatic chronic active hepatitis related to HBV.
The potential inhibitory effects of nucleoside analogues such as ARA-A and acyclovir on HBV-DNA-polymerase were first demonstrated in vitro and then confirmed in vivo in open dose finding studies. The therapeutic efficacy of both ARA-A and ARA-AMP which appeared the most potent drugs was then confirmed by various studies in symptomatic HBeAg-positive patients. These studies demonstrated a similar benefit of therapy with 38 and 40% of treated patients given ARA-A and ARA-AMP, respectively, who permanently cleared HBV replication after a single course, and 67-80% who did so after two courses. Significant improvement in transaminases and histologic activity was also documented (P less than 0.001). Myalgias were observed in 10 and 30% of the patients, respectively. Patients who failed to respond to nucleosides, and those coinfected with HDV, were treated with interferons. Out of 8 cases of HDV/CAH given 5 MU thrice weekly of fibroblast beta-interferon (UPSA) for 3 months, DNA-p activity fell transiently in all 6 initially elevated cases. A parallel decrease in anti-HD titers (P less than or equal to 0.05), inflammation (P less than or equal to 0.001) and necrosis (P less than or equal to 0.05) were observed. alpha-Recombinant interferon was given i.m. for 4 months (2-7 MU/m2 X 2/7 days) to 10 CAH with high DNA-p values. HBV replication was permanently inhibited in 4 cases and dramatically reduced in 3 additional patients. Three failed to respond. Careful monitoring of DNA-p values appeared to be the single most important factor in assessing activity.
D002986:Clinical Trials as Topic; D006509:Hepatitis B / Q000188:drug therapy*; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D006521:Hepatitis, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D011897:Random Allocation; D014740:Vidarabine / Q000627:therapeutic use*; D001084:Vidarabine Phosphate / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D006513:Hepatitis B e Antigens; D001084:Vidarabine Phosphate; D007372:Interferons; D014740:Vidarabine