Differential effect of ARA-AMP on serum DNA polymerase activity and serum HBV-DNA in chronic hepatitis B virus infection. A possible reason for lack of efficacy.
An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an hepatoma). Of the remaining 13, 11 remained HBeAg-positive at 1 year. During treatment, the median serum DNA polymerase (DNAp) activity fell from 592 cpm to 203 cpm/200 microliters. Of 12 patients initially positive for DNA polymerase, complete inhibition during treatment occurred in 6 and was permanent in 2, who developed anti-HBe. In the remaining 4 and in 6 further patients in whom inhibition was substantial but incomplete, DNAp activity rose to pretreatment levels within 1 month of completing treatment. All these patients remained DNAp + HBeAg-positive at one year. Serum HBV-DNA was measured in 7 patients, 6 who were initially DNAp-positive and 4 of whom had complete inhibition of DNAp during treatment. All 7 remained positive for HBV-DNA during treatment. Although side-effects were common there were no significant changes in biochemical or haematological parameters during or subsequent to therapy. Over the subsequent 48 months 2 more patients have developed an hepatoma and a further 5 have lost HBeAg; the 4 patients who remain alive and HBeAg-positive all had chronic persistent hepatitis initially.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001088:Arabinonucleotides / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D004259:DNA-Directed DNA Polymerase / Q000097:blood*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006521:Hepatitis, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013997:Time Factors; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
D001088:Arabinonucleotides; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D001084:Vidarabine Phosphate; D004259:DNA-Directed DNA Polymerase