Adenine arabinoside monophosphate (vidarabine phosphate) in combination with human leukocyte interferon in the treatment of chronic hepatitis B. A randomized, double-blinded, placebo-controlled trial.
OBJECTIVE
To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B.


METHODS
Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up.


METHODS
Referral-based liver-disease clinics at three university medical centers.


METHODS
Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis.


METHODS
Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months.


RESULTS
Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis.


CONCLUSIONS
These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.
D000328:Adult; D001088:Arabinonucleotides / Q000627:therapeutic use*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006509:Hepatitis B / Q000473:pathology / Q000628:therapy*; D006515:Hepatitis B virus / Q000302:isolation & purification; D006521:Hepatitis, Chronic / Q000628:therapy; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000628:therapy; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D011897:Random Allocation; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D001088:Arabinonucleotides; D007370:Interferon Type I; D001084:Vidarabine Phosphate