STUDY OBJECTIVE: To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. SETTING:Referral-based liver-disease clinics at three university medical centers. PATIENTS: Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronicactive hepatitis B.
RCT Entities:
STUDY OBJECTIVE: To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. SETTING: Referral-based liver-disease clinics at three university medical centers. PATIENTS: Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.
Authors: P A Furman; M Davis; D C Liotta; M Paff; L W Frick; D J Nelson; R E Dornsife; J A Wurster; L J Wilson; J A Fyfe Journal: Antimicrob Agents Chemother Date: 1992-12 Impact factor: 5.191
Authors: H L Janssen; L Berk; S W Schalm; R A Heijtink; G Hess; S Rossol; K H Meyer zum Buschenfelde; R A Chamuleau; P L Jansen; H W Reesink Journal: Gut Date: 1992-08 Impact factor: 23.059
Authors: P Marcellin; M Pouteau; M A Loriot; N Boyer; F Degos; P Calès; L Bettan; Y Bacq; H Coppére; J D Grange Journal: Gut Date: 1995-03 Impact factor: 23.059