GABRIEL GARCIA, M.D.; COLEMAN I. SMITH, M.D.; JED I. WEISSBERG, M.D.; MARK EISENBERG, M.D.; JACK BISSETT, M.D.; PREM V. NAIR, M.D.; BARBARA MASTRE, R.N.; SUE ROSNO, R.N.; DEBBIE ROSKAMP, R.N.; KAREN WATERMAN, R.N.; RICHARD B. POLLARD, M.D.; MYRON J. TONG, MD., Ph.D.; BYRON W. BROWN Jr., Ph.D.; WILLIAM S. ROBINSON, M.D.; PETER B. GREGORY, M.D.; THOMAS C. MERIGAN, M.D.
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.
GARCIA G, SMITH CI, WEISSBERG JI, et al. 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. Ann Intern Med. 1987;107:278–285. doi: 10.7326/0003-4819-107-2-278
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Published: Ann Intern Med. 1987;107(3):278-285.
Gastroenterology/Hepatology, Infectious Disease, Liver Disease.
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