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Volume 332:1457-1463 June 1, 1995 Number 22 Next

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ABSTRACT

Background We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis.

Methods Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (more than 1.5 times the normal value) for at least one year. All patients were treated for 6 months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one point in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months.

Results Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every 6 months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P<0.001).

Conclusions Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.

Source Information

From the Service d'Hépato-Gastroentérologie, Hôpital Antoine Béclère, Clamart (T.P., J.C.C.); the Service d'Anatomie Pathologique, Hôpital de Bicêtre, Bicêtre (P.B.); Centre National de la Recherche Scientifique, Unité de Recherche Associée 1484, Paris (T.P., P.B., P.M., M.S., J.M.C., M.V.); Institut Pasteur, Lyons (M.C.); Schering–Plough Laboratories, Levallois (C.L.); the Services d'Hépato-Gastroentérologie Hôpital Hotel Dieu, Lyons (C.T.); Hôpital du Haut Lévèque, Pessac (P.C.); Hôpital Régional de Toulouse, Toulouse (J.L.P.); and Hôpital Américain de Paris, Neuilly (M.V., J.M.C.) — all in France.

Address reprint requests to Dr. Poynard at the Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié Salpétrière, 47-83 Boulevard de l'Hôpital, 75651 Paris CEDEX 13, France.

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