790 TRANSFUSION Volume 44, May 2004 Blackwell Science, LtdOxford, UKTRFTransfusion0041-11322004 American Association of Blood BanksMay 2004445790794Original Article INTERFERON AND RIBAVIRIN THERAPY IN HEMOPHILIA ABBREVIATIONS: BMI = body mass index; IFN = interferon; MU = million unit. From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and the Division of Hepatology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy. Address reprint requests to: Massimo Colombo, MD, Division of Hepatology, IRCCS Maggiore Hospital, Via Pace 9, 20122 Milan, Italy; e-mail: massimo.colombo@unimi.it. Received for publication May 15, 2003; revision received July 31, 2003, and accepted August 5, 2003. TRANSFUSION 2004;44:790-794. TRANSFUSION COMPLICATIONS Sustained suppression of hepatitis C virus by high doses of interferon and ribavirin in adult hemophilic patients E. Santagostino, F. De Filippi, M. G. Rumi, M. Rivi, M. Colombo, and P. M. Mannucci for the Hepatitis Study Group of the Association of Italian Hemophilia Centers BACKGROUND: In a recent randomized controlled study, only a minority (15%) of adult hemophiliacs with chronic HCV achieved a sustained virologic response to treatment with interferon (IFN) and ribavirin given at standard doses. STUDY DESIGN AND METHODS: Whether the therapeutic response might be improved in these patients by increasing the doses of IFN was evaluated. Thirty-four previously untreated, adult hemophiliacs with chronic HCV but negative for HIV were investigated. There were 33 men and 1 woman, aged 21 to 60 years (mean, 36). Twenty-three patients (68%) had genotype 1, and median serum HCV-RNA was 473 ¥ 10 3 IU per L (range, 3.6- 2145). Patients were treated with IFN at 5 million units (MU) thrice weekly for 6 months, followed by 3 mol/L for 6 additional months in combination with daily oral doses of 1 or 1.2 g of ribavirin. RESULTS: A total of 33 patients (97%) completed the study; one patient withdrew because of treatment-related symptoms. Treatment dosage had to be reduced in 20 patients (59%). By intention-to-treat analysis, 14 patients (41%) had a sustained virologic response, particularly those infected by HCV genotype 2 or 3 (70% vs. 29% with genotype 1 or 4, p < 0.05). Sustained response rates were similar in the 13 compliant patients and the 20 patients who had to reduce IFN and/or ribavirin doses (54% vs. 35%). CONCLUSIONS: High-dose IFN therapy plus ribavirin provided high rates of sustained virologic responses in adult hemophiliacs with chronic HCV, even if side-effects led to dose reduction in half of these patients. CV is a major cause of liver-related morbidity and mortality among patients with inherited disorders of coagulation who in the past received large-pool clotting factor concen- trates. 1,2 Recently, a multicenter study in the US showed the good efficacy of combination therapy with interferon alfa (IFN) and ribavirin compared to IFN monotherapy for the treatment of hemophilic patients with chronic HCV. 3 However, when results of this study were stratified by patient age, a sustained virologic response was obtained in only 15 percent of 39 adult patients compared to 59 percent in 17 adolescents with chronic HCV. Thus, age at infection or/and duration of HCV seems to influence IFN responsiveness in hemophilic patients, as it is known for nonhemophilic patients with HCV infection. These two risk factors are likely to interact with other unfavorable predictors of IFN responsiveness that are common among hemophilic patients, such as male sex, genotype 1 of HCV, and high levels of viremia. 4-6 The US study therefore gave the message that therapeutic success with standard doses of combination therapy is substantially restricted to adolescent HCV-infected hemophiliacs (i.e., a category of patients that is disappearing after the introduction of virus-sterilized concentrates in 1985-1987). On the other hand, the US study leaves virtually unresolved the issue of treatment of HCV infection in adult hemophiliacs, the majority of patients at need. Several lines of evidence indicate that increasing the dose of IFN might improve response rates to anti-HCV H