JANICE ALBRECHT, 12 AND THE HEPATITIS INTERVENTIONAL THERAPY GROUP* with continued therapy at that dose; however, a propor-To evaluate response rates to 3, 5, or 10 million units tion of patients who do not respond to 12 weeks of treat-(MU) of interferon alfa-2b, given thrice weekly, and to ment with 3 or 5 MU may respond to higher doses. Aldetermine whether higher doses of interferon increase though the long-term sustained response rates are the likelihood or durability of the response, a multicenmarginally increased with interferon doses above 3 MU ter, randomized trial was performed at nine academic three times per week, the side effects are difficult to medical centers in the United States. Two hundred forty tolerate. The analysis of baseline factors in relation to eight patients with chronic hepatitis C were randomized response identified no single baseline factor associated to receive 3, 5, or 10 MU of interferon alfa-2b thrice with a low-enough response rate to warrant withholding weekly for 12 weeks. Based on the alanine aminotransinterferon therapy from patients with chronic hepatitis ferase (ALT) response at treatment-week 12, the patients C. (HEPATOLOGY 1996;24:1034-1040.) were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients
Recombinant interferon (IFN) has been shown to be effecwere discontinued from the study. Serum ALT concentive in decreasing serum alanine aminotransferase (ALT) levtrations and liver histology were measured. The overall els, 1-6 in eliminating detectable hepatitis C virus ribonucleic complete response rates to 3, 5, or 10 MU were not differacid (HCV RNA), 7 and in reducing histologic evidence of heent at treatment-week 12 (31% vs. 42% vs. 40%, not signifipatic inflammation in patients with chronic hepatitis C. 1,6 cant). The majority of week-12 responders continued to After nearly a decade of research, however, two major probrespond during additional treatment. When the treatlems with treatment remain. First, a response by the end of ment was discontinued, 15.4% to 19.0% of patients maintreatment occurs in fewer than half of patients. In our previtained their response. Of the nonresponders to 3 MU at ous study, the normalization of the serum ALT levels was week 12, who were continued on 3 MU for an additional seen in 38% of patients treated with a dose of 3 million units 12 weeks, none responded. However, response to addi-(MU) of interferon alfa-2b three times per week for 24 weeks, 1 tional therapy occurred in 12% of week-12 nonrespondand all responding patients achieved their response by treaters, whose dose was escalated from 3 or 5 MU to 10 MU. ment weeks 8 to 12 of treatment. 8 Similar response rates have The only baseline features associated with the treatment now been obtained from several other randomized controlled response were the absence of fibrosis or cirrhosis on studies. [2][3][4][5][6] Second, a response to IFN is usually not mainthe pretreatment liver biopsy and viral genotype. We tained after the drug is stopped, and 50% to 70% of patients conclude that the initial response to interferon in parelapse with the elevation of the serum ALT and HCV RNA tients with chronic hepatitis C is not increased by treatlevels. 1,6 Thus, the ability to achieve and sustain a long-term ment with higher doses of the drug. Patients who do not response to IFN in these patients is only 13% to 25%, with respond to 3 MU by treatment-week 12 will not respond the currently recommended dose regimens. 6 Whether higher initial doses of IFN or the escalation of the dose in nonresponders improves the response to treatment remains contro-Abbreviations: MU, million units; ALT, alanine aminotransferase; IFN, interferon; HCV versial.
RNA, hepatitis C virus ribonucleic acid; ULN, upper limit of normal; HAI, histological Thus, the primary aims of this multicenter study of Ameriactivity index.