Treatment of chronic hepatitis C with high-dose interferon ?-2b

Abstract

A comparative study of three different high-dose regimens of interferon-alpha-2b (IFN) was conducted in patients with chronic hepatitis C to determine which was better at obtaining a sustained remission. A total of 126 patients were assigned randomly to one of three groups: group A was given 10 million international units (MIU) of IFN six times a week for eight weeks; group B was given 10 MIU IFN six times a week for four weeks followed by three times a week for an additional eight weeks; group C was given 10 MIU IFN six times a week for two weeks followed by three times a week for 12 weeks. The total dose administered to each group was 480 MIU/patient. Only the dosing schedule varied among the three groups. Among 98 efficacy-evaluable patients, a sustained alanine aminotransferase (ALT) response, defined as persistent normalization of the ALT for greater than six months after the termination of treatment, was achieved in 21.2% (7/33) of group A, 42.3% (11/26) of group B, and 54.5% (18/33) of group C patients. Similarly, a sustained loss of measurable serum hepatitis C virus RNA was observed in 28.6% (8/28) of group A, 40.9% (9/22) of group B, and 48.3% (14/29) of group C patients. Based upon these data, it can be concluded that 10 MIU of IFN administered six days a week for two weeks followed by three times a week for an additional 12 weeks produces the highest rate of both biochemical and virological responses to IFN therapy in patients with chronic HCV.

Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: Results of an international randomized controlled trial

“…1,6,7 Numerous randomized trials have demonstrated that from 30% to 65% of hepatitis C patients undergo normalization of alanine aminotransferase (ALT) by the end of a 24-week course of interferon (IFN) treatment. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] IFN treatment improves liver histology 9,12,[16][17][18]21,22 and hepatic function, 6,23 and is associated with loss of HCV RNA from blood and liver in most responders. 14,16,18,[24][25][26][27][28][29][30] As a result of these findings, IFN has become an accepted treatment for hepatitis C. Unfortunately, the initial response is often not sustained.…”

“…13,[17][18][19][20][21][22]28,31 Various approaches have been undertaken to reduce the relapse rate after a 24-week treatment course of IFN. 31,32 These include case selection, higher dose of IFN, 14,15,18,19,21,[33][34][35] increased duration of therapy, 17,18,22,[35][36][37][38] and use of adjunctive agents. [39][40][41] Less attention has been given to possible differences between IFN preparations, although it has been shown that IFN-␥ is ineffective against hepatitis C. 33 The alpha and beta IFNs act through the same cellular receptors.…”

Racial differences in responses to therapy with interferon in chronic hepatitis C

“…There are also marked geographic differences in response rates with highest rates being reported from Japan. 23,24 We have evaluated the possibility that there are racial or ethnic differences in response rates to interferon therapy using data from a large randomized controlled trial of interferon alfa-2b and consensus interferon in a cohort of North American patients with chronic hepatitis C. 9 (group 1) interferon alfa-2b in a dose of 3 million units (MU), or (group 2) consensus interferon in a dose of 9 µg, or (group 3) consensus interferon in a dose of 3 µg, with all groups receiving the interferon by subcutaneous injection three times weekly for 24 weeks. All patients underwent medical evaluation, virological testing, and liver biopsy before therapy.…”

Effect of the Dose and Duration of Interferon-Alpha Therapy on the Incidence of Hepatocellular Carcinoma in Noncirrhotic Patients with a Nonsustained Response to Interferon for Chronic Hepatitis C

“…In Japan, the regimen of IFN therapy is usually intensive; most patients initially receive IFN daily, and the dose of IFN is high (258–800 million units as a total dose) [5, 14, 15, 16, 27]. We hypothesized that this intensive regimen may contribute to the suppressive effect of IFN on the development of HCC in nonsustained responders to IFN.…”