HIGH-DOSE INTERFERON-ALPHA-2B THERAPY FOR CHRONIC HEPATITIS-C - AN OPEN-LABEL STUDY OF THE RESPONSE AND PREDICTORS OF RESPONSE

Objectives: The current recommended dose of interferon (IFN) for chron ic hepatitis C is 3 million units (m.u.) 3 times a wk for 6 months, al though the optimal dose is uncertain. In an open label cohort format, we evaluated the response rate at 6 months, the relapse rate at 12 mon ths, the predictors of response, and adverse effects in 34 patients (m ean age 42.4 +/- 2.4 yr) with chronic hepatitis C who were treated wit h 5 m.u. IFN 3 times a wk for 6 months. Results: Twenty-nine patients (85%) responded either totally (TR) or partially (PR), and five (15%) showed no response (NR). Of 18 TR, eight (45%) showed a sustained resp onse (SR), and nine (50%) patients relapsed at 12 months of follow-up with an overall SR rate of 24%. Despite the high frequency of side eff ects (17-70%), all patients completed the treatment. Of interest, two of three PR treated for an additional 3-6 months with 7.5 m.u. of IFN became TR at 12 months. Univariate and multivariate analysis demonstra ted that the known duration of hepatitis and/or abnormal ALT elevation was longer in responders (43.5 +/- 9.1 months) compared with NR (8.2 +/- 1.4 months) (p = 0.018). Age, alcohol abuse, mode of acquisition, transaminase levels, and liver histology did not differ significantly between responders and NR. HCV-RNA in serum by RT-PCR assay was perfor med in six TR and four PR pretreatment, immediately posttreatment, and 3-6 months later. Five TR showed disappearance of viral RNA posttreat ment with reappearance at low concentrations in two patients who relap sed. In four PR, viral RNA was detectable at low concentrations posttr eatment. Conclusions: 1) Higher dose IFN therapy yields higher respons e rates at 6 months than the dose currently recommended with acceptabl e toxicity, but does not improve the sustained response rate; 2) the o nly predictor of a favorable response in this study was a longer known duration of hepatitis/abnormal ALT elevations; 3) serum HCV-RNA level s often disappear with a total response and may be used to monitor the response to treatment and relapse.