High dose interferon alpha-2b therapy for chronic hepatitis C: an open label study of the response and predictors of response.

Abstract

The current recommended dose of interferon (IFN) for chronic hepatitis C is 3 million units (m.u.) 3 times a wk for 6 months, although the optimal dose is uncertain. In an open label cohort format, we evaluated the response rate at 6 months, the relapse rate at 12 months, the predictors of response, and adverse effects in 34 patients (mean age 42.4 +/- 2.4 yr) with chronic hepatitis C who were treated with 5 m.u. IFN 3 times a wk for 6 months. 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 response (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 effects (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 demonstrated 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 performed in six TR and four PR pretreatment, immediately posttreatment, and 3-6 months later. Five TR showed disappearance of viral RNA posttreatment with reappearance at low concentrations in two patients who relapsed. In four PR, viral RNA was detectable at low concentrations posttreatment. 1) Higher dose IFN therapy yields higher response rates at 6 months than the dose currently recommended with acceptable toxicity, but does not improve the sustained response rate; 2) the only predictor of a favorable response in this study was a longer known duration of hepatitis/abnormal ALT elevations; 3) serum HCV-RNA levels often disappear with a total response and may be used to monitor the response to treatment and relapse.