A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C

Abstract

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Hepatitis viruses under immunosuppressive agents

“…They found the same reciprocal changes of serum HCV-RNA and ALT in nine (or 90%) of the patients. Similar changes of HCV-RNA and ALT were also observed by Chayama et al 56 using prednisolone 40mglday for 3 weeks in a randomized controlled study. Apart from these serum markers, a study in chimpanzees also demonstrated a massive increase of HCV antigen (HCVAg) in association with minimal histological changes during immunosuppression, but was also followed by clearance of liver HCVAg and serum HCV-RNA after withdrawal of immunosupp r e~s i o n .~~ Given this observation, it is conceivable that the immune and clinical rebound after withdrawal of immunosuppressants could be extremely severe and lead to hepatic failure.…”