Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C

Abstract

To evaluate the efficacy of a 12-month course of recombinant interferon alpha (IFN-alpha2b), and to assess predictive factors of successful response to IFN therapy in chronic active hepatitis C (HCV CAH), 242 patients with histologically proven HCV CAH were assigned randomly to two groups, one treated with IFN-alpha2b (3 MU three times weekly, intramuscularly), the other untreated. To determine the efficacy of IFN-alpha2b 12 months after therapy, a second liver biopsy was carried out on 100 treated patients and 27 untreated patients. The biochemical, virological, and serological response of patients followed up for at least 50 months after treatment was also evaluated to confirm the efficacy of IFN-alpha2b. The genotypes of infecting HCV, anti-HCV core IgM, and HCV-RNA concentrations were also analysed and the predictors of response determined by univariate and multivariate analyses. Response was defined in terms of the normalisation of aminotransferase activities and the disappearance of HCV-RNA. The overall long-term response was 39.4%. Anti-HCV core IgM levels were significantly lower in long-term responders. Patients with increased levels of IgM anti HCV core (>3.8 sample/cut-off), infected with genotype 1b were nonresponders. Liver histology improved significantly in patients with long-term response. Multivariate analysis identified three independent predictors of the likelihood of long-term response to IFN therapy: age younger than 40 years, basal anti-HCV core IgM levels < or = 3.8, and genotypes other than 1b. These data indicate that the treatment with IFN-alpha2b used in this randomised controlled trial is effective in HCV CAH. Anti-HCV core IgM was the strongest predictor of long-term response in the present study.

African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians

“…The most likely explanation is that genotype dominated the outcome. Many previous studies reported that lower serum HCV RNA levels at entry and milder disease correlated with an increase in the probability of response to IFN [13–26]. Since the ETR of African Americans is lower but entry serum HCV RNA is not statistically different from Caucasians, the two factors could combine to explain the observation that entry serum HCV RNA was not a predictive factor in our urban clinic population.…”

“…Serum HCV RNA as measured by PCR methodology is currently used for determining response to therapeutic interventions in patients with CHC. This is based on the concept that elimination of the virus rather than normalization of ALT is the initial goal of therapy [9–14]. Since IFN‐α2b monotherapy can cause unpleasant side‐effects, is expensive, and is associated with a low sustained response rate (SR; 5–10%), defining host or viral parameters that would allow identification of responders or nonresponders prior to the initiation of therapy is a secondary goal of most clinical trials [13–26].…”

Anti-Viral Therapies for Hepatitis C Virus Infection: Current Options and Evolving Candidate Drugs

“…Organ transplant recipient It would appear that younger patients respond better to anti-viral therapy than older patients [39]. Whether this is a function of the relative potency of the immune repertoire at …”

Hepatitis C After Liver Transplantation

“…[49][50][51] The impact of genotype on posttransplant outcome is less clear. Studies differ in terms of diagnostic criteria for severe recurrence, length of follow-up, and end points.…”