Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: A comparison

Abstract

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.

Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: Correlation with clinical disease stages

“…The level of HCV viremia in serum was assessed by reverse transcription-PCR using conserved 5Ј-noncoding region primers with a sensitivity of 100 copies/mL (National Genetics Institute, Los Angeles). 12 HCV genotyping was performed using the line probe assay as previously described, 13 and HCV genotypes were classified according to the nomenclature of Simmonds et al 14 HCV and Control Antigens. Purified recombinant HCV proteins (derived from genotype 1a sequence) were used: core (aa 1-115), NS3 (aa 1007-1534), and NS4 (aa 1616-1862) (Mikrogen, Munich, Germany).…”

Interferon Alfa-2b in Combination With Ribavirin for the Treatment of Chronic Hepatitis C in Children: Efficacy, Safety, and Pharmacokinetics *

“…10 During the phase 1 study, the initial test of quantitative HCV RNA was replaced by a comparable PCR assay with a detection limit of 100 copies (29 IU)/mL (Schering-Plough); range of linearity 100 to 2 ϫ 10 9 copies/mL. Thereafter, all serum HCV RNA evaluations in the phase 1 and phase 3 studies were performed with the Schering-Plough assay.…”

Estimation of Early Hepatitis C Viral Clearance in Patients Receiving Daily Interferon and Ribavirin Therapy Using A Mathematical Model

“…[4][5][6][7][8] Also, an acute dose response has been reported with higher daily doses of IFN in chronic hepatitis C, and a biphasic exponential viral decline has been described in chronic HCV infection during therapy. [5][6][7] In addition, most patients who achieve a sustained virologic response to antiviral therapy do so early during treatment (in general before week 12), [9][10][11][12][13] and a greater than 3 log reduction in serum HCV RNA early during therapy has been reported to be a good predictor of eventual sustained response. 14 Early clearance of HCV may also theoretically prevent the development of resistant quasispecies.…”