Background/Aims: To gain understanding of inter-individ-ual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific...Background/Aims: To gain understanding of inter-individ-ual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific T-cell reactivity. Methods: Thirty, treatment-naive HCV-G1 patients received peginter-feron-alfa 2a 180 μg/week plus ribavirin 1000-1200 mg/day, with blood samples collected prospectively at protocol timepoints. HCV RNA was quantitated with a TaqManassay with mathematical modelling of HCV decay. Virus-specific CD4+/CD8+T-cells were enumerated by Elispot assays. Results: HCV kinetic analysis identified two subgroups: fast (18/30) and slow (12/30) treatment-responders. Although these subgroups did not differ in any baseline characteristics, fast responders (FR) showed greater antiviral efficacy (ε)than slow responders (SR) (84.5±3.2 vs. 65.2±7.0%, P=0.002), and a higher rate of infected cell loss (δ) (0.56±0.2 vs. 0.04±0.02, P=0.038). The viral load drop (baseline to treatment week 4) was higher in FR vs. SR group (3.5±1.1 vs. 1.4±0.6 log 10IU/mL, P < 0.001). T-cell reactivity to HCV increased only in FR (after the loss of viraemia), but not in SR patients. Conclusions: Assessment of early viral and T-cell kinetics during treatment reveals marked differences amongst HCV-G1 patients and may provide a basis for treatment individualization. Enhancement of antiviral T-cell reactivity requires rapid viraemia clearance, rather than immunostimulation alone.展开更多
Background/Aims: Therapeutic options for hepatitis C nonresponder patients are limited. Methods: We initiated an open-label pilot study to investigate the efficacy of CIFN plus ribavirin on viral kinetics, sustained v...Background/Aims: Therapeutic options for hepatitis C nonresponder patients are limited. Methods: We initiated an open-label pilot study to investigate the efficacy of CIFN plus ribavirin on viral kinetics, sustained virological response (SVR), and histological response in hepatitis C non-responder patients. Seventy-seven patients were enrolled to receive CIFN given daily in combination with 1000/1200 mg ribavirin. An 8 week induction-dosing regimen of 18 μ g CIFN, followed by 9 μ g for 40 weeks was compared to 9 μ g CIFN for 48 weeks. 90% of patients were infected with HCV-genotype 1. Results: Overall, 82% of the patients demonstrated an early virological response, 65% had an end-of-treatment response, and the SVR was 30% . Interferon/ribavirin non-responders demonstrated a SVR of 22% . Induction-dosing resulted in a greater first-phase HCV-RNA decay that, however, did not translate to better SVRs, presumably due to more dose modifications. High ALT, younger age, and second-phase viral kinetics were associated with SVR. Only sustained responders and relapse patients showed an improved liver histology. Conclusions: Daily dosing of CIFN plus ribavirin may be a promising concept for selected non-responder patients before considering therapies which are anti-viral but not curative. However,motivation and compliance are requisites and a CIFN induction is not required.展开更多
The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters...The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 μg pegylated interferon α-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pre-treatment infected cell loss (δ) (P = .13) but no differences in efficacy of blocking virus production (ε)and infected cell loss during treatment (mδ) compared with patients with elevated ALT levels. Differences were significant for ε(P = .02) and δ(P = .04) when applying updated “healthy”levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters , δ,and mδwas observed in patients with elevated γ-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.展开更多
文摘Background/Aims: To gain understanding of inter-individ-ual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific T-cell reactivity. Methods: Thirty, treatment-naive HCV-G1 patients received peginter-feron-alfa 2a 180 μg/week plus ribavirin 1000-1200 mg/day, with blood samples collected prospectively at protocol timepoints. HCV RNA was quantitated with a TaqManassay with mathematical modelling of HCV decay. Virus-specific CD4+/CD8+T-cells were enumerated by Elispot assays. Results: HCV kinetic analysis identified two subgroups: fast (18/30) and slow (12/30) treatment-responders. Although these subgroups did not differ in any baseline characteristics, fast responders (FR) showed greater antiviral efficacy (ε)than slow responders (SR) (84.5±3.2 vs. 65.2±7.0%, P=0.002), and a higher rate of infected cell loss (δ) (0.56±0.2 vs. 0.04±0.02, P=0.038). The viral load drop (baseline to treatment week 4) was higher in FR vs. SR group (3.5±1.1 vs. 1.4±0.6 log 10IU/mL, P < 0.001). T-cell reactivity to HCV increased only in FR (after the loss of viraemia), but not in SR patients. Conclusions: Assessment of early viral and T-cell kinetics during treatment reveals marked differences amongst HCV-G1 patients and may provide a basis for treatment individualization. Enhancement of antiviral T-cell reactivity requires rapid viraemia clearance, rather than immunostimulation alone.
文摘Background/Aims: Therapeutic options for hepatitis C nonresponder patients are limited. Methods: We initiated an open-label pilot study to investigate the efficacy of CIFN plus ribavirin on viral kinetics, sustained virological response (SVR), and histological response in hepatitis C non-responder patients. Seventy-seven patients were enrolled to receive CIFN given daily in combination with 1000/1200 mg ribavirin. An 8 week induction-dosing regimen of 18 μ g CIFN, followed by 9 μ g for 40 weeks was compared to 9 μ g CIFN for 48 weeks. 90% of patients were infected with HCV-genotype 1. Results: Overall, 82% of the patients demonstrated an early virological response, 65% had an end-of-treatment response, and the SVR was 30% . Interferon/ribavirin non-responders demonstrated a SVR of 22% . Induction-dosing resulted in a greater first-phase HCV-RNA decay that, however, did not translate to better SVRs, presumably due to more dose modifications. High ALT, younger age, and second-phase viral kinetics were associated with SVR. Only sustained responders and relapse patients showed an improved liver histology. Conclusions: Daily dosing of CIFN plus ribavirin may be a promising concept for selected non-responder patients before considering therapies which are anti-viral but not curative. However,motivation and compliance are requisites and a CIFN induction is not required.
文摘The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 μg pegylated interferon α-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pre-treatment infected cell loss (δ) (P = .13) but no differences in efficacy of blocking virus production (ε)and infected cell loss during treatment (mδ) compared with patients with elevated ALT levels. Differences were significant for ε(P = .02) and δ(P = .04) when applying updated “healthy”levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters , δ,and mδwas observed in patients with elevated γ-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.
