1. Volume 123, Issue 4, Pages 1070-1083 (October 2002)
Peginterferon alone or with ribavirin enhances HCV-specific CD4+ T-helper 1 responses in patients with chronic hepatitis C 
Sanaa M. Kamal, Jutta Fehr, Bernd Roesler, Thomas Peters, Jens W. Rasenack 
Gastroenterology 
Volume 123, Issue 4, Pages (October 2002)
DOI: /gast
Copyright © 2002 American Gastroenterological Association Terms and Conditions

2. Fig. 1
End-of-treatment virologic responses (week 48) and SVR (week 72). (A) Comparison of the outcome of treatment in the 3 patient groups. Group A (▩): IFN α-2a monotherapy (n = 14); group B (■): PEG IFN α-2a monotherapy (n = 14), group C (□): PEG IFN α-2a plus ribavirin (n = 14). End-of-treatment response was 28%, 71%, and 78% in groups A, B, and C, respectively (P = between groups A and B, P = between groups A and C, P = between groups B and C). SVR was 14%, 42%, and 57% in groups A, B, and C, respectively (P = between groups A and B, P < between groups A and C). (B) Response of genotype 1 to the different treatment regimen. The end-of-treatment response was 10%, 50%, and 60% in groups A, B, and C, respectively (P < between groups A and B, P < between groups A and C), whereas SVR was 30% and 48% in groups B and C (P = 0.04). None of genotype 1 patients treated with IFN-α alone achieved SVR. (C) Rates of histologic response at week 72 in 3 patient groups: HAI score represents all patients with both a baseline biopsy examination and end of follow-up biopsy examination (paired). Histologic response is defined as a 2-point improvement in the HAI score. The panels show the histologic response in sustained virologic responders (SVR, n = 16), relapsers and partial responders (R/PR, n = 15), nonresponders (NR = 11), and all patients (n = 42), respectively.Bars represent change from baseline median total HAI score.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

3. Fig. 2
HCV-specific CD4+ proliferative T-cell responses and cytokine production in relation to the virologic profiles for the 3 patient groups at different time intervals. Upper panels: Y1 axis: CD4+ T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI. The cut-off level for a positive response is 3 (3 SD above the mean SI of normal control subjects), which is shown by the horizontal line. Bars represent mean response to a given antigen and lines represent SD. Y2 axis: the mean serum HCV-RNA levels at each time interval before, during, and after therapy. Lower panels show the number of spots representing IFN-γ (●), IL-4 (■), and IL-10 (▴)-secreting cells in the Elispot assay after stimulation with core, error bars = SD. (A) Patients who received IFN α-2a monotherapy (group A), (B) patients who received PEG IFN α-2a monotherapy (group B), (C) patients who received PEG IFN α-2a plus ribavirin (group C).
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Follow-up of ALT, HCV RNA, and HCV-specific CD4+ proliferative T-cell responses and IFN-γ, IL-4, and IL-10 production (Elispot assay) in (A) SVRs (n = 16), (B) partial responders (n = 6) and relapsers (n = 9), and (C) nonresponders (n = 11). Upper panels show the ALT (upper limit of normal, 40 U/L) (●) and the mean serum HCV-RNA levels (♦). Middle panels show CD4+ proliferative T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI (Y axis). The cut-off level for a positive response is 3. Bars represent mean response to a given antigen and lines represent SD. Lower panels show number of spots representing IFN-γ–secreting cells (■), IL-4 (white bars), and the IL-10 (▩)–secreting cells in the Elispot assay after stimulation with core. Bars represent mean response and lines represent SD.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Time course of HCV-specific CD4+ T-cell responses and cytokine production in relation to ALT, HCV RNA, and HAI score in 3 representative sustained responders from the 3 groups. (A) Patient A6 who received IFN α-2a monotherapy. (B) Patient who received PEG IFN α-2a monotherapy. (C) Patient who received PEG IFN α-2a plus ribavirin. Upper panels show the change in HAI score between the baseline biopsy examination and the follow-up liver biopsy examination. The 3 patients showed a histologic response defined as greater than a 2-point decrease in the total HAI score. Middle panels: Y1 axis: CD4+ T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI. The cut-off value for a positive response is 3 (see Materials and Methods section). Y2 axis: mean serum HCV-RNA titers (copies/mL). The 3 sustained responders mounted early, strong responses to at least 2 antigens, which were maintained through follow-up evaluation. Lower panels: Y1 axis: number of T cells/105 cells/well producing IFN-γ–secreting cells (■), IL-4 (□), and IL-10 (▩) in the Elispot assay after stimulation with core. Y2 axis: ALT levels. The 3 patients showed significant preferential IFN-γ production through therapy and follow-up evaluation. The number of IFN-γ SFCs were higher in patients B and C.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Time course of HCV-specific CD4+ T-cell responses and cytokine production in relation to ALT, HCV RNA, and HAI score in 3 representative patients with relapse from the 3 groups. (A) Patient who received IFN α-2a monotherapy. (B) Patient who received PEG IFN α-2a monotherapy. (C) Patient who received PEG IFN α-2a plus ribavirin. Upper panels show the change in HAI score between the baseline biopsy examination and the follow-up liver biopsy examination. A greater than 2-point decrease in HAI score was detected only in patients receiving PEG IFN–based therapies (B and C). Middle panels: Y1 axis: CD4+ T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI. Y2 axis: mean serum HCV-RNA levels at each time-point before, during, and after therapy. HCV-RNA titers at follow-up evaluation were significantly lower than the baseline levels. There was a treatment-induced transient increase in the frequency and strength of CD4+ T-cell responses that paralleled HCV-RNA disappearance. However, the responses declined and were followed by reappearance of viremia, which was lower than pretreatment levels. Lower panels: Y1 axis: number of T cells/105 cells/well producing IFN-γ–secreting cells (■), IL-4 (□), and IL-10 (▩) in the Elispot assay after stimulation with core. Y2 axis: ALT levels.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Time course of HCV-specific CD4+ T-cell responses and cytokine production in relation to ALT, HCV RNA, and HAI score in 3 representative nonresponders from the 3 groups. (A) Patient who received IFN α-2a monotherapy. (B) Patient who received PEG IFN α-2a monotherapy. (C) Patient who received PEG IFN α-2a plus ribavirin. Upper panels show the change in HAI score between the baseline biopsy examination and the follow-up liver biopsy examination. Middle panels: Y1 axis: CD4+ T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI. Y2 axis: mean serum HCV-RNA levels at each time-point before, during, and after therapy. Lower panels: Y1 axis: Number of T cells/105 cells/well producing IFN-γ–secreting cells (■), IL-4 (□), and the IL-10 (▩) in the Elispot assay after stimulation with core. Patients A and C had pretreatment IL-4 and IL-10 production. Therapy was associated with marked suppression of IL-4 and IL-10, which was maintained through follow-up evaluation in patient C, who received PEG IFN/ribavirin therapy. However, IL-4 and IL-10 were detected starting at week 48 in patient A. Y2 axis: ALT levels.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

8. Fig. 7
HCV-specific CD4+ proliferative T-cell responses in relation to histologic response at different time intervals. (A) CD4+ T-cell responses to 4 HCV proteins (core, NS3, NS4, and NS5) expressed as SI (Y axis) in patients who had a greater than 2-point decrease in mean HAI activity scores in their follow-up biopsy examinations. (B) CD4+ T-cell responses in patients who had a less than 2-point decrease in mean HAI activity scores in their follow-up biopsy examinations. Bars represent mean response to a given antigen and lines represent SD. ■, core; □, NS3; ▩, NS4; ▨, NS5.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

9. Fig. 8
Number of IFN-γ (●), IL-4 (■), and IL-10 (▴)–producing cells in response to core, NS3, NS4, and NS5 before induction of (A) antiviral therapy and (B) at 72 weeks. Each symbol represents the response (with the background subtracted) elicited by the HCV antigen in the Elispot assay. X-axis: Patient groups: group A: IFN α-2a monotherapy; group B: PEG IFN α-2a monotherapy; group C: PEG IFN α-2a plus ribavirin; N: control subjects. Y-axis: Significant number of spots (number of spots in wells with HCV antigen minus control wells). Horizontal lines represent means.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions