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Enhanced PBMC Th1 cytokine production in HCV infected cryoglobulinemic patients
Category 6: Viral hepatitis: clinical aspects suggest, given similar SVR, QoL and safety should be considered principal determinates in the treatment of CHC.
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LONG TERM EVALUATION OF CHILDREN WITH CHRONIC HEPATITIS B AFTER HBeAg/ANTIHBe SEROCONVERSlON CAUSED BY INTERFERON ALPHA TREATMENT
D.M. Lebensztejn, M. Kaczmarski. lllrd Department of Pediatrics,
Medical Academy, Bialystok, Poland The aim of the study was a long-term follow-up of children with chronic hepatitis B after HBeAg/antiHBe seroconversion caused by interferon alpha (IFN) treatment. Patients and Methods: The observation was carried out on 71 children (41 boys and 30 gifts) aged 2-15 yrs with clinically and histopathologically diagnosed chronic hepatitis B, this including 32 children (45%) who were classified as responders at 12 months of follow-up after IFN discontinuation. IFN was applied in the dose of 3 MU 3 T1W for 20 weeks; The evaluation was carried out for 36 months since treatment termination. Results: In the group of responders, IFN alpha caused permanent inhibition of HBV replication measured both with seroconversion in HBeAg/antiHBe system and lack of polimerase HBV DNA activity in blood serum during 36 months follow-up since treatment termination. Progressive normalisation of aminotransferases' activity in blood serum was also observed in this group of children in 81%, 94% and 100% after 12, 24 and 36 months after IFN treatment termination respectively. In spite of the presence of antinuclear antibodies (ANA) and elevation of IgG concentration in blood serum of some patients (about 10% of examined) there was no record of autoimmunological diseases during 36 months observation. Conclusion: Interferon alpha is an efficient and safe drug in treatment of chronic hepatitis B in children and causes permanent inhibition of HBV replication.
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INTERFERON (IFN) INDUCTION FOLLOWED BY PROLONGED HIGH DOSE IFN IN COMBINATION WITH RIBAVIRIN (RBV) FOR RELAPSER HCV PATIENTS: A RANDOMIZED CONTROLLED MULTICENTER TRIAL
G. Fattovich, I. Zagni, G. Fornaciari, E. Minola, P. Fabris, S. Boccia, M. Giusti, G. Abbati, M. Felder, P. Rovere, A. Redaelli, A. Tonon, M. Montanari, C. Paternoster, E. Buscarini, E. Castagnetti, G. Tositti, C. Rizzo, S. Suppressa, M. Pantalena, E Fa. Dept. of Gastroenterology,
147
Four (9%) patients of Group A and 7 (15%) patients of Group B discontinued therapy for side effects. Conclusions: This interin analysis shows an overall sustained response (SR) in 34 (49%) out of 69 patients, a figure comparable to that obtained in relapser patients treated by lower IFN dose (3 MU TIW) plus RBV for 24 weeks (1). However 1 month IFN induction followed by prologed tim of combination Tx with high dose of IFN and RBV tends to improve the SR among genotype ! relapser patients compared to standard combination therapy. References
[1] Davis GL et al. N Engl J Med 1998; 339: 1493-9.
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ENHANCED PBMC TH1 CYTOKINE PRODUCTION IN HCV INFECTED CRYOGLOBULINEMIC PATIENTS
S. Loffreda, L. Muratori, F.B. Bianchi, M. Lenzi. Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Italy HCV-related cryoglobulinemic syndrome, characterized by vasculitis and circulating monoclonal IgM/k rheumatoid factor, is rare and rarely complicates hepatitis C. Cryoglobulinemic patients oft have mild clinical and biochemical manifestations of liver disease, aspects that are influenced by an individual's Thl/Fh2 orientation. Our goal was to document stigmata of differentiate cytokine production. Fifteen chronic HCV infected patients with full blown cryoglobulinemic syndrome were compared to age/sex matched chronic HCV pts, with negative cryocrit. Patients were studied before the initiation of immunosuppressive and/or anti-viral therapy, Cultured PBMCs were stimulated with SAC and supematant cytokine concentrations were measured with commercial ELISAs. The two groups were compared with an unpaired T-test of log transformations. Data reported as mean 5: SE; all p values are <0.0001. The protein concentrations of Thl cytokines ILl2 and ILl8 were significantly greater in the cryoglobulinemic group (430 -4- 210 pg/ml vs. 206 -4- 71 and 661 4- 189 vs. 191 4- 53 respectively). While ILl0, a Th2 cytokine, was greater in the control group (657 5:102 vs. 140 4- 33). The clinical distinctiveness of the two groups is reflected at the cytokine level; the cryoglobulinemics studied have a greater Thl polarization than their cryoglobulin negative counterparts and this may account for the milder liver disease course. Elucidating whether this is linked to circulating immunocomplexes, host or viral factors would give insight into what tips the balance in favor of a Thl response.
University Verona, Verona, Italy Aims: To evaluate the efficacy and safety of IFN u-2b induction therapy (Tx) followed by prolonged time of combination Tx with high dose of IFN u-2b and RBV in relapser (RR) patients with chronic hepatitis C. Patients/Methods: 119 RR patients were randomly assigned to receive an induction schedule with IFN t~ 5 MU daily (Group A: 59 patients) or IFN t~ 5 MU TIW (Group B: 60 patients) for 4 weeks followed by 5 MU TIW and RBV (1000/1200 mg daily) for 44 weeks in both groups A and B. There were no statistical differences for sex, age, presence of cirrhosis or HCV genotypes between the two groups. Results: At present 89 patients have completed 48 weeks Tx and 6 months follow-up is available in 69 and are the subjects of this intreim intention to treat analysis. Percentages of patients with response to Tx (normal ALT and negative serum HCV-RNA) were:
HCV type Group A Group B
1 n=33 53% 56%
End of therapy 2/3 n=56 69% 67%
All n=89 63% 63%
6 months after therapy 1 2/3 All n=27 n---42 n=69 43% 60% 53% 31% 54% 46%
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IFN ALFA-CON 1 + RIBAVIRIN COMBINATION THERAPY IN NAIVE DIFFICULT-TO-TREAT PATIENTS AFFECTED BY CHRONIC HEPATITIS C
Antonio BeUobuono, S. Tempini, D. Grimoldi, L. Mondazzi, G.M. Idto, C. Cattaneo, Andrea Bellobuono, G. Idto. Department of
Gastroenterology and Hepatology, S. Giuseppe Hospital, Milan, Italy IFNct2b and Ribavirin (RBV) combination therapy is effective in less than 28% of naive patients (pts) affected by chronic hepatitis C (CHC), with genotype 1 and high viral load. IFNa CON-1 (CIFN) is a recently developed recombinant type-1 IFN found to be effective in CHC. Aim: we performed a pilot study aimed to evaluate the tolerability and the efficacy of CIFN+ RBV combination therapy as compared with high doses of CIFN alone in naive difficult-to-treat pts. Patients and Treatment: forty consecutive naive pts affected by biopsyproven CHC, with genotype 1 and high viral load (pretreatment serum HCVRNA > 2 x 106 copies/ml) were randomly treated for 48 weeks as follows: 20 pts with CIFN 9/~g/tiw plus RBV 1 g/day, 20 pts with CIFN 18/zg/tiw. Response to treatment was defined as normalization of serum ALT levels (biochemical response) and negativization of serum
~-]
LONG TERM EVALUATION OF CHILDREN WITH CHRONIC HEPATITIS B AFTER HBeAg/ANTIHBe SEROCONVERSlON CAUSED BY INTERFERON ALPHA TREATMENT
D.M. Lebensztejn, M. Kaczmarski. lllrd Department of Pediatrics,
Medical Academy, Bialystok, Poland The aim of the study was a long-term follow-up of children with chronic hepatitis B after HBeAg/antiHBe seroconversion caused by interferon alpha (IFN) treatment. Patients and Methods: The observation was carried out on 71 children (41 boys and 30 gifts) aged 2-15 yrs with clinically and histopathologically diagnosed chronic hepatitis B, this including 32 children (45%) who were classified as responders at 12 months of follow-up after IFN discontinuation. IFN was applied in the dose of 3 MU 3 T1W for 20 weeks; The evaluation was carried out for 36 months since treatment termination. Results: In the group of responders, IFN alpha caused permanent inhibition of HBV replication measured both with seroconversion in HBeAg/antiHBe system and lack of polimerase HBV DNA activity in blood serum during 36 months follow-up since treatment termination. Progressive normalisation of aminotransferases' activity in blood serum was also observed in this group of children in 81%, 94% and 100% after 12, 24 and 36 months after IFN treatment termination respectively. In spite of the presence of antinuclear antibodies (ANA) and elevation of IgG concentration in blood serum of some patients (about 10% of examined) there was no record of autoimmunological diseases during 36 months observation. Conclusion: Interferon alpha is an efficient and safe drug in treatment of chronic hepatitis B in children and causes permanent inhibition of HBV replication.
[-~
INTERFERON (IFN) INDUCTION FOLLOWED BY PROLONGED HIGH DOSE IFN IN COMBINATION WITH RIBAVIRIN (RBV) FOR RELAPSER HCV PATIENTS: A RANDOMIZED CONTROLLED MULTICENTER TRIAL
G. Fattovich, I. Zagni, G. Fornaciari, E. Minola, P. Fabris, S. Boccia, M. Giusti, G. Abbati, M. Felder, P. Rovere, A. Redaelli, A. Tonon, M. Montanari, C. Paternoster, E. Buscarini, E. Castagnetti, G. Tositti, C. Rizzo, S. Suppressa, M. Pantalena, E Fa. Dept. of Gastroenterology,
147
Four (9%) patients of Group A and 7 (15%) patients of Group B discontinued therapy for side effects. Conclusions: This interin analysis shows an overall sustained response (SR) in 34 (49%) out of 69 patients, a figure comparable to that obtained in relapser patients treated by lower IFN dose (3 MU TIW) plus RBV for 24 weeks (1). However 1 month IFN induction followed by prologed tim of combination Tx with high dose of IFN and RBV tends to improve the SR among genotype ! relapser patients compared to standard combination therapy. References
[1] Davis GL et al. N Engl J Med 1998; 339: 1493-9.
[-~
ENHANCED PBMC TH1 CYTOKINE PRODUCTION IN HCV INFECTED CRYOGLOBULINEMIC PATIENTS
S. Loffreda, L. Muratori, F.B. Bianchi, M. Lenzi. Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Italy HCV-related cryoglobulinemic syndrome, characterized by vasculitis and circulating monoclonal IgM/k rheumatoid factor, is rare and rarely complicates hepatitis C. Cryoglobulinemic patients oft have mild clinical and biochemical manifestations of liver disease, aspects that are influenced by an individual's Thl/Fh2 orientation. Our goal was to document stigmata of differentiate cytokine production. Fifteen chronic HCV infected patients with full blown cryoglobulinemic syndrome were compared to age/sex matched chronic HCV pts, with negative cryocrit. Patients were studied before the initiation of immunosuppressive and/or anti-viral therapy, Cultured PBMCs were stimulated with SAC and supematant cytokine concentrations were measured with commercial ELISAs. The two groups were compared with an unpaired T-test of log transformations. Data reported as mean 5: SE; all p values are <0.0001. The protein concentrations of Thl cytokines ILl2 and ILl8 were significantly greater in the cryoglobulinemic group (430 -4- 210 pg/ml vs. 206 -4- 71 and 661 4- 189 vs. 191 4- 53 respectively). While ILl0, a Th2 cytokine, was greater in the control group (657 5:102 vs. 140 4- 33). The clinical distinctiveness of the two groups is reflected at the cytokine level; the cryoglobulinemics studied have a greater Thl polarization than their cryoglobulin negative counterparts and this may account for the milder liver disease course. Elucidating whether this is linked to circulating immunocomplexes, host or viral factors would give insight into what tips the balance in favor of a Thl response.
University Verona, Verona, Italy Aims: To evaluate the efficacy and safety of IFN u-2b induction therapy (Tx) followed by prolonged time of combination Tx with high dose of IFN u-2b and RBV in relapser (RR) patients with chronic hepatitis C. Patients/Methods: 119 RR patients were randomly assigned to receive an induction schedule with IFN t~ 5 MU daily (Group A: 59 patients) or IFN t~ 5 MU TIW (Group B: 60 patients) for 4 weeks followed by 5 MU TIW and RBV (1000/1200 mg daily) for 44 weeks in both groups A and B. There were no statistical differences for sex, age, presence of cirrhosis or HCV genotypes between the two groups. Results: At present 89 patients have completed 48 weeks Tx and 6 months follow-up is available in 69 and are the subjects of this intreim intention to treat analysis. Percentages of patients with response to Tx (normal ALT and negative serum HCV-RNA) were:
HCV type Group A Group B
1 n=33 53% 56%
End of therapy 2/3 n=56 69% 67%
All n=89 63% 63%
6 months after therapy 1 2/3 All n=27 n---42 n=69 43% 60% 53% 31% 54% 46%
--~
IFN ALFA-CON 1 + RIBAVIRIN COMBINATION THERAPY IN NAIVE DIFFICULT-TO-TREAT PATIENTS AFFECTED BY CHRONIC HEPATITIS C
Antonio BeUobuono, S. Tempini, D. Grimoldi, L. Mondazzi, G.M. Idto, C. Cattaneo, Andrea Bellobuono, G. Idto. Department of
Gastroenterology and Hepatology, S. Giuseppe Hospital, Milan, Italy IFNct2b and Ribavirin (RBV) combination therapy is effective in less than 28% of naive patients (pts) affected by chronic hepatitis C (CHC), with genotype 1 and high viral load. IFNa CON-1 (CIFN) is a recently developed recombinant type-1 IFN found to be effective in CHC. Aim: we performed a pilot study aimed to evaluate the tolerability and the efficacy of CIFN+ RBV combination therapy as compared with high doses of CIFN alone in naive difficult-to-treat pts. Patients and Treatment: forty consecutive naive pts affected by biopsyproven CHC, with genotype 1 and high viral load (pretreatment serum HCVRNA > 2 x 106 copies/ml) were randomly treated for 48 weeks as follows: 20 pts with CIFN 9/~g/tiw plus RBV 1 g/day, 20 pts with CIFN 18/zg/tiw. Response to treatment was defined as normalization of serum ALT levels (biochemical response) and negativization of serum