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Comparison between ifn induction therapy, IFN induction + Ribavirin and IFN + Ribavirin standard combination therapy in naive patients with chronic hepatitis C related to genotype 1: final report
Poster Sessions
148
HCV RNA (tested by a PCR with a detection limit of 100 copies/rnl) (virological response). Chi square test was used for statistical evaluation. Results: the results are preliminary since 38/40 (95%) pts reached the end of therapy and follow-up of responders is still in progress. Adverse events responsible for treatment withdrawal or doses reductions were observed in 3/20 (15%) pts treated with combination (all severe hemolysis), and in 5/20 pts (25%) (3 depression, 2 thrombocytopenia) treated with C1FN alone. The end therapy responses (ETR) are summarized in the table. End therapy responses Combination Monotherapy
Biochemical Response
Virological Response
14/20 (70%) 9/18 (50%)
11/20 (55%) 6/18 (33.3%)
Conclusions: the preliminary results of this pilot study suggest that the combination of CIFN and Ribavirin is able to induce a virological ETR in more than 50% of naive difficult-to-treat patients with CHC.
~4-~-] COMPARISON BETWEEN IFN INDUCTION THERAPY, IFN INDUCTION + RIBAVIRIN AND IFN + RIBAVIRIN STANDARD COMBINATION THERAPY IN NAIVE PATIENTS WITH CHRONIC HEPATITIS C RELATED TO GENOTYPE 1: FINAL REPORT Antonio Bellobuono, S. Tempini, C. Cattaneo, D. Grimoldi, Andrea Bellobuono, F. Di Berardino, G.M. Idto, G. Idto. Department
of Gastroenterology and Hepatology, S. Giuseppe Hospital, Milan, Italy alFN and Ribavirin (RBV) combination therapy is effective in less than 30% of naive patients (pts) with chronic hepatitis C (CHC) related to genotype 1. Considering the HCV and otlFN kinetics, an induction schedule with daily administration of IFN has been recently suggested. Aim: to compare IFN induction therapy, IFN induction + RBV and standard IFN + RBV combination therapy in naive pts with CHC related to genotype 1. Patients and Treatment: sixty consecutive naive pts affected by biopsyproven CHC related to genotype 1 were randomly treated as follows: 20 pts. with an induction schedule (IFNet2b 5 MU/QID for the 1st month, 5 MU/tiw for 11 months), 20 pts with the same induction schedule plus RBV 1 g/day for 12 months, 20 pts with the combination of IFNet2b 5 MU/tiw and RBV 1 g/day for 12 months. Response to treatment was defined as normalization of serum ALT levels (biochemical response) and negativization of serum HCV RNA (tested by a PCR with a detection limit of 100 copies/ml) (virological response). Chi square test was used for statistical evaluation. Results: early response (after the first month of therapy), end-treatment response (ETR) and Sustained Response (SR) are reported in the table. Biochemical & virological response Induction Induction + RBV IFN + RBV
Early Response
ETR
SR
7/20 (35%) 10/20 (50%) 6/20 (30%)
6/20 (30%) 9/20 (45%) 7/20 (35%)
5/20 (25%) 8/20 (40%) 5/20 (25%)
No significant difference but a trend to a higher efficacy of IFN induction and ribavirin combination treatment was observed. Conclusions: the combination of IFN induction therapy and Ribavirin seemed to be sligthly more effective than both induction IFN monotherapy and IFN + RBV standard combination therapy in naive patients with CHC related to genotype I.
~
PROGRESSION OF FIBROSIS IN CHRONIC HEPATITIS C IN CHILDREN
M. Guido, F. Bortolotti, G. Leo, P. Jara, L. Hierro, G. Leandro, C. Barbera, R. Giacchino, J. Larrauri, L. Zancan, M. Rugge. ULSS 15 -
Veneto, University of Padova., Clinica Medica V, University of Padova; lstituto De Bellis, CasteUana Grotte; Pediatric Department, University of Torino; Department of Infectious Diseases, Gaslini Hospital, Genova; Pediatric Liver, Hospital La Paz, Madrid; Pediatric Department, University of Padova, Italy; Pediatric Liver Unit, Hospital La Paz, Madrid; Pediatric Liver Unit, Hospital La Paz, Madrid, Spain The natural history of fibrosis in chronic hepatitis C acquired in infancy is not known. This study aimed to analyze fibrosis progression in untreated children with chronic HCV infection and no other hepatotoxic factors. Fibrosis was assessed by METAVIR score in 112 pediatric patients (13 with 2 sequential biopsies). The ratio between the stage of fibrosis and the duration of infection represented the "estimated" rate of fibrosis progression per year. In patients with paired biopsies, the "observed" rate of fibrosis progression was defined as the difference between the stage at two consecutive biopsies divided by the interval between the two biopsies. The patient's age at biopsy and the duration of infection strongly correlated with the stage of fibrosis (p < 0.002 and p < 0.0005). The stage of fibrosis differed significantly between patients whose infection had lasted less or more than 10 years (p < 0.0006). Sex, HCV genotype, and route of infection did not correlate with the stage of fibrosis. The stage of fibrosis increased in 7/13 cases with paired biopsies. The difference between estimated and observed fibrosis progression rates in the 13 patients was highly significant, suggesting that predictions based on the estimated fibrosis progression rate were wrong in about 97% of cases. In conclusion, chronic hepatitis C in childhood is a progressive fihrotic disease. Progression is relatively slow and in the absence of co-factors, duration of infection is the only risk factor for severe fibrosis. Fibrosis progression may be discontinuous and the stage may remain unchanged for lengthy periods, making the indirect assessment of the fibrosis progression unreliable.
•7
CIRCULATING LEVELS OF HYALURONIC ACID, PIIINP, METALLOPROTEINASES (MMP-1, MMP-2, MMP-9) AND TISSUE INHIBITORS (TIMP-1 AND TIMP-2) AS SERUM MARKERS OF HEPATIC FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS
V. Leroy, F. Monier, S. Bottari, R. Barnoud, F. Morel, J.P. Zarski.
Hgpato-gastroentdrologie., Biochimie., Biochimie., Anatomopathologie., Biochimie., Grenoble, France Our aim was to evaluate the diagnostic ability of a panel of circulating serum markers. Methods: 192 consecutive chronic hepatitis C patients and 192 age and sex matched controls were studied. The levels of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, HA and PIIINP were determined by ELISA and radio-immuno assay. All dosages were performed from serum collected the same day of the biopsy. Histological activity and fibrosis were staged according to the METAVIR score. Results: Serum levels of MMP-1, MMP-2, MMP-9, HA and PIIINP were significantly higher in CHC patients than in controls. Distribution of fibrosis stage was F0 (n = 32), F1 (n = 72), F2 (n = 48), F3 (n = 22) and F4 (n = 14). MMP-2 (r = 0.28; p < 0.01), TIMP-1 (r = 0.42; p < 0.001), HA (r = 0.50; p < 0.001) and PIIINP (r = 0.62; p < 0.0001) were significantly correlated with fibrosis stage. For each, correlation with activity was lower and disappeared after adjustment to fibrosis. Using ROC analysis, PIIINP was the best marker to detect extensive fibrosis (F3/F4) (area under the curve: 0.88; sensitivity: 92% and specificity: 76% for a threshold of 5 g/ml). For HA and TIMP-1, area under the curve was 0.82 for both (HA > 35 g/ml: sensitivity: 86%, specificity: 60%; TIMP-1 > 1300 g/ml: sensitivity: 75%, specificity: 70%). By
148
HCV RNA (tested by a PCR with a detection limit of 100 copies/rnl) (virological response). Chi square test was used for statistical evaluation. Results: the results are preliminary since 38/40 (95%) pts reached the end of therapy and follow-up of responders is still in progress. Adverse events responsible for treatment withdrawal or doses reductions were observed in 3/20 (15%) pts treated with combination (all severe hemolysis), and in 5/20 pts (25%) (3 depression, 2 thrombocytopenia) treated with C1FN alone. The end therapy responses (ETR) are summarized in the table. End therapy responses Combination Monotherapy
Biochemical Response
Virological Response
14/20 (70%) 9/18 (50%)
11/20 (55%) 6/18 (33.3%)
Conclusions: the preliminary results of this pilot study suggest that the combination of CIFN and Ribavirin is able to induce a virological ETR in more than 50% of naive difficult-to-treat patients with CHC.
~4-~-] COMPARISON BETWEEN IFN INDUCTION THERAPY, IFN INDUCTION + RIBAVIRIN AND IFN + RIBAVIRIN STANDARD COMBINATION THERAPY IN NAIVE PATIENTS WITH CHRONIC HEPATITIS C RELATED TO GENOTYPE 1: FINAL REPORT Antonio Bellobuono, S. Tempini, C. Cattaneo, D. Grimoldi, Andrea Bellobuono, F. Di Berardino, G.M. Idto, G. Idto. Department
of Gastroenterology and Hepatology, S. Giuseppe Hospital, Milan, Italy alFN and Ribavirin (RBV) combination therapy is effective in less than 30% of naive patients (pts) with chronic hepatitis C (CHC) related to genotype 1. Considering the HCV and otlFN kinetics, an induction schedule with daily administration of IFN has been recently suggested. Aim: to compare IFN induction therapy, IFN induction + RBV and standard IFN + RBV combination therapy in naive pts with CHC related to genotype 1. Patients and Treatment: sixty consecutive naive pts affected by biopsyproven CHC related to genotype 1 were randomly treated as follows: 20 pts. with an induction schedule (IFNet2b 5 MU/QID for the 1st month, 5 MU/tiw for 11 months), 20 pts with the same induction schedule plus RBV 1 g/day for 12 months, 20 pts with the combination of IFNet2b 5 MU/tiw and RBV 1 g/day for 12 months. Response to treatment was defined as normalization of serum ALT levels (biochemical response) and negativization of serum HCV RNA (tested by a PCR with a detection limit of 100 copies/ml) (virological response). Chi square test was used for statistical evaluation. Results: early response (after the first month of therapy), end-treatment response (ETR) and Sustained Response (SR) are reported in the table. Biochemical & virological response Induction Induction + RBV IFN + RBV
Early Response
ETR
SR
7/20 (35%) 10/20 (50%) 6/20 (30%)
6/20 (30%) 9/20 (45%) 7/20 (35%)
5/20 (25%) 8/20 (40%) 5/20 (25%)
No significant difference but a trend to a higher efficacy of IFN induction and ribavirin combination treatment was observed. Conclusions: the combination of IFN induction therapy and Ribavirin seemed to be sligthly more effective than both induction IFN monotherapy and IFN + RBV standard combination therapy in naive patients with CHC related to genotype I.
~
PROGRESSION OF FIBROSIS IN CHRONIC HEPATITIS C IN CHILDREN
M. Guido, F. Bortolotti, G. Leo, P. Jara, L. Hierro, G. Leandro, C. Barbera, R. Giacchino, J. Larrauri, L. Zancan, M. Rugge. ULSS 15 -
Veneto, University of Padova., Clinica Medica V, University of Padova; lstituto De Bellis, CasteUana Grotte; Pediatric Department, University of Torino; Department of Infectious Diseases, Gaslini Hospital, Genova; Pediatric Liver, Hospital La Paz, Madrid; Pediatric Department, University of Padova, Italy; Pediatric Liver Unit, Hospital La Paz, Madrid; Pediatric Liver Unit, Hospital La Paz, Madrid, Spain The natural history of fibrosis in chronic hepatitis C acquired in infancy is not known. This study aimed to analyze fibrosis progression in untreated children with chronic HCV infection and no other hepatotoxic factors. Fibrosis was assessed by METAVIR score in 112 pediatric patients (13 with 2 sequential biopsies). The ratio between the stage of fibrosis and the duration of infection represented the "estimated" rate of fibrosis progression per year. In patients with paired biopsies, the "observed" rate of fibrosis progression was defined as the difference between the stage at two consecutive biopsies divided by the interval between the two biopsies. The patient's age at biopsy and the duration of infection strongly correlated with the stage of fibrosis (p < 0.002 and p < 0.0005). The stage of fibrosis differed significantly between patients whose infection had lasted less or more than 10 years (p < 0.0006). Sex, HCV genotype, and route of infection did not correlate with the stage of fibrosis. The stage of fibrosis increased in 7/13 cases with paired biopsies. The difference between estimated and observed fibrosis progression rates in the 13 patients was highly significant, suggesting that predictions based on the estimated fibrosis progression rate were wrong in about 97% of cases. In conclusion, chronic hepatitis C in childhood is a progressive fihrotic disease. Progression is relatively slow and in the absence of co-factors, duration of infection is the only risk factor for severe fibrosis. Fibrosis progression may be discontinuous and the stage may remain unchanged for lengthy periods, making the indirect assessment of the fibrosis progression unreliable.
•7
CIRCULATING LEVELS OF HYALURONIC ACID, PIIINP, METALLOPROTEINASES (MMP-1, MMP-2, MMP-9) AND TISSUE INHIBITORS (TIMP-1 AND TIMP-2) AS SERUM MARKERS OF HEPATIC FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS
V. Leroy, F. Monier, S. Bottari, R. Barnoud, F. Morel, J.P. Zarski.
Hgpato-gastroentdrologie., Biochimie., Biochimie., Anatomopathologie., Biochimie., Grenoble, France Our aim was to evaluate the diagnostic ability of a panel of circulating serum markers. Methods: 192 consecutive chronic hepatitis C patients and 192 age and sex matched controls were studied. The levels of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, HA and PIIINP were determined by ELISA and radio-immuno assay. All dosages were performed from serum collected the same day of the biopsy. Histological activity and fibrosis were staged according to the METAVIR score. Results: Serum levels of MMP-1, MMP-2, MMP-9, HA and PIIINP were significantly higher in CHC patients than in controls. Distribution of fibrosis stage was F0 (n = 32), F1 (n = 72), F2 (n = 48), F3 (n = 22) and F4 (n = 14). MMP-2 (r = 0.28; p < 0.01), TIMP-1 (r = 0.42; p < 0.001), HA (r = 0.50; p < 0.001) and PIIINP (r = 0.62; p < 0.0001) were significantly correlated with fibrosis stage. For each, correlation with activity was lower and disappeared after adjustment to fibrosis. Using ROC analysis, PIIINP was the best marker to detect extensive fibrosis (F3/F4) (area under the curve: 0.88; sensitivity: 92% and specificity: 76% for a threshold of 5 g/ml). For HA and TIMP-1, area under the curve was 0.82 for both (HA > 35 g/ml: sensitivity: 86%, specificity: 60%; TIMP-1 > 1300 g/ml: sensitivity: 75%, specificity: 70%). By