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Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: A UK multicentre study
Posters
I PtCO51531
I P/C06/55
GENOTYPE 4 HCV INFECTION IS ASSOCIATED WITH A POOR RESPONSE TO INTERFERON ALPHA: RESULTS FROM A MATCHED STUDY H. Zylberberg, M.L. Chaix, E Carnot, J.-L. Lagneau, H. Fontaine, S. Pol, C. Brtchot Unit6 d'Htpatologie et INSERM U-370, H6pital Necker, Paris, France. Background/aim: Although HCV type 4 is generally assumed to resist to Interferon therapy, there is still a lack of detailled studies on this issue. Methods : 74 patients out of 1520 (5%) HCV-infected subjects were infected by genotype 4. Response to interferon therapy was analyzed by comparison with HCV lb and 3a infected subjects matched for age, sex, fibrosis score, viral load, doses and duration of interferon therapy. Results: They were 50 men and 24 women with a mean age of 42 + 15 years. The risk factor was transfusion (17 %), IVDU (36 %), origin from endemic country (31%) (Central Africa 48%, Egypte 43%, North Africa 9%) and unknown (16%). Eight were eoinfected by H_IV (11%). Infection through intravenous drug injection was more frequent in french (26/51) than in subjects (1/23) from endemic country (p<0.001). The mean total Knodell and fibrosis scores were of 6.1 ± 4.2 (range: 2-16) and 1.5 + 0.8, respectively. Five patients from endemic countries out of 23 had cirrhosis vs 1/51 from France (p<0.02). Three out of 20 treated patients had cirrhosis and only 5 had a viral load higher than 200 000 copies per ml. Primary and sustained response rate to interferon were significantly lower as compared to patients infected by genotype 3a (10% and 5% vs 85% and 35%; p<0.05) and identical to patients infected by genotype lb (25 et 10% NS) either in patients from France or endemic countries. Conclusion : Our results showed 1. that there are two different genotyp¢ 4 HCV epidemiological profiles i.e. infection from endemic countries and infection through intravenous drug injection, 2. identical poor response to interferon in both suggests intrinsic ability of HCV genotype 4 to resist to interferon therapy. These patients should be treated by reinforced combination therapy.
INTERFERON PLUS AMANTADINE VERSUS INTERFERON ALONE IN THE TREATMENT OF NAIVE PATIENTS WITH CHRONIC HEPATITIS C: A U K MULTICENTRE STUDY S. Caronia l, M.E Bassendine, P. Mills, N. Naumov, R. Fox, J. Lowes, R. Barry, I. Murray-Lyon, G.R. Foster ], the U K Amantadine Study Group Torbay Hospital, Torquay, Bristol Royal Infirmary, Chelsea and Westminster Hospital, London. ]Liver Unit, St Mary's Hospital ICSM London, W21PG, Freeman Hospital, Newcastle, Gartnavel GH, Glasgow, University College, London.
I moe/5, 1
I P/CO 56 I
COMPARISON BETWEEN IFN INDUCTION, INDUCTION+ RIBAVIRIN AND IFN+RIBAVIRIN COMBINATION THERAPY IN NAIVE PATIENTS WITH CHRONIC HEPATITIS C RELATED TO GENOTYPE 1 A. Bellobuono, S. Tempini, G.M. Id~o, D. Grimoldi, P. Brasca, G. Id~o Center for Liver Diseases, S. Giuseppe Hospital, Milan, Italy. IFN and Ribavirin (RBV) combination therapy is effective in about 30% of naive
ESTIMATE OF FIBROSIS PROGRESSION DURING CHRONIC HEPATITIS C (CHC) IN NORTH-EAST ITALY L. Cavalletto, S. Bernardinello, I. Mezzocolli, R. Colombari, A. Favaro, S. Boccato, A. Alberti, A. Gatta, L. Chemello Clinica Medica 5, University of Padova, Italy. ]Anatomia Patologica, University of Verona, Italy.
patientswith chronichepatitisC (CHC) relatedto genstyp¢1. For thesepationts IFlq ind,aion therapyhasbeensu~sted. Aim : to compare IFN inductiontherapy,IYN inductionplus RBV and s * , ~ I ~ and RBV combination thccapyin naive patients with CHC relatedto 8enotyp¢1.
Patients and treatment : sixty consecutive naive patients affected by biopsy-
proven CHC related to geflotype 1 were ran&~y treated as follows: 20 with an induction schedule (IFNcx2b 5 MU/QID for the 1~ month, 5 MU/tiw for 11 months), 20 with the same induaion schedule plus RBV 1 g/day for 12 montl~, 20 with the combination of IFNcz2b 5 MU/tiw and RBV 1 g/day for 12 monhhs. Respo~e to treatment was defined as nornudization of serum ALT levels (biochemical reSlXmS¢)and negan'vizatienof serum HCV RNA (tested by RT PCR with a detection limit of I00 ~pies/ml) (virological response). Chi square test was used for statistical evaluation Retul, : the preliminary results (51160 - 85% of patients reached the end of
therapy)are.,,ummmzedin the table: BIOCHEMICALAND VIROLOGICALRESPONSE Induction ]TN + RBV 10/20 (50%) 7/20 (35%) 6/20 (30%) 9/20 (45%0) 6/20 (30%) 7/20 (35%) 8/18 (44%) 5116 (31%) 5/17 (29%)
Induction+ RBV 1't month 3~ month 12thmonth
Treannem reduction or suspension was needed for side effects in 5 (25%), 6 (30%) and 3 (15%) of patients respectively during induction, induction plus RBV and ]~I + RBV. Conclusion: the combination oflFN induction therapy and Ribavirin seems to be promising in naive patients affected by CHC related to 8enotype 1.
110
I
Aims: Multicentre, randomised trial to assess the efficacy of combination therapy with alpha-Interferon (IFN) plus Amantadine hydrochloride (AMA) compared to Interferon alone in untreated patients with chronic hepatitis C Methods: 180 patients with active chronic HCV Infection were randomised to receive 48 weeks of either IFN (Roferon-4.5 MU/ttw) and AMA (100 nag bd) or IFN alone. Results: The study Is in progress. Response rates at 3, 6 and 12 months in the IFN plus AMA group are 79%, 81% and 50%, compared to 63%, 47% and 23% in the IFN group. Sustained response rates are 47% in the combination therapy group and 21% in the monotherapy group. Drop out rate was 4% in each group and 8% in each group withdrew because of side effects. CONCLUSIONS: Early results suggest that combination therapy with IFN plus AMA is more effective than IFN alone. Also in the UK Amantadlne Studv Gmun: J Morris, Glasgow: D Hollanders, Havering; M Wilkinson, London;S Pugh, Taunton; P Hayes, Edinburgh; M Wiselka, Leicester; M Nelson, London; D Maxwell, London; DC Gleeson, Sheffield.
Fibrosis progression (FP) in CHC is usually assessed by a linear model based on histological stage at one liver biopsy ÷ years of disease duration *[T. Poynard, Lancet 1997;349:825]. To determine the spontaneous liver fibrosis progression rate and risk factors for increasing fibrosis, we evaluated stage difference - past interval of time (yrs) between 2 liver biopsies in 130 cases with CHC (agem46±11; m/f 79151; 52%HCV-1, 43% HCV-2, 5%HCV-3; gradem3.9-J:0.8; stageml.4:L-0.7, 63%F1, 25%F2, 12%F3 by Scheuer score) without cirrhosis or previous antiviral treatment prospectically followed up for 12+8, range 4-20 yrs. Seventy-four% of cases worsened as follows: l°bio~2°bio F1 F2 F1 F3 FI F4 F2 F3 F2 F4 F3 F4
N° 35 12 8 15 12 14
time(ym) 10+6 13+7 15~8 8i-6 13±6 7±2
observed vs.*expected annual FP 0.12i-0.11 0.13+0.04 0.20i-0,16 0.15+0.01 0.24±0.09 0.18±0.02 p=0.01 0.16±0,12 0.18±0.14 0.19~0,04 0.14±0.02 0.17±0.04 0.22+0.12
Cases without progression (27F1,6F2,1F3) showed significantly (p=0.01) lower time interval between 1 ° and 2 ° biopsies (6:l:lyrs). Risk factors by Cox analysis appeared: higher ALT activity and histological grade&stage at 1 ° biopsy (p=0.01). Conclusions: fibrosis progression is not linear but slower dunng the 1 ° decade and quicker thereafter (ratem of annual FP= 0.18, range 0.12-0.24; time to cirrhosis= 17-33 yrs) and depends on biochemical and histological disease activity.
I PtCO51531
I P/C06/55
GENOTYPE 4 HCV INFECTION IS ASSOCIATED WITH A POOR RESPONSE TO INTERFERON ALPHA: RESULTS FROM A MATCHED STUDY H. Zylberberg, M.L. Chaix, E Carnot, J.-L. Lagneau, H. Fontaine, S. Pol, C. Brtchot Unit6 d'Htpatologie et INSERM U-370, H6pital Necker, Paris, France. Background/aim: Although HCV type 4 is generally assumed to resist to Interferon therapy, there is still a lack of detailled studies on this issue. Methods : 74 patients out of 1520 (5%) HCV-infected subjects were infected by genotype 4. Response to interferon therapy was analyzed by comparison with HCV lb and 3a infected subjects matched for age, sex, fibrosis score, viral load, doses and duration of interferon therapy. Results: They were 50 men and 24 women with a mean age of 42 + 15 years. The risk factor was transfusion (17 %), IVDU (36 %), origin from endemic country (31%) (Central Africa 48%, Egypte 43%, North Africa 9%) and unknown (16%). Eight were eoinfected by H_IV (11%). Infection through intravenous drug injection was more frequent in french (26/51) than in subjects (1/23) from endemic country (p<0.001). The mean total Knodell and fibrosis scores were of 6.1 ± 4.2 (range: 2-16) and 1.5 + 0.8, respectively. Five patients from endemic countries out of 23 had cirrhosis vs 1/51 from France (p<0.02). Three out of 20 treated patients had cirrhosis and only 5 had a viral load higher than 200 000 copies per ml. Primary and sustained response rate to interferon were significantly lower as compared to patients infected by genotype 3a (10% and 5% vs 85% and 35%; p<0.05) and identical to patients infected by genotype lb (25 et 10% NS) either in patients from France or endemic countries. Conclusion : Our results showed 1. that there are two different genotyp¢ 4 HCV epidemiological profiles i.e. infection from endemic countries and infection through intravenous drug injection, 2. identical poor response to interferon in both suggests intrinsic ability of HCV genotype 4 to resist to interferon therapy. These patients should be treated by reinforced combination therapy.
INTERFERON PLUS AMANTADINE VERSUS INTERFERON ALONE IN THE TREATMENT OF NAIVE PATIENTS WITH CHRONIC HEPATITIS C: A U K MULTICENTRE STUDY S. Caronia l, M.E Bassendine, P. Mills, N. Naumov, R. Fox, J. Lowes, R. Barry, I. Murray-Lyon, G.R. Foster ], the U K Amantadine Study Group Torbay Hospital, Torquay, Bristol Royal Infirmary, Chelsea and Westminster Hospital, London. ]Liver Unit, St Mary's Hospital ICSM London, W21PG, Freeman Hospital, Newcastle, Gartnavel GH, Glasgow, University College, London.
I moe/5, 1
I P/CO 56 I
COMPARISON BETWEEN IFN INDUCTION, INDUCTION+ RIBAVIRIN AND IFN+RIBAVIRIN COMBINATION THERAPY IN NAIVE PATIENTS WITH CHRONIC HEPATITIS C RELATED TO GENOTYPE 1 A. Bellobuono, S. Tempini, G.M. Id~o, D. Grimoldi, P. Brasca, G. Id~o Center for Liver Diseases, S. Giuseppe Hospital, Milan, Italy. IFN and Ribavirin (RBV) combination therapy is effective in about 30% of naive
ESTIMATE OF FIBROSIS PROGRESSION DURING CHRONIC HEPATITIS C (CHC) IN NORTH-EAST ITALY L. Cavalletto, S. Bernardinello, I. Mezzocolli, R. Colombari, A. Favaro, S. Boccato, A. Alberti, A. Gatta, L. Chemello Clinica Medica 5, University of Padova, Italy. ]Anatomia Patologica, University of Verona, Italy.
patientswith chronichepatitisC (CHC) relatedto genstyp¢1. For thesepationts IFlq ind,aion therapyhasbeensu~sted. Aim : to compare IFN inductiontherapy,IYN inductionplus RBV and s * , ~ I ~ and RBV combination thccapyin naive patients with CHC relatedto 8enotyp¢1.
Patients and treatment : sixty consecutive naive patients affected by biopsy-
proven CHC related to geflotype 1 were ran&~y treated as follows: 20 with an induction schedule (IFNcx2b 5 MU/QID for the 1~ month, 5 MU/tiw for 11 months), 20 with the same induaion schedule plus RBV 1 g/day for 12 montl~, 20 with the combination of IFNcz2b 5 MU/tiw and RBV 1 g/day for 12 monhhs. Respo~e to treatment was defined as nornudization of serum ALT levels (biochemical reSlXmS¢)and negan'vizatienof serum HCV RNA (tested by RT PCR with a detection limit of I00 ~pies/ml) (virological response). Chi square test was used for statistical evaluation Retul, : the preliminary results (51160 - 85% of patients reached the end of
therapy)are.,,ummmzedin the table: BIOCHEMICALAND VIROLOGICALRESPONSE Induction ]TN + RBV 10/20 (50%) 7/20 (35%) 6/20 (30%) 9/20 (45%0) 6/20 (30%) 7/20 (35%) 8/18 (44%) 5116 (31%) 5/17 (29%)
Induction+ RBV 1't month 3~ month 12thmonth
Treannem reduction or suspension was needed for side effects in 5 (25%), 6 (30%) and 3 (15%) of patients respectively during induction, induction plus RBV and ]~I + RBV. Conclusion: the combination oflFN induction therapy and Ribavirin seems to be promising in naive patients affected by CHC related to 8enotype 1.
110
I
Aims: Multicentre, randomised trial to assess the efficacy of combination therapy with alpha-Interferon (IFN) plus Amantadine hydrochloride (AMA) compared to Interferon alone in untreated patients with chronic hepatitis C Methods: 180 patients with active chronic HCV Infection were randomised to receive 48 weeks of either IFN (Roferon-4.5 MU/ttw) and AMA (100 nag bd) or IFN alone. Results: The study Is in progress. Response rates at 3, 6 and 12 months in the IFN plus AMA group are 79%, 81% and 50%, compared to 63%, 47% and 23% in the IFN group. Sustained response rates are 47% in the combination therapy group and 21% in the monotherapy group. Drop out rate was 4% in each group and 8% in each group withdrew because of side effects. CONCLUSIONS: Early results suggest that combination therapy with IFN plus AMA is more effective than IFN alone. Also in the UK Amantadlne Studv Gmun: J Morris, Glasgow: D Hollanders, Havering; M Wilkinson, London;S Pugh, Taunton; P Hayes, Edinburgh; M Wiselka, Leicester; M Nelson, London; D Maxwell, London; DC Gleeson, Sheffield.
Fibrosis progression (FP) in CHC is usually assessed by a linear model based on histological stage at one liver biopsy ÷ years of disease duration *[T. Poynard, Lancet 1997;349:825]. To determine the spontaneous liver fibrosis progression rate and risk factors for increasing fibrosis, we evaluated stage difference - past interval of time (yrs) between 2 liver biopsies in 130 cases with CHC (agem46±11; m/f 79151; 52%HCV-1, 43% HCV-2, 5%HCV-3; gradem3.9-J:0.8; stageml.4:L-0.7, 63%F1, 25%F2, 12%F3 by Scheuer score) without cirrhosis or previous antiviral treatment prospectically followed up for 12+8, range 4-20 yrs. Seventy-four% of cases worsened as follows: l°bio~2°bio F1 F2 F1 F3 FI F4 F2 F3 F2 F4 F3 F4
N° 35 12 8 15 12 14
time(ym) 10+6 13+7 15~8 8i-6 13±6 7±2
observed vs.*expected annual FP 0.12i-0.11 0.13+0.04 0.20i-0,16 0.15+0.01 0.24±0.09 0.18±0.02 p=0.01 0.16±0,12 0.18±0.14 0.19~0,04 0.14±0.02 0.17±0.04 0.22+0.12
Cases without progression (27F1,6F2,1F3) showed significantly (p=0.01) lower time interval between 1 ° and 2 ° biopsies (6:l:lyrs). Risk factors by Cox analysis appeared: higher ALT activity and histological grade&stage at 1 ° biopsy (p=0.01). Conclusions: fibrosis progression is not linear but slower dunng the 1 ° decade and quicker thereafter (ratem of annual FP= 0.18, range 0.12-0.24; time to cirrhosis= 17-33 yrs) and depends on biochemical and histological disease activity.