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510 Efficacy of Peg-interferon alpha-2B (Pegintron) monotherapy in acute hepatitis C: A preliminary analysis
150
Poster Sessions
508 INSULIN RESISTANCE, FIBROSIS AND GENOTYPE ARE PREDICTORS OF SUSTAINED RESPONSE RATE TO PEGYLATED INTERFERON PLUS RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS C
M. Romero-Gomez 1 , M.M. Viloria 2 , R. Corpas 1 , M. Cruz 2 , D. Sanchez-Munoz 1 , L. Grande 1 , J. Castillo 2 , E. Suarez 1 , I. Camacho 2 , M.C. Nogales 3 . 1 Hepatology Unit, 2 Biochemistry Unit, 3 Microbiology Unit, Hospital Universitario de Valme, Sevilla, Spain Aims: To analyze the impact of body composition, leptin system and insulin resistance together with viral factors on sustained viral response in patients with chronic hepatitis C treated with pegylated interferon plus ribavirin (PEG+RIB). Patients and Methods: Patients (n=68;male=38;mean age=43+11) with chronic hepatitis C were treated with PEG+RIB. Genotype 1=47 and non-1=21 patients. Fibrosis (F0-F2=47 patients;F3-F4=21). Leptin levels (Quantikyne), insulin levels (ECLIA) and insulin resistance index [HOMA=Insulin (UI/mL) x serum glucose (mmol/L)/22.5] were measured as were BMI and fat distribution. Results: Patients with SR had a lower BMI (25.7±4.2 vs 28.9±5.1; p=0.01), were younger (40±11 vs 46±10), showed lower serum leptin levels (8.43±7.33 vs 15.81±13.3 ng/ml; p=0.004) and had a lower HOMA (1.9±1.1 vs 4.6± 2.8; p=0.0001). SR was achieved in 44.6% genotype 1 versus 90.5% genotype non-1 (p=0.0001),and 74.5% (35/47) in mild fibrosis vs. 23.8% (5/21) in advanced fibrosis (p=0.001). SR in genotype 1 patients with insulin resistance (HOMA>2) was 23.8% vs 66.6% in genotype 1 patients with normal HOMA; p=0.015. Neither necroinflammatory activity, nor steatosis, nor HSC activation were associated with SR rate. The HOMA, fibrosis and genotype were related with the phase 2 in viral dynamics. In backward logistic multivariate regression analysis, the independent variables related to sustained response were genotype (OR: 5.26; 95%CI=1.53-16.6; p=0.001), HOMA (OR: 2.43; 95%CI=1.01-6.57; p=0.012) and fibrosis (OR: 2.47, 95%CI=1.01-6.03; p=0.029). Conclusions: Insulin resistance, advanced fibrosis and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C, and influence the viral dynamics (phase 2) during treatment with pegylated interferon plus ribavirin.
509 SUSTAINED VIROLOGICAL RESPONSE AFTER PROLONGED TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) (PEGASYS ) AND RIBAVIRIN (COPEGUS ) IN TREATMENT-NAÏVE PATIENTS WITH CHRONIC HEPATITIS C AND DETECTABLE HCV RNA AFTER WEEK 4 OF THERAPY: TERAVIC-4 STUDY
J.M. Sanchez-Tapias 1 , M. Diago 2 , P. Escartin 3 , J. Enriquez 4 , R. Moreno 5 , M. Romero-Gomez 6 , R. Barcena 7 , J. Crespo 8 , R. Andrade 9 . The TeraViC-4 Study Group, Roche, Madrid, Spain; 1 H. Clinic I Provincial, Barcelona, Spain; 2 H. General, Valencia, Spain; 3 H. Puerta Hierro, Madrid, Spain; 4 H. Sant Pau, Barcelona, Spain; 5 H. La Princesa, Madrid, Spain; 6 H. U. Valme, Sevilla, Spain; 7 H. Ramón Y Cajal, Madrid, Spain; 8 H. Marqués Valdecilla, Santander, Spain; 9 H. Virgen Victoria, Málaga, Spain TeraViC-4 targets patients with chronic hepatitis C who do not have very early virological responses after week 4 of therapy (noVR4 = detectable serum HCV RNA >50 IU/ml PCR). Methods: Patients received PEGASYS 180 mcg/week and COPEGUS 800 mg/day. At week 4, PCR(+) patients were randomized to continue either 44 (A, N=165) or 68 (B, N=161) weeks’ treatment. The protocol has been published (Sanchez-Tapias. Methods Find Exp Clin Pharmacol. 2002;24:579-584). SVR was defined as undetectable HCV RNA by the end of the follow-up period in those patients with EOT viral response. Results (table): Baseline characteristics of the randomized groups were similar. Withdrawal rates (17% (A) vs 36% (B)) and the reasons given differed between No-VR4 groups after week 24. Therapy was well-tolerated
and no unexpected adverse events were observed. Longer treatment did not increase the frequency of neutropenia or thrombocytopenia. ITT anaysis (N: A, 165; B, 161) A (48 wks) B (72 wks)
Per protocol analysis (N: A, 116; B, 84)
SVR
No SVR
Missing
Unclassified
SVR
No SVR
30% 36%*
50% 24%
17% 36%
3% 4%
40% 64%†
60% 36%
*p=0.2245, †p=0.0006 for A vs B; N=number of patients in each group.
Conclusions: PEGASYS 180 mcg/week plus COPEGUS 800 mg/day for 72 weeks could offer a better clinical approach for patients with No-VR4, but it obliges the clinician to monitor treatment adherence. The 800 mg/day dose of ribavirin used in the trial has been proven to be optimal in patients infected with HCV genotype 2 or 3, but not in those with genotype 1 who require 1000/1200 mg. This evidence was not established when the trial was initiated.
510 EFFICACY OF PEG-INTERFERON ALPHA-2B (PEGINTRON) MONOTHERAPY IN ACUTE HEPATITIS C: A PRELIMINARY ANALYSIS
T. Santantonio 1 , E. Sinisi 1 , F. Signorile 1 , A. Guastadisegni 1 , C. Casalino 1 , M. Mazzola 2 , R. Francavilla 2 , G. Pastore 1 . 1 Clinic of Infectious Diseases, University of Bari, Bary, Itali; 2 Division of Infectious Diseases, Bisceglie Hospital, Itali IFN monotherapy is effective in reducing the high rate of chronic evolution of acute hepatitis C (AHC), yielding a sustained virological response in 98% of patients treated with daily IFN induction. However, optimal regimen and timing of treatment remain undefined. Our aim was to evaluate the efficacy of pegylated-interferon (Peg-IFN) for 6-months in AHC patients and to verify if treatment response rate is reduced by delaying therapy for 12 weeks, the interval required to exclude patients with spontaneous resolution. Sixteen consecutive patients (diagnosis based on documented anti-HCV seroconversion) viremic after 12 weeks from disease onset, were treated with Peg-IFN-alpha-2b at 1.5 mcg/kg QW for 6 months. Patients (11 males, 5 females, mean age: 36.2 yrs) were HBsAg and anti-HIV negative. Seven patients had genotype 2a/2c, 6 patients gen-1b, and 3 patients gen-3a. Mean HCV RNA and ALT levels at baseline were 316,396±421,476 IU/ml and 256±188 U/l (normal value<40), respectively. At end of treatment, 15/16 (94%) showed virological response, while 14/16 (87%) had normal ALT levels; one of these with slightly increased ALT levels showed normal values after therapy discontinuation. All patients completed 3 months follow-up with virological and biochemical response observed in 15/16 (94%). Ten patients completed 6-months follow-up with a sustained virological and biochemical response in 9/10 (90%). Treatment was welltolerated and no Peg-IFN dose reduction was necessary. These preliminary results show that Peg-IFN-alpha-2b is safe and effective in inducing resolution of acute hepatitis C in almost all treated patients after failure to spontaneously clear HCV infection.
511 EVALUATION OF A NEW, HIGHLY SENSITIVE, REAL TIME PCR BASED ASSAY FOR QUANTIFICATION OF HCV RNA
C. Sarrazin 1 , B. Gartner 2 , M. Welker 1 , S. Traver 1 , S. Zeuzem 1 . 1 Innere Medizin II, Saarland University Clinic, Homburg, Saar, Germany; 2 Department of Virology, Saarland University Clinic, Homburg, Saar, Germany Management of therapy of patients with hepatitis C is based on qualitative and quantitative measurement of HCV-RNA by different assays. A new real-time RT-PCR based assay (COBAS TaqMan, Roche Diagnostics, Pleasanton, USA) was designed for highly sensitive quantification of HCV-RNA thereby covering the range of qualitative and quantitative assays in one test. COBAS TaqMan a single tube, single enzyme, real-
Poster Sessions
508 INSULIN RESISTANCE, FIBROSIS AND GENOTYPE ARE PREDICTORS OF SUSTAINED RESPONSE RATE TO PEGYLATED INTERFERON PLUS RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS C
M. Romero-Gomez 1 , M.M. Viloria 2 , R. Corpas 1 , M. Cruz 2 , D. Sanchez-Munoz 1 , L. Grande 1 , J. Castillo 2 , E. Suarez 1 , I. Camacho 2 , M.C. Nogales 3 . 1 Hepatology Unit, 2 Biochemistry Unit, 3 Microbiology Unit, Hospital Universitario de Valme, Sevilla, Spain Aims: To analyze the impact of body composition, leptin system and insulin resistance together with viral factors on sustained viral response in patients with chronic hepatitis C treated with pegylated interferon plus ribavirin (PEG+RIB). Patients and Methods: Patients (n=68;male=38;mean age=43+11) with chronic hepatitis C were treated with PEG+RIB. Genotype 1=47 and non-1=21 patients. Fibrosis (F0-F2=47 patients;F3-F4=21). Leptin levels (Quantikyne), insulin levels (ECLIA) and insulin resistance index [HOMA=Insulin (UI/mL) x serum glucose (mmol/L)/22.5] were measured as were BMI and fat distribution. Results: Patients with SR had a lower BMI (25.7±4.2 vs 28.9±5.1; p=0.01), were younger (40±11 vs 46±10), showed lower serum leptin levels (8.43±7.33 vs 15.81±13.3 ng/ml; p=0.004) and had a lower HOMA (1.9±1.1 vs 4.6± 2.8; p=0.0001). SR was achieved in 44.6% genotype 1 versus 90.5% genotype non-1 (p=0.0001),and 74.5% (35/47) in mild fibrosis vs. 23.8% (5/21) in advanced fibrosis (p=0.001). SR in genotype 1 patients with insulin resistance (HOMA>2) was 23.8% vs 66.6% in genotype 1 patients with normal HOMA; p=0.015. Neither necroinflammatory activity, nor steatosis, nor HSC activation were associated with SR rate. The HOMA, fibrosis and genotype were related with the phase 2 in viral dynamics. In backward logistic multivariate regression analysis, the independent variables related to sustained response were genotype (OR: 5.26; 95%CI=1.53-16.6; p=0.001), HOMA (OR: 2.43; 95%CI=1.01-6.57; p=0.012) and fibrosis (OR: 2.47, 95%CI=1.01-6.03; p=0.029). Conclusions: Insulin resistance, advanced fibrosis and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C, and influence the viral dynamics (phase 2) during treatment with pegylated interferon plus ribavirin.
509 SUSTAINED VIROLOGICAL RESPONSE AFTER PROLONGED TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) (PEGASYS ) AND RIBAVIRIN (COPEGUS ) IN TREATMENT-NAÏVE PATIENTS WITH CHRONIC HEPATITIS C AND DETECTABLE HCV RNA AFTER WEEK 4 OF THERAPY: TERAVIC-4 STUDY
J.M. Sanchez-Tapias 1 , M. Diago 2 , P. Escartin 3 , J. Enriquez 4 , R. Moreno 5 , M. Romero-Gomez 6 , R. Barcena 7 , J. Crespo 8 , R. Andrade 9 . The TeraViC-4 Study Group, Roche, Madrid, Spain; 1 H. Clinic I Provincial, Barcelona, Spain; 2 H. General, Valencia, Spain; 3 H. Puerta Hierro, Madrid, Spain; 4 H. Sant Pau, Barcelona, Spain; 5 H. La Princesa, Madrid, Spain; 6 H. U. Valme, Sevilla, Spain; 7 H. Ramón Y Cajal, Madrid, Spain; 8 H. Marqués Valdecilla, Santander, Spain; 9 H. Virgen Victoria, Málaga, Spain TeraViC-4 targets patients with chronic hepatitis C who do not have very early virological responses after week 4 of therapy (noVR4 = detectable serum HCV RNA >50 IU/ml PCR). Methods: Patients received PEGASYS 180 mcg/week and COPEGUS 800 mg/day. At week 4, PCR(+) patients were randomized to continue either 44 (A, N=165) or 68 (B, N=161) weeks’ treatment. The protocol has been published (Sanchez-Tapias. Methods Find Exp Clin Pharmacol. 2002;24:579-584). SVR was defined as undetectable HCV RNA by the end of the follow-up period in those patients with EOT viral response. Results (table): Baseline characteristics of the randomized groups were similar. Withdrawal rates (17% (A) vs 36% (B)) and the reasons given differed between No-VR4 groups after week 24. Therapy was well-tolerated
and no unexpected adverse events were observed. Longer treatment did not increase the frequency of neutropenia or thrombocytopenia. ITT anaysis (N: A, 165; B, 161) A (48 wks) B (72 wks)
Per protocol analysis (N: A, 116; B, 84)
SVR
No SVR
Missing
Unclassified
SVR
No SVR
30% 36%*
50% 24%
17% 36%
3% 4%
40% 64%†
60% 36%
*p=0.2245, †p=0.0006 for A vs B; N=number of patients in each group.
Conclusions: PEGASYS 180 mcg/week plus COPEGUS 800 mg/day for 72 weeks could offer a better clinical approach for patients with No-VR4, but it obliges the clinician to monitor treatment adherence. The 800 mg/day dose of ribavirin used in the trial has been proven to be optimal in patients infected with HCV genotype 2 or 3, but not in those with genotype 1 who require 1000/1200 mg. This evidence was not established when the trial was initiated.
510 EFFICACY OF PEG-INTERFERON ALPHA-2B (PEGINTRON) MONOTHERAPY IN ACUTE HEPATITIS C: A PRELIMINARY ANALYSIS
T. Santantonio 1 , E. Sinisi 1 , F. Signorile 1 , A. Guastadisegni 1 , C. Casalino 1 , M. Mazzola 2 , R. Francavilla 2 , G. Pastore 1 . 1 Clinic of Infectious Diseases, University of Bari, Bary, Itali; 2 Division of Infectious Diseases, Bisceglie Hospital, Itali IFN monotherapy is effective in reducing the high rate of chronic evolution of acute hepatitis C (AHC), yielding a sustained virological response in 98% of patients treated with daily IFN induction. However, optimal regimen and timing of treatment remain undefined. Our aim was to evaluate the efficacy of pegylated-interferon (Peg-IFN) for 6-months in AHC patients and to verify if treatment response rate is reduced by delaying therapy for 12 weeks, the interval required to exclude patients with spontaneous resolution. Sixteen consecutive patients (diagnosis based on documented anti-HCV seroconversion) viremic after 12 weeks from disease onset, were treated with Peg-IFN-alpha-2b at 1.5 mcg/kg QW for 6 months. Patients (11 males, 5 females, mean age: 36.2 yrs) were HBsAg and anti-HIV negative. Seven patients had genotype 2a/2c, 6 patients gen-1b, and 3 patients gen-3a. Mean HCV RNA and ALT levels at baseline were 316,396±421,476 IU/ml and 256±188 U/l (normal value<40), respectively. At end of treatment, 15/16 (94%) showed virological response, while 14/16 (87%) had normal ALT levels; one of these with slightly increased ALT levels showed normal values after therapy discontinuation. All patients completed 3 months follow-up with virological and biochemical response observed in 15/16 (94%). Ten patients completed 6-months follow-up with a sustained virological and biochemical response in 9/10 (90%). Treatment was welltolerated and no Peg-IFN dose reduction was necessary. These preliminary results show that Peg-IFN-alpha-2b is safe and effective in inducing resolution of acute hepatitis C in almost all treated patients after failure to spontaneously clear HCV infection.
511 EVALUATION OF A NEW, HIGHLY SENSITIVE, REAL TIME PCR BASED ASSAY FOR QUANTIFICATION OF HCV RNA
C. Sarrazin 1 , B. Gartner 2 , M. Welker 1 , S. Traver 1 , S. Zeuzem 1 . 1 Innere Medizin II, Saarland University Clinic, Homburg, Saar, Germany; 2 Department of Virology, Saarland University Clinic, Homburg, Saar, Germany Management of therapy of patients with hepatitis C is based on qualitative and quantitative measurement of HCV-RNA by different assays. A new real-time RT-PCR based assay (COBAS TaqMan, Roche Diagnostics, Pleasanton, USA) was designed for highly sensitive quantification of HCV-RNA thereby covering the range of qualitative and quantitative assays in one test. COBAS TaqMan a single tube, single enzyme, real-