- Email: [email protected]
634 IMPACT OF THE DRUG USE AND SUBSTITUTION TREATMENTS ON THE ANTIVIRAL TREATMENT OF CHRONIC HEPATITIS C: ANALYSIS OF ADHERENCE, VIROLOGICAL RESPONSE AND QUALITY OF LIFE
05g: VIRAL HEPATITIS − g) HEPATITIS C − CLINICAL (THERAPY) SVR was undetectable serum HCV-RNA at the end of 6-month posttreatment follow-up. HCV-RNA measurements were performed with VERSANTR HCV 3.0 Assay (bDNA) (Siemens), and VERSANTR HCV RNA Qualitative Assay (TMA) (Siemmens) (bDNA/TMA); Cobas Ampliprep/Cobas TaqMan (CAP/CTM) (Roche Molecular Systems); Abbott m2000sp extraction/m2 000rt amplification system (ART) (Abbott Laboratories). Low BVL was <400,000 IU/ml (PPV), RVR was defined as undetectable serum HCV RNA or 2 log drop decline of BVL at week 4 (PPV) and non-EVR was defined as detectable serum HCV RNA or log drop <2 log decline of BLV at week 12 (NPV) of therapy. Results: The median BLV were: 5.56 (2.60−6.82), 5.19 (2.80−7.48) and 4.63 (2.23−6.58), with bDNA/TMA, CAP/CTM and ART, respectively (p < 0.001). Conclusions: Monitoring of therapy should include both, detection of serum HCV RNA at week 4 to predict SVR and at week 12 to predict non-SVR. Both 3 assays show the same performance to evaluate RVR or non-EVR. However, assays show viral load discrepancy according to HCV genotype, it is therefore important to consistently use the same HCV RNA assay through out treatment patient follow-up. PPV Baseline viral load
NPV Week 4
Week 12
400,000 IU/ml Undetectable 2 log drop Detectable <2 log drop
bDNA/TMA 59% CAP/CTM 57% ART 55%
97% 91% 94%
68% 70% 70%
85% 92% 81%
93% 84% 74%
633 EVALUATION OF A PREDICTIVE MODEL OF INDIVIDUAL CHANCE FOR SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN S. Mauss1 , D. Hueppe2 , E. Zehnter3 , S. Richter4 , A. Tappe5 , E. Herrmann4 . 1 Center of Gastroenterology and Hepatology, Duesseldorf, 2 Center of Gastroenterology, Herne, 3 Center of Gastroenterology, Dortmund, 4 Klinikum der Johann Wolfgang Goethe Universitaet, Frankfurt, 5 Roche Pharma AG, Grenzach-Wyhlen, Germany E-mail: [email protected] Background: Success of HCV treatment is known to be dependent on various factors. By counseling a patient before therapy these variables play a crucial role. For this a response calculator based on baseline variables as well as RVR and EVR may be helpful to guide treatment decisions. Methods: Recently, Martens et al presented a response calculator derived from data of 949 patients treated in various German multi-center clinical trials. Three models were proposed using defined baseline factors and, if available, serum HCV RNA at week 4 and week 12 to predict sustained virological response (SVR) for individual patients. The models showed good predictive values for patients treated under study conditions (area under ROC 0.77, 0.84 and 0.86, respectively). We applied the proposed response calculator on data of 7266 patients included in a nationwide observational study conducted by the Association of German Gastroenterologists in Private Practice (bng) together with Roche to evaluate the predictive value of this calculator for an unselected cohort of patients treated with Peginterferon alfa-2a and ribavirin under real life conditions. Results: Evaluation of the model in this cohort yielded an area under ROC of 0.67. Evaluation in defined subgroups (GT 1/4/5/6, GT 2/3, HCV RNA /> 400,000 IU/mL, age />40 years, total cholesterol />180 mg/dL, fibrosis yes/no, GPT normal/high, GGT normal/high) demonstrated that these factors were addressed adequately by the algorithm. Furthermore, potential factors not included in the prediction (with/without concomitant diseases, with/without HIV co-infection, with/without diabetes mellitus, IVDU yes/no, patients with essential hypertension) showed similar area under ROC values with consistently lower rates of SVR for all analyzed populations. This indicates comparable
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predictive value for all these subgroups of patients and a lower probability of SVR in this real life cohort (overall SVR rate was 48.2% in the observational study compared with 59.6% in the study patients). Conclusion: Evaluation of a response calculator derived from study data in an unselected cohort showed a lower predictive value than for study patients. Under routine clinical practice additional factors resulting from lesser patient selection may influence treatment success and further analysis is necessary to include these factors in the model. 634 IMPACT OF THE DRUG USE AND SUBSTITUTION TREATMENTS ON THE ANTIVIRAL TREATMENT OF CHRONIC HEPATITIS C: ANALYSIS OF ADHERENCE, VIROLOGICAL RESPONSE AND QUALITY OF LIFE P. Melin1 , J.-P. Lang2 , D. Ouzan3 , M. Chousterman4 , M. Varastet5 , M. Rotily5 , T. Fontanges6 , P. Marcellin7 , P. Cacoub8 . 1 Hˆopital G´en´eral, Saint Dizier, 2 Centre Hospitalier Erstein, Erstein, 3 Institut Arnaud Tzanck, Saint Laurent du Var, 4 Hˆopital de Cr´eteil, Cr´eteil, 5 ClinSearch, Bagneux, 6 Centre de l’Appareil Digestif, Bourgoin Jallieu, 7 Hˆopital Beaujon, Clichy, 8 Hˆopital Piti´e-Salpˆetri`ere AP HP, Paris, France E-mail: [email protected] Background and Aims: CHEOBS is a French multicenter, prospective, observational study that aimed to analyse the factors associated with adherence to treatment with peginterferon alfa-2b and ribavirin in chronic hepatitis C patients. The present analysis focuses on adherence to antiviral dual therapy, virological response, and quality of life (QoL) according to whether the patients were active drug users or under substitution treatment (ADU), ex-drug users (EDU), or non-drug users (NDU). Patients and Methods: Between 2003 and 2006, 184 clinicians evaluated 2001 hepatitis C patients every 3 months during treatment and 6 months after the end of treatment. Among these patients, 141 were excluded from the analysis. The studied population included 244 ADU, 578 EDU and 1038 NDU. Good adherence was defined by >80% of the dose and duration of the antiviral dual therapy prescribed. Sustained virological response (SVR) was defined by a negative PCR 12 weeks after the end of treatment. QoL was assessed using the SF-36 questionnaire. Results: The patient profile in the EDU group was between that in the ADU and NDU groups for mean age, body mass index (BMI), liver fibrosis, level of education or debt difficult to manage, high consumption of alcohol, psychiatric disorders, or chronic diseases. The proportion of good adherents to dual therapy was similar in all three groups: NDU, 49.4%; EDU, 48.6%; ADU, 52.2% (p = 0.7). The SVR rate was also similar: 49.3%, 50.9%, and 57.8%, respectively (p = 0.1). The QoL in the ADU group was less altered on the physical and mental levels than in the other groups. Conclusions: The rate of SVR was similar in the three groups. Excess consumption of alcohol, a precarious socioeconomic situation, and the psychiatric disorders observed in drug users in this study had no negative impact on the treatment outcomes. On the contrary, young age, recent contamination, high prevalence of genotype 3 infection, lower BMI, less severe liver fibrosis, and good adherence to treatment seem to have balanced the negative parameters. 635 INSULIN RESISTANCE AND GEOGRAPHICAL ORIGIN ARE MAJOR PREDICTORS OF LIVER FIBROSIS AND RESPONSE TO PEGYLATED INTERFERON AND RIBAVIRIN IN GENOTYPE 4 CHRONIC HEPATITIS C PATIENTS R. Moucari, M.-P. Ripault, M. Martinot-Peignoux, C. Castelnau, H. Voitot, A. El Ray, T. Asselah, N. Boyer, M. Vidaud, P. Bedossa, D. Valla, P. Marcellin. Beaujon Hospital, Clichy, France E-mail: [email protected] Background and Aim: HCV genotype 4 (HCV-4) is increasing in prevalence in Europe. However, little is known about the severity of the disease and response to treatment. The aim of this study was to assess the
NPV Week 4
Week 12
400,000 IU/ml Undetectable 2 log drop Detectable <2 log drop
bDNA/TMA 59% CAP/CTM 57% ART 55%
97% 91% 94%
68% 70% 70%
85% 92% 81%
93% 84% 74%
633 EVALUATION OF A PREDICTIVE MODEL OF INDIVIDUAL CHANCE FOR SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN S. Mauss1 , D. Hueppe2 , E. Zehnter3 , S. Richter4 , A. Tappe5 , E. Herrmann4 . 1 Center of Gastroenterology and Hepatology, Duesseldorf, 2 Center of Gastroenterology, Herne, 3 Center of Gastroenterology, Dortmund, 4 Klinikum der Johann Wolfgang Goethe Universitaet, Frankfurt, 5 Roche Pharma AG, Grenzach-Wyhlen, Germany E-mail: [email protected] Background: Success of HCV treatment is known to be dependent on various factors. By counseling a patient before therapy these variables play a crucial role. For this a response calculator based on baseline variables as well as RVR and EVR may be helpful to guide treatment decisions. Methods: Recently, Martens et al presented a response calculator derived from data of 949 patients treated in various German multi-center clinical trials. Three models were proposed using defined baseline factors and, if available, serum HCV RNA at week 4 and week 12 to predict sustained virological response (SVR) for individual patients. The models showed good predictive values for patients treated under study conditions (area under ROC 0.77, 0.84 and 0.86, respectively). We applied the proposed response calculator on data of 7266 patients included in a nationwide observational study conducted by the Association of German Gastroenterologists in Private Practice (bng) together with Roche to evaluate the predictive value of this calculator for an unselected cohort of patients treated with Peginterferon alfa-2a and ribavirin under real life conditions. Results: Evaluation of the model in this cohort yielded an area under ROC of 0.67. Evaluation in defined subgroups (GT 1/4/5/6, GT 2/3, HCV RNA /> 400,000 IU/mL, age />40 years, total cholesterol />180 mg/dL, fibrosis yes/no, GPT normal/high, GGT normal/high) demonstrated that these factors were addressed adequately by the algorithm. Furthermore, potential factors not included in the prediction (with/without concomitant diseases, with/without HIV co-infection, with/without diabetes mellitus, IVDU yes/no, patients with essential hypertension) showed similar area under ROC values with consistently lower rates of SVR for all analyzed populations. This indicates comparable
S233
predictive value for all these subgroups of patients and a lower probability of SVR in this real life cohort (overall SVR rate was 48.2% in the observational study compared with 59.6% in the study patients). Conclusion: Evaluation of a response calculator derived from study data in an unselected cohort showed a lower predictive value than for study patients. Under routine clinical practice additional factors resulting from lesser patient selection may influence treatment success and further analysis is necessary to include these factors in the model. 634 IMPACT OF THE DRUG USE AND SUBSTITUTION TREATMENTS ON THE ANTIVIRAL TREATMENT OF CHRONIC HEPATITIS C: ANALYSIS OF ADHERENCE, VIROLOGICAL RESPONSE AND QUALITY OF LIFE P. Melin1 , J.-P. Lang2 , D. Ouzan3 , M. Chousterman4 , M. Varastet5 , M. Rotily5 , T. Fontanges6 , P. Marcellin7 , P. Cacoub8 . 1 Hˆopital G´en´eral, Saint Dizier, 2 Centre Hospitalier Erstein, Erstein, 3 Institut Arnaud Tzanck, Saint Laurent du Var, 4 Hˆopital de Cr´eteil, Cr´eteil, 5 ClinSearch, Bagneux, 6 Centre de l’Appareil Digestif, Bourgoin Jallieu, 7 Hˆopital Beaujon, Clichy, 8 Hˆopital Piti´e-Salpˆetri`ere AP HP, Paris, France E-mail: [email protected] Background and Aims: CHEOBS is a French multicenter, prospective, observational study that aimed to analyse the factors associated with adherence to treatment with peginterferon alfa-2b and ribavirin in chronic hepatitis C patients. The present analysis focuses on adherence to antiviral dual therapy, virological response, and quality of life (QoL) according to whether the patients were active drug users or under substitution treatment (ADU), ex-drug users (EDU), or non-drug users (NDU). Patients and Methods: Between 2003 and 2006, 184 clinicians evaluated 2001 hepatitis C patients every 3 months during treatment and 6 months after the end of treatment. Among these patients, 141 were excluded from the analysis. The studied population included 244 ADU, 578 EDU and 1038 NDU. Good adherence was defined by >80% of the dose and duration of the antiviral dual therapy prescribed. Sustained virological response (SVR) was defined by a negative PCR 12 weeks after the end of treatment. QoL was assessed using the SF-36 questionnaire. Results: The patient profile in the EDU group was between that in the ADU and NDU groups for mean age, body mass index (BMI), liver fibrosis, level of education or debt difficult to manage, high consumption of alcohol, psychiatric disorders, or chronic diseases. The proportion of good adherents to dual therapy was similar in all three groups: NDU, 49.4%; EDU, 48.6%; ADU, 52.2% (p = 0.7). The SVR rate was also similar: 49.3%, 50.9%, and 57.8%, respectively (p = 0.1). The QoL in the ADU group was less altered on the physical and mental levels than in the other groups. Conclusions: The rate of SVR was similar in the three groups. Excess consumption of alcohol, a precarious socioeconomic situation, and the psychiatric disorders observed in drug users in this study had no negative impact on the treatment outcomes. On the contrary, young age, recent contamination, high prevalence of genotype 3 infection, lower BMI, less severe liver fibrosis, and good adherence to treatment seem to have balanced the negative parameters. 635 INSULIN RESISTANCE AND GEOGRAPHICAL ORIGIN ARE MAJOR PREDICTORS OF LIVER FIBROSIS AND RESPONSE TO PEGYLATED INTERFERON AND RIBAVIRIN IN GENOTYPE 4 CHRONIC HEPATITIS C PATIENTS R. Moucari, M.-P. Ripault, M. Martinot-Peignoux, C. Castelnau, H. Voitot, A. El Ray, T. Asselah, N. Boyer, M. Vidaud, P. Bedossa, D. Valla, P. Marcellin. Beaujon Hospital, Clichy, France E-mail: [email protected] Background and Aim: HCV genotype 4 (HCV-4) is increasing in prevalence in Europe. However, little is known about the severity of the disease and response to treatment. The aim of this study was to assess the