- Email: [email protected]
[596] GENOTYPE-SPECIFIC ASSESSMENT OF PREDICTIVE FACTORS FOR SUSTAINED VIROLOGIC RESPONSE AFTER STANDARD TREATMENT IN PATIENTS CHRONICALLY INFECTED WITH HCV
POSTERS
S226
was 33.0+1.7 years, mean follow up period after renal TR was 62.0f7.3 month. At the time of renal TR, HCVRNA was positive in 1 I (25.6%) patients, it was negative in 32 (74.4%) patients. HCV reactivation was seen in 19 (45.2%) of patients at the mean time of 20.8f5.7 months after renal TR. In 31 (72%) patients, acute rejection occurred, whereas chronic rejection of the graft kidney had occurred in 10 (23%) patients. Three (7%) patients were died after TR. Out of 43 patients, 22 (51.2%) of them were treated with standard interferon before TR. There was statisticaly significant difference between pretransplant interferon therapy and pretransplant HCVRNA level (p = 0.024). There was no statistically significant difference between HCV reactivation with graft rejection, mortality and graft survival (p > 0.05). Conclusion: HCV reactivation occur in near half of the renal transplant recipients mostly in the second year after TR. Patient survival and graft survival are not affected by HCV reactivation. Anti-HCV positivity should not preclude chronic renal failure patients from renal TR.
15961 GENOTYPE-SPECIFIC ASSESSMENT OF PREDICTIVE FACTORS FOR SUSTAINED VlROLOGlC RESPONSE AFTER STANDARD TREATMENT IN PATIENTS CHRONICALLY INFECTED WITH HCV S. Martens', V Weich', T. Berg', C. Sarrazin3, H. Hinrichsen4, P. Buggisch5, U. Spengler', H. Klinker7, S. Zeuzem3, E. Herrmann'. Fukultiit ,fur Medizin, Innere Medizin, Uniuersitiit des Suurlandes, Honzbnrg-Saur; 'Medizinische Klinik mit S c h ~ w p n n k tHepatologie und Gastroenterologie, Unioersitiitsklinikunz Charite, Cunz[)ns Vircho~iKliniknnz, Berlin; 'Klinik Fur Innere Medizin 1L Uniuersitutsklinikunz dex Saarlandes, Homhurg-Saw; 'Medizinische Uniurr~~itiitsklinik, Kid; "Medizinische linioersitutsklinik Eppendorf; Hanzhurg; Medizinische linioersitutsklinik 11, Bonn: 7Medizinische Klinik und Poliklinik 11 Der Uniuersitut Wurzhurg, Wurzhurg, Germunji E-mail: [email protected]
'
Background: In contrast to patients infected with HCV-GT 1, the predictive value of individual factors for sustained virologic response (SVR) after standard treatment in patients infected with HCV-GT 2.3 is less well understood. Methods: We performed a stepwise multivariate logistic analysis to predict sustained virologic response based on data from patients treated with (pegylated) interferon and ribavirin (GT I .4-6: n = 7 15; GT 2.3: n = 234). The total cohort was randomized in an estimation group and a validation group using a 2: 1 ratio. For the estimation group (n = 632), we estimated the individual chance for SVR using only baseline parameters (Model I ) as well as incorporating serum HCVRNA at week 4 (Model 2) and at week 4 and 12 (Model 3), and checked for possible interactions between genotype and further predictive factors. The models were evaluated by the validation group. Results: The multivariate logistic analysis revealed genotype 2 or 3, young age, low baseline GGT, low serum HCV RNA, high cholesterol, absence of severe tibrosis or cirrhosis as well as high ALT as independent and significant factors for SVR. Interestingly, interactions between genotype and further predictors were not significant indicating comparable influence of the factors on the odds of SVR in patients infected with different HCV genotypes. Evaluation of the models in the validation group yielded area under ROC of 0.77 (Model I), 0.84 (Model 2) and 0.86 (Model 3). See http://www.uniklinikum-saarland.de/hcvresponserechner for an onlinecalculator predicting the individual chance of SVR with the proposed models. Conclusion: We established age, GGT, HCV RNA, cholesterol, absence of severe fibrosis or cirrhosis and ALT as independent factors on SVR in patients infected with HCV GT 1.4-6 and in those infected with HCV GT 2.3. The proposed online-calculator may be valuable for the management of HCV patients.
Model 1
"1 .
T
ROC tune
Model 2 I.a
"1
~
0.0
02
Modell Model2 Model 3
0.4 06 0.8 1 - Specitiuw
1.0
15971 EVOLUTION OF LIVER STIFFNESS MEASUREMENT DURING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C C. Hezode', I. Rosa2, L. Castera', D. Roulot4, V Leroy5, M. BouvierAlias', F. Roudot-Thoraval', C. Douvin', A. Mallat', J-M. Pawlotsky'. Hfipital Henri Mondor; Creteil; Centre hoqiitalier intercommunal, Creteil; H6pital Hunt bueqne, Pessac; 4H6pital Aoicenne, Bohigny; H6pitul A Michallon, Grenoble, Frunce E-mail: [email protected]
'
'
Liver stiffness measurement with the Fibroscan is a non invasive method that assesses the severity of chronic liver disease, in particular fibrosis, in patients with chronic hepatitis C. Whether or not the virologic response to antiviral therapy is associated with concomitant changes in liver stiffness remains unknown. Objective: To assess the dynamics of liver stiffness relative to the dynamics of the virologic response during the first 24 weeks of antiviral therapy in patients with chronic hepatitis C. Methods: 78 patients (57 men, 21 women, mean age: 52+12 years, HCV genotype 1 : 47.5%) with significant fibrosis defined by a liver stiffness measurement >7lcPa were included. 68 patients were treated with the combination of pegylated interferon and ribavirin at the standard doses, whereas 10 untreated patients served as the control group. Liver stiffness and the HCV RNA level were determined at day 0 and at weeks 4, 8, 12, 18 and 24 of therapy. The rapid virologic response (n =40) was detined by a viral load 6 15 TU/mL at week 4. The slow virologic response (n = 17) was defined by a viral load >615 IU/mL at week 4 but 1615 IU/mL at week 24. The nonresponse ( n = 11) was defined by an HCVRNA >6151U/mL at week 24. Results: Liver stiffness at baseline did not differ between the treated and non treated patients. Liver stiffness at baseline was higher in the nonresponders than in the slow and rapid responders, but the difference did not reach significance due to the small number of nonresponders. Liver stiffness did not change significantly in the control group, in the non responders and in the slow responders. In contrast, it decreased significantly i n the rapid responders (13.9 to 12.3, p=0.028). Conclusion: the rapid virologic response to pegylated IFN and ribavirin therapy is associated with a rapid improvement in liver stiffness as measured by the Fibroscan in patients with chronic hepatitis C.
15981 INTERFERON INDUCED GENE INDUCTION AND THE ANTI-VIRAL EFFECTS OF IFN ALPHA IN LIVER BIOPSIES WITH HEPATITIS C: VIRAL AND HOST RESPONSES DETERMINE TREATMENT EFFICACY L. Hibbert, G.R. Foster. Department of Ga.strorntrrologj~,ICMS, London, UK E-mail: [email protected] Background: Therapy for chronic hepatitis C infection (HCV) involves pegylated interferon and ribavirin and is effective in 50% of patients Factors that determine response are unclear some viral strains encode interferon (IFN) inhibitors but the correlation between in vivo effects and therapeutic response is poor Gene chip analysis of peripheral blood cells -
S226
was 33.0+1.7 years, mean follow up period after renal TR was 62.0f7.3 month. At the time of renal TR, HCVRNA was positive in 1 I (25.6%) patients, it was negative in 32 (74.4%) patients. HCV reactivation was seen in 19 (45.2%) of patients at the mean time of 20.8f5.7 months after renal TR. In 31 (72%) patients, acute rejection occurred, whereas chronic rejection of the graft kidney had occurred in 10 (23%) patients. Three (7%) patients were died after TR. Out of 43 patients, 22 (51.2%) of them were treated with standard interferon before TR. There was statisticaly significant difference between pretransplant interferon therapy and pretransplant HCVRNA level (p = 0.024). There was no statistically significant difference between HCV reactivation with graft rejection, mortality and graft survival (p > 0.05). Conclusion: HCV reactivation occur in near half of the renal transplant recipients mostly in the second year after TR. Patient survival and graft survival are not affected by HCV reactivation. Anti-HCV positivity should not preclude chronic renal failure patients from renal TR.
15961 GENOTYPE-SPECIFIC ASSESSMENT OF PREDICTIVE FACTORS FOR SUSTAINED VlROLOGlC RESPONSE AFTER STANDARD TREATMENT IN PATIENTS CHRONICALLY INFECTED WITH HCV S. Martens', V Weich', T. Berg', C. Sarrazin3, H. Hinrichsen4, P. Buggisch5, U. Spengler', H. Klinker7, S. Zeuzem3, E. Herrmann'. Fukultiit ,fur Medizin, Innere Medizin, Uniuersitiit des Suurlandes, Honzbnrg-Saur; 'Medizinische Klinik mit S c h ~ w p n n k tHepatologie und Gastroenterologie, Unioersitiitsklinikunz Charite, Cunz[)ns Vircho~iKliniknnz, Berlin; 'Klinik Fur Innere Medizin 1L Uniuersitutsklinikunz dex Saarlandes, Homhurg-Saw; 'Medizinische Uniurr~~itiitsklinik, Kid; "Medizinische linioersitutsklinik Eppendorf; Hanzhurg; Medizinische linioersitutsklinik 11, Bonn: 7Medizinische Klinik und Poliklinik 11 Der Uniuersitut Wurzhurg, Wurzhurg, Germunji E-mail: [email protected]
'
Background: In contrast to patients infected with HCV-GT 1, the predictive value of individual factors for sustained virologic response (SVR) after standard treatment in patients infected with HCV-GT 2.3 is less well understood. Methods: We performed a stepwise multivariate logistic analysis to predict sustained virologic response based on data from patients treated with (pegylated) interferon and ribavirin (GT I .4-6: n = 7 15; GT 2.3: n = 234). The total cohort was randomized in an estimation group and a validation group using a 2: 1 ratio. For the estimation group (n = 632), we estimated the individual chance for SVR using only baseline parameters (Model I ) as well as incorporating serum HCVRNA at week 4 (Model 2) and at week 4 and 12 (Model 3), and checked for possible interactions between genotype and further predictive factors. The models were evaluated by the validation group. Results: The multivariate logistic analysis revealed genotype 2 or 3, young age, low baseline GGT, low serum HCV RNA, high cholesterol, absence of severe tibrosis or cirrhosis as well as high ALT as independent and significant factors for SVR. Interestingly, interactions between genotype and further predictors were not significant indicating comparable influence of the factors on the odds of SVR in patients infected with different HCV genotypes. Evaluation of the models in the validation group yielded area under ROC of 0.77 (Model I), 0.84 (Model 2) and 0.86 (Model 3). See http://www.uniklinikum-saarland.de/hcvresponserechner for an onlinecalculator predicting the individual chance of SVR with the proposed models. Conclusion: We established age, GGT, HCV RNA, cholesterol, absence of severe fibrosis or cirrhosis and ALT as independent factors on SVR in patients infected with HCV GT 1.4-6 and in those infected with HCV GT 2.3. The proposed online-calculator may be valuable for the management of HCV patients.
Model 1
"1 .
T
ROC tune
Model 2 I.a
"1
~
0.0
02
Modell Model2 Model 3
0.4 06 0.8 1 - Specitiuw
1.0
15971 EVOLUTION OF LIVER STIFFNESS MEASUREMENT DURING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C C. Hezode', I. Rosa2, L. Castera', D. Roulot4, V Leroy5, M. BouvierAlias', F. Roudot-Thoraval', C. Douvin', A. Mallat', J-M. Pawlotsky'. Hfipital Henri Mondor; Creteil; Centre hoqiitalier intercommunal, Creteil; H6pital Hunt bueqne, Pessac; 4H6pital Aoicenne, Bohigny; H6pitul A Michallon, Grenoble, Frunce E-mail: [email protected]
'
'
Liver stiffness measurement with the Fibroscan is a non invasive method that assesses the severity of chronic liver disease, in particular fibrosis, in patients with chronic hepatitis C. Whether or not the virologic response to antiviral therapy is associated with concomitant changes in liver stiffness remains unknown. Objective: To assess the dynamics of liver stiffness relative to the dynamics of the virologic response during the first 24 weeks of antiviral therapy in patients with chronic hepatitis C. Methods: 78 patients (57 men, 21 women, mean age: 52+12 years, HCV genotype 1 : 47.5%) with significant fibrosis defined by a liver stiffness measurement >7lcPa were included. 68 patients were treated with the combination of pegylated interferon and ribavirin at the standard doses, whereas 10 untreated patients served as the control group. Liver stiffness and the HCV RNA level were determined at day 0 and at weeks 4, 8, 12, 18 and 24 of therapy. The rapid virologic response (n =40) was detined by a viral load 6 15 TU/mL at week 4. The slow virologic response (n = 17) was defined by a viral load >615 IU/mL at week 4 but 1615 IU/mL at week 24. The nonresponse ( n = 11) was defined by an HCVRNA >6151U/mL at week 24. Results: Liver stiffness at baseline did not differ between the treated and non treated patients. Liver stiffness at baseline was higher in the nonresponders than in the slow and rapid responders, but the difference did not reach significance due to the small number of nonresponders. Liver stiffness did not change significantly in the control group, in the non responders and in the slow responders. In contrast, it decreased significantly i n the rapid responders (13.9 to 12.3, p=0.028). Conclusion: the rapid virologic response to pegylated IFN and ribavirin therapy is associated with a rapid improvement in liver stiffness as measured by the Fibroscan in patients with chronic hepatitis C.
15981 INTERFERON INDUCED GENE INDUCTION AND THE ANTI-VIRAL EFFECTS OF IFN ALPHA IN LIVER BIOPSIES WITH HEPATITIS C: VIRAL AND HOST RESPONSES DETERMINE TREATMENT EFFICACY L. Hibbert, G.R. Foster. Department of Ga.strorntrrologj~,ICMS, London, UK E-mail: [email protected] Background: Therapy for chronic hepatitis C infection (HCV) involves pegylated interferon and ribavirin and is effective in 50% of patients Factors that determine response are unclear some viral strains encode interferon (IFN) inhibitors but the correlation between in vivo effects and therapeutic response is poor Gene chip analysis of peripheral blood cells -