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580 Predictive factors of sustained virological and histological response after combination antiviral therapy in transplanted patients with recurrent hepatitis C
05G. Viral Hepatitis'
(g) Hepatitis' C
Methods: The CHASE Project is a large prospective cohort study of an
inner city population (consisting mainly of IDUs) designed to monitor the uptake of health services and to estimate the incidence of communicable infections. All enrolment occurred between January 2003 and December 2004. The cohort data was linked with a longitudinal (1992 2005) laboratory database at the BC Centre for Disease Control that includes HCV antibody and PCR assay results. As part of the baseline survey participants were asked about previous HCV treatment. Results: Overall, 3553 individuals were enrolled, with 2117 having received testing for HCV antibodies. We identified 926 uninfected individuals and documented new infections in 187/940 (19.9%) subjects over a median follow-up of 2.3 years (9.4 cases/100 person-years). In total, 1361 (64.3%) subjects were HCV antibody positive and 798 subjects had received HCV RNA testing. Only 3.4% (46/1361) of HCV antibody positive subjects reported having received treatment for HCV infection. Treatment uptake was similar between whites (3.0%) and Aboriginals (4.1%). A slightly higher percentage of males had received treatment (3.8%) than females (2.5%). Individuals that had received treatment were older (45.2 yrs, standard deviation SD 8.8) when compared to those not having received treatment (41.9 yrs, SD 8.1, p 0.02). Involvement in a methadone maintenance program was not associated with increased HCV treatment initiation. Conclusions: The very low uptake of HCV treatment illustrates the barriers associated with the treatment in IDUs. Given the high prevalence of HCV infection in this population (64.3%), novel treatment interventions are urgently needed in order to cope with the potential future health burden of HCV. Further research is required to identify suitable treatment candidates among IDUs and to develop strategies to overcome barriers to treatment initiation in this population.
F
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EFFECTIVENESS OF ANTIVIRAL T H E R A P Y IN PATIENTS WITH CHRONIC HEPATITIS C TREATED BY GASTROENTEROLOGISTS IN PRIVATE PRACTICE
W.P. Hofmann 1, H. Bock 2, C. Webel2, W. Tacke 2, R. Pfaff2, R. Kihn2, G. Moog 2, H.U. Kellnel 2, M. Sch6fel 2, B. Frick2, R Berg 2, A. Rambow2, M. Friedrich-Rust2, E. Herrmann 1, C. Sarrazin 1, S. Zeuzem 1. 1Saarland
University Hospital, Internal Medicine II, Homburg/Saar, Germany," 2Qualitiitszirkel Gastroenterologie Hessen e. K Frankfitrt am Main, Germany Standard treatment of patients with chronic hepatitis C consists of pegylated interferon (PegIFN) a in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral center. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIFN~2a/ribavirin (n 126) or PegIFN~2b/ribavirin (n 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virologic response was achieved in 54% of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p <0.0001), younger age (p < 0.0001), normal ?-glutamyltransferase levels before initiation of treatment (p 0.003), and absence of language communication problems (p 0.023) were associated with sustained virologic response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p 0.025). Patients infected with HCV genotype 1 in whom the PegIFN~ dose was reduced had higher virological relapse rates (p 0.049). With regard to the treating physician, sustained virologic response rates ranged from 26 67% in patients infected with HCV genotype 1. Our study shows that virologic response rates similar to those in international randomised clinical trials can be achieved by gastroenterologists
Clinical therapy
$215
in private practice. The presented network allows characterization of treatment outcome in chronic hepatitis C not only with regard to virusand host-related factors but also on an individual physician basis.
I-~
PREDICTIVE FACTORS OF SUSTAINED VIROLOGICAL AND HISTOLOGICAL R E S P O N S E AFTER COMBINATION ANTIVIRAL T H E R A P Y IN TRANSPLANTED PATIENTS WITH R E C U R R E N T HEPATITIS C
S. Iacob 1, S. Beckebaum 2, V. Cicinnati 2, R. Iacob 1, L. Gheorghe 1, C. Gheorghe 1, I. Popescu 3, A. Frilling 4, M. Malago 4, G. Gerken 2, C. Broelsch4. 1Center of Gastroenterology and Hepatology, Fundeni
Clinical Institute, Bucharest, Romania," :Department of Gastroenterology and Hepatology, University Hospital Essen, Germany," 3Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bueharest, Romania," 4Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany Background: Hepatitis C virus (HCV) natural history after liver transplantation (LT) is already well known to be more severe than in the nontransplant setting and the efficacy of antiviral therapy is lower than in immunocompetent HCV patients. Aim and Methods: To identify predictive factors of sustained viral response (SVR) and histological response (HR) in HCV patients with recurrent hepatitis C treated with standard or pegylated interferon ~2b and ribavirin 600 800 mg/day. HR is defined as maintenance or improvement of the staging score at 6 months after the end of therapy. Treatment duration was intended for 12 months. Patients were retrospectively analyzed with respect to virus, host and donor related variables, antiviral therapy and immunosuppressive drugs. Univariate and multivariate logistic regression analysis have been conducted. Results: There were 7 females and 28 males with a mean age of 50.6• years at LT. 22.8% of patients had SVR and 42.8% had HR. In the univariate analysis the SVR was associated with: HCV genotype non 1 (p 0.01), ALT value more than 6 times upper normal value at the beginning of therapy (p 0.03), >2log drop of viremia at one month (p 0.0003) and at 3 months (p 0.005), presence of end of therapy biochemical response (EOTBR) (p 0.01) and time elapsed between LT and diagnosis of recurrent hepatitis C <450 days (p 0.04). Male gender (p 0.01), absence of posttransplant biliary complications (p 0.01), >2log decrease of viremia at 3 months (p 0.01), presence of EOTBR (p 0.01), complete one year therapy regimen (p 0.0003) were associated with HR. Multivariate analysis has identified the following independent predictors of SVR: >2log drop of viremia at week 4 (p 0.003), time from LT to first diagnosis of recurrent hepatitis C <450 days (p 0.04) and for HR: absence of biliary complications and one year full antiviral regimen (both p 0.02). Conclusions: A rapid decrease of viremia within the first month of antiviral therapy and a more rapid histological diagnosis after LT are predictive factors for SVR. Biliary complications influence the progression of fibrosis in HCV recipients and one year antiviral therapy is a possible solution for stopping its progression.
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HEPATITIS C VIRUS TREATMENT IN INJECTING DRUG USERS: F R E Q U E N C Y OF CONTRAINDICATIONS AND PROGNOSTIC MARKERS IN PARTICIPANTS OF THE SWISS HEPATITIS C C O H O R T STUDY
S. Dober 1, M. Isler1, D. Meili 1, P. Bruggmann1, Swiss Hepatitis C Cohort Study2. 1ARUD, Ziirieh, Switzerland," 2Swiss Hepatitis' C Cohort
Study, Switzerland Background and Aims: Intravenous drag users (IVDU) are the largest risk group among patients with chronic hepatitis C. Current guidelines give controversial recommendations regarding HCV therapy in IVDU.
(g) Hepatitis' C
Methods: The CHASE Project is a large prospective cohort study of an
inner city population (consisting mainly of IDUs) designed to monitor the uptake of health services and to estimate the incidence of communicable infections. All enrolment occurred between January 2003 and December 2004. The cohort data was linked with a longitudinal (1992 2005) laboratory database at the BC Centre for Disease Control that includes HCV antibody and PCR assay results. As part of the baseline survey participants were asked about previous HCV treatment. Results: Overall, 3553 individuals were enrolled, with 2117 having received testing for HCV antibodies. We identified 926 uninfected individuals and documented new infections in 187/940 (19.9%) subjects over a median follow-up of 2.3 years (9.4 cases/100 person-years). In total, 1361 (64.3%) subjects were HCV antibody positive and 798 subjects had received HCV RNA testing. Only 3.4% (46/1361) of HCV antibody positive subjects reported having received treatment for HCV infection. Treatment uptake was similar between whites (3.0%) and Aboriginals (4.1%). A slightly higher percentage of males had received treatment (3.8%) than females (2.5%). Individuals that had received treatment were older (45.2 yrs, standard deviation SD 8.8) when compared to those not having received treatment (41.9 yrs, SD 8.1, p 0.02). Involvement in a methadone maintenance program was not associated with increased HCV treatment initiation. Conclusions: The very low uptake of HCV treatment illustrates the barriers associated with the treatment in IDUs. Given the high prevalence of HCV infection in this population (64.3%), novel treatment interventions are urgently needed in order to cope with the potential future health burden of HCV. Further research is required to identify suitable treatment candidates among IDUs and to develop strategies to overcome barriers to treatment initiation in this population.
F
•
EFFECTIVENESS OF ANTIVIRAL T H E R A P Y IN PATIENTS WITH CHRONIC HEPATITIS C TREATED BY GASTROENTEROLOGISTS IN PRIVATE PRACTICE
W.P. Hofmann 1, H. Bock 2, C. Webel2, W. Tacke 2, R. Pfaff2, R. Kihn2, G. Moog 2, H.U. Kellnel 2, M. Sch6fel 2, B. Frick2, R Berg 2, A. Rambow2, M. Friedrich-Rust2, E. Herrmann 1, C. Sarrazin 1, S. Zeuzem 1. 1Saarland
University Hospital, Internal Medicine II, Homburg/Saar, Germany," 2Qualitiitszirkel Gastroenterologie Hessen e. K Frankfitrt am Main, Germany Standard treatment of patients with chronic hepatitis C consists of pegylated interferon (PegIFN) a in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral center. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIFN~2a/ribavirin (n 126) or PegIFN~2b/ribavirin (n 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virologic response was achieved in 54% of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p <0.0001), younger age (p < 0.0001), normal ?-glutamyltransferase levels before initiation of treatment (p 0.003), and absence of language communication problems (p 0.023) were associated with sustained virologic response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p 0.025). Patients infected with HCV genotype 1 in whom the PegIFN~ dose was reduced had higher virological relapse rates (p 0.049). With regard to the treating physician, sustained virologic response rates ranged from 26 67% in patients infected with HCV genotype 1. Our study shows that virologic response rates similar to those in international randomised clinical trials can be achieved by gastroenterologists
Clinical therapy
$215
in private practice. The presented network allows characterization of treatment outcome in chronic hepatitis C not only with regard to virusand host-related factors but also on an individual physician basis.
I-~
PREDICTIVE FACTORS OF SUSTAINED VIROLOGICAL AND HISTOLOGICAL R E S P O N S E AFTER COMBINATION ANTIVIRAL T H E R A P Y IN TRANSPLANTED PATIENTS WITH R E C U R R E N T HEPATITIS C
S. Iacob 1, S. Beckebaum 2, V. Cicinnati 2, R. Iacob 1, L. Gheorghe 1, C. Gheorghe 1, I. Popescu 3, A. Frilling 4, M. Malago 4, G. Gerken 2, C. Broelsch4. 1Center of Gastroenterology and Hepatology, Fundeni
Clinical Institute, Bucharest, Romania," :Department of Gastroenterology and Hepatology, University Hospital Essen, Germany," 3Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bueharest, Romania," 4Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany Background: Hepatitis C virus (HCV) natural history after liver transplantation (LT) is already well known to be more severe than in the nontransplant setting and the efficacy of antiviral therapy is lower than in immunocompetent HCV patients. Aim and Methods: To identify predictive factors of sustained viral response (SVR) and histological response (HR) in HCV patients with recurrent hepatitis C treated with standard or pegylated interferon ~2b and ribavirin 600 800 mg/day. HR is defined as maintenance or improvement of the staging score at 6 months after the end of therapy. Treatment duration was intended for 12 months. Patients were retrospectively analyzed with respect to virus, host and donor related variables, antiviral therapy and immunosuppressive drugs. Univariate and multivariate logistic regression analysis have been conducted. Results: There were 7 females and 28 males with a mean age of 50.6• years at LT. 22.8% of patients had SVR and 42.8% had HR. In the univariate analysis the SVR was associated with: HCV genotype non 1 (p 0.01), ALT value more than 6 times upper normal value at the beginning of therapy (p 0.03), >2log drop of viremia at one month (p 0.0003) and at 3 months (p 0.005), presence of end of therapy biochemical response (EOTBR) (p 0.01) and time elapsed between LT and diagnosis of recurrent hepatitis C <450 days (p 0.04). Male gender (p 0.01), absence of posttransplant biliary complications (p 0.01), >2log decrease of viremia at 3 months (p 0.01), presence of EOTBR (p 0.01), complete one year therapy regimen (p 0.0003) were associated with HR. Multivariate analysis has identified the following independent predictors of SVR: >2log drop of viremia at week 4 (p 0.003), time from LT to first diagnosis of recurrent hepatitis C <450 days (p 0.04) and for HR: absence of biliary complications and one year full antiviral regimen (both p 0.02). Conclusions: A rapid decrease of viremia within the first month of antiviral therapy and a more rapid histological diagnosis after LT are predictive factors for SVR. Biliary complications influence the progression of fibrosis in HCV recipients and one year antiviral therapy is a possible solution for stopping its progression.
I•
HEPATITIS C VIRUS TREATMENT IN INJECTING DRUG USERS: F R E Q U E N C Y OF CONTRAINDICATIONS AND PROGNOSTIC MARKERS IN PARTICIPANTS OF THE SWISS HEPATITIS C C O H O R T STUDY
S. Dober 1, M. Isler1, D. Meili 1, P. Bruggmann1, Swiss Hepatitis C Cohort Study2. 1ARUD, Ziirieh, Switzerland," 2Swiss Hepatitis' C Cohort
Study, Switzerland Background and Aims: Intravenous drag users (IVDU) are the largest risk group among patients with chronic hepatitis C. Current guidelines give controversial recommendations regarding HCV therapy in IVDU.