578 Uptake of hepatitis C virus (HCV) treatment among injection drug users (IDUS) in Vancouver, Canada

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cirrhosis/advanced fibrosis and the overall population. Fixed-dose induction Peg-IFNa-2a(40KD) was more effective than standard-dose PegIFN~-2a (40KD) over the first 12 weeks. Patients with cirrhosis/advanced fibrosis were less likely to have a virological response than the overall population, regardless of Peg-IFN~-2a(40KD) dose during weeks 1 12. Both doses were well-tolerated. 180 gg/week (Arms C+D)

360 gg/week (Arms A+B)

Cil-r/adv fib

Overall pop

Cil-r/adv fib

Overall pop

Patients, n a

133

469

119

473

Male, n (%) Age • yrs Caucasian, n (%) HCV genotype 1, n (%) HCV RNA • • 106 IU/InL EVR at week 12b Discontinuation for safety reasons

102 (77) 51.1• 119 (89) 121 (91) 5.2• 50 (38) 3 (2)

319 (68) 48.8• 413 (88) 425 (91) 4.9• 210 (45) 11 (2)

80 (67) 51.7• 110 (92) 108 (91) 4.5• 60 (50) 5 (4)

297 (63) 48.3• 418(88) 429 (91) 5.4• 291 (62)* 9 (2)

~>1 AE/SAE 121(91)/6(5) 430(92)/19(4) 112(94)/4(3) 441(93)/10(2) Peg-IFNc>2a(40KD) dose mod or disc 21 (16) 63 (13) 30 (25) 88 (19) a8 patients randolnised but not treated, b2 lOgl0 drop or HCV RNA <600 IU/InL (quantitative) or <50 IU/InL (qualitative). *p < 0.0001 vs 180 gg/week ill overall pop.

Conclusion: Over the first 12 weeks of retreatment, Peg-IFNa-2a(40KD) (PEGASYS | plus ribavirin (COPEGUS | was effective in nonresponders to Peg-IFNa-2b (12KD)/ribavirin with cirrhosis/advanced fibrosis, with fixed induction doses (360 gg/week) being even more effective than standard doses (180 gg/week). Patients treated before the onset of advanced liver disease respond better to retreatment.

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EARLY DETECTION OF DEPRESSIVE SYMPTOMS DURING TREATMENT WITH PEGYLATED INTERFERON ~-2 A N D RIBAVIRIN IN EUTHYMIC CHRONIC HEPATITIS C PATIENTS

P.E. Golstein 1, P. Oswald2, J. Mendlewicz 2, J. Deviere 1, M. Adler 1.

1Department of Gastroenterology, Hdpital Eras'me, Universitd Libre de Bruxelles, Brussels', Belgium," 2Department of Psychiatry, H@ital Erasme, Universitd Libre de Bruxelles, Brussels, Belgium Background: Depressive symptoms are common during therapy of chronic hepatitis C (CHC) with pegylated interferon (PegIFN) and may compromise successful treatment. However, their systematic assessment has not been performed in euthymic patients with CHC. Aims: To prospectively assess the development of major depressive disorders (MDD) in adult naive euthymic CHC patients during combination therapy (PegIFN-~-2b 1.5 gg/kg/w and ribavirin 800 1200mg/d; 24 to 48 W) with validated Depression Rating Scales (DRS). Methods: Patient psychiatric history was firstly screened by the gastroenterologist according to the following criteria: hospitalization for psychiatric disease; suicidal attempt; substance abuse; dependence disorder; treatment with methadone, antidepressant drug or high dose of benzodiazepine. In the absence of all of these criteria, the psychiatrist evaluated each patient with the Mini-International Neuropsychiatric Interview (MINI), the Hamilton DRS-17 items (HAM-D(17)), the Montgomery Asberg DRS (MADRS), the Clinical Global Impressions and the Beck Depression Inventory (BDI). In the absence of psychiatric disorder according to the MINI, treatment of CHC was started. BDI was auto-performed every 2 W and psychiatric assessment was performed every 4W. Patients developing depressive symptoms (BDI/> 18 or HAM-D(17)/> 17) were reevaluated with the MINI to assess criteria for MDD. In case of MDD, escitalopram was started. Results: Of the 28 consecutive patients without psychiatric history screened by the gastroenterologist, 26 (93%) were free of active psychiatric disorder after psychiatric assessment and 19 were evaluable (9 males; 49.6• yrs). Mean baseline scores were low (• 2.4•

(HAM-D(17)); 2.4• (MADRS); 0.3• (CGI) and 2.3• (BDI). However, 5 patients (26%) developed MDD: 3 early episodes (from W6 to W 18) and 2 late episodes (at W42 and W48). Logistic regression analysis showed a trend for baseline HAM-D(17)/> 5 (p 0.06) or MADRS/> 5 (p 0.06) or BDI/> 6 (p 0.06) to predict early development of MDD during therapy. Conclusions: (1) There is a good correlation between the absence of psychiatric history screened by the gastroenterologist and the absence of psychiatric disorder assessed by the psychiatrist; (2) MDD develop in a high proportion of euthymic patients during therapy; (3) Baseline HAM-D(17)/> 5 or MADRS/> 5 or BDI/> 6 seem to predict early MDD but this trend needs to be confirmed by the ongoing study.

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LIVER STIFFNESS M E A S U R E M E N T (LSM) AS A TOOL TO MEASURE LIVER FIBROSIS IN TREATED PATIENTS WITH CHRONIC HEPATITIS C (CHC)

V. Grando-Lemaire 1 V. De L6dinghen2, V. Bourcier 1, N. Ganne-Carrie 1, J.C. Trinchet 1, M. Beaugrand 1. 1Hepatology Department, Jean Verdier

Hospital AP-HP, Bon@, France," 2Gas'troenterology and Hepatology Department, Haut-Ldvdque Hospital, Pessac, France Background and aims: Elastometry (Fibroscan| is a new non-invasive method to assess liver fibrosis. LSM is related to the amount of fibrotic tissue in the liver. Therefore, it could potentially demonstrate quantitative changes in liver fibrosis even when fibrosis stage remains unchanged. Methods: We studied LSM by Fibroscan| at the start and at the end of treatment in 85 patients with chronic hepatitis C (age: 48.8• 63 males, Metavir fibrosis stage: F2 21, F3 17, F4 47). Sixty-two patients had an additional measurement 6 months later. All patients were treated by peg-interferon and ribavirin at usual doses from 6 to 12 months according to genotype and/or virological response. Results: Mean LSM had decreased during treatment in the whole population: 17.4• 12 kPa before and 14.0• 11 kPa after treatment (p 0.0003). Among virological responders, 39/53 had decreased LSM at the end of treatment (74%). The mean value of LSM decreased 3.5 kPa. Among non responders, 17/32 had decreased LSM at the end of treatment (53.1%). The mean value of LSM decreased 0.8 kPa. Among the 62 patients evaluated 6 months after treatment, 29 were sustained responders, 7 relapsers and 23 non-responders. The variation of LSM from the end of treatment to 6 months after was 9.1 to 7.5kPa in sustained virological responders, 11.2 to 12.8 kPa in relapsers and 13.3 to 16.1 kPa in non-responders. Conclusion: LSM could be used to monitor liver fibrosis in treated patients with CHC. Results are compatible with a reduction of fibrosis during treatment in the whole population of treated patients but more pronounced in responders. In sustained virological responders, LSM further decrease after the end of treatment.

157~ UPTAKE OF HEPATITIS C VIRUS (HCV) TREATMENT A M O N G INJECTION DRUG USERS (IDUS) IN VANCOUVER, CANADA J. Grebely 1, B. Conway 1, J. Raffa 2 , C. Lai 3, M. Krajden4 , M.W. Tyndall 3.

1Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouve~ BC, Canada," 2Department of Statistics, University of British Columbia, Vancouve~ B C, Canada," 3BC Centre for Excellence in HIV/AIDS, Vancouveg BC, Canada," 4BC Centre for Disease Control, Vancouve~ BC, Canada Background and Aims: Although 70% of new HCV infections occur among injection drug users (IDUs), the majority are excluded from treatment despite the fact that treatment in this group has been shown to be safe and effective. This study sought to determine HCV treatment uptake in a large cohort of inner city IDUs.

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.

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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

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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.

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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.