1192 THE BURDEN OF VIRAL HEPATITIS C IN EUROPE: A PROPENSITY ANALYSIS OF PATIENT OUTCOMES

POSTERS 1192 THE BURDEN OF VIRAL HEPATITIS C IN EUROPE: A PROPENSITY ANALYSIS OF PATIENT OUTCOMES M. Di Bonaventura1 , Y. Yuan2 , J.-S. Wagner1 , G. L’Italien2,3 , P. Mc Ewan4 , P. Langley5 . 1 Health Sciences Practice, Kantar Health, New York, NY, 2 Global Health Outcomes, Bristol-Myers Squibb, Princeton, NJ, 3 Yale University School of Medicine, New Haven, CT, USA; 4 School of Human and Health Services, Swansea University, Swansea, UK; 5 College of Pharmacy, University of Minnesota, Minneapolis, MN, USA E-mail: [email protected] Background: Viral hepatitis C (HCV) affects 170 million patients worldwide with prevalence rates estimated at 1 percent across Europe. The objective of the current study is to examine the burden of HCV in EU from a patient perspective. Methods: Using data from the 2010 EU National Health and Wellness Survey (which included UK, France, Germany, Italy, and Spain), patients who reported a HCV diagnosis (n = 333) were compared to a propensity-score-matched non-HCV control group (n = 333) on measures of quality of life (using the SF-12v2), work productivity (WPAI questionnaire), and healthcare resource use in the past six months. All analyses applied sampling weights to project to the respective country population. Results: Prior to matching, HCV patients reported significantly lower levels of mental component summary (MCS) scores (43.8 vs. 46.8) and physical component summary (PCS) scores (42.8 vs. 48.0; p’s <0.05) and higher levels of absenteeism (8.1% vs. 5.3%), presenteeism (27.8% vs. 16.2%), overall work impairment (32.2% vs. 19.6%), activity impairment (34.5% vs. 25.2%), ER visits (0.41 vs. 0.21), hospitalizations (0.27 vs. 0.14), and physician visits (9.9 vs. 5.5; all p’s <0.05). The propensity-matching process eliminated differences between the two groups on gender, age, ethnicity, income, employment status, insurance, smoking behavior, alcohol use, exercise behavior, anxiety, depression, hepatitis B, and HIV/AIDS. Although HCV patients were no different than matched controls on quality of life measures, HCV patients did report significantly higher rates of presenteeism (27.7% vs. 20.4%, p < 0.05), overall work impairment (31.6% vs. 24.7%, p < 0.05), and marginally more physician visits (9.8 vs. 8.2, p = 0.05) than matched controls. Conclusions: These results are similar to previous studies conducted using the US and Japan NHWS databases. The results suggest that HCV can be a substantial burden on patients in terms of work productivity loss and additional physician visits. Consequently, HCV is likely associated with greater economic costs, though future research is necessary to examine these links. 1193 ANTIGEN PROCESSING AND PROTEASOME DEGRADATION PATHWAYS ARE INVOLVED IN PATIENTS WITH CHRONIC HEPATITIS C WITH NEGATIVE PREDICTORS OF RESPONSE TO PEGYLATED INTERFERON AND RIBAVIRIN (PEG-IFN/RBV) A. Birerdinc1,2 , A. Afendy1,3 , M. Stepanova1,3 , I. Younossi1 , G. Manyam1,2 , A. Baranova1,2 , Z. Younossi1,3 . 1 Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, 2 Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, 3 Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA E-mail: [email protected] Background: Treatment of CH-C patients with PEG-IFN/RBV results in 50–55% SVR. These rates are lower in African Americans (AA), obese and those without early virologic response (EVR). Thissuggest sinnate differences in host immune and inflammatory profile of different cohorts, affecting SVR. Aims: Asses the status of functional pathways based on differential gene expression in pre-treatment peripheral blood mononuclear cells (PBMC) of CH-C patients with negative predictors of response.

Methods: CH-C patients undergoing treatment with PEG-IFN/RBV were included. Pre-treatment blood samples were collected into PAXgene™ RNA tubes. Patients received a full course of PEGIFN/RBV with 41% SVR. From the pre-treatment PBMCs, total RNA was extracted, quantified and used for one step RT-PCR to profile 160 mRNAs. Expression levels of mRNAs were normalized with “housekeeping” genes. Differentially expressed genes were separated into up and down-regulated gene lists according to the presence or absence of a “negative predictor of response” and subjected to KEGG Pathway Painter that allows high-throughput visualization of pathway-specific changes in expression profiles. Genes were consolidated into networks associated with each predictor of response. Results: Sixty-seven CH-C patients had complete clinical and gene expression data. Pre-treatment gene expression data showed differential expression of 46 genes associated with AA race, 34 genes with obesity, and 18 genes with lack of EVR. Pathway analysis shows that genes associated with the core components of the antigen processing and presentation and proteasome pathways (PSMB8, PSMB9, PSME1 and PSME2) were differentially expressed in AA, obese and non-EVR patients. Proteasome is involved in the regulation of essential cellular processes such as transcription, cell cycle progression, differentiation, apoptosis and control of inflammatory and immune responses. Specifically, PSMB8 is a major component of interferon gamma-induced response of the immune system, suggesting that innate differences in host proteasome may play a role in SVR. Conclusions: Pathway-centered analysis of pre-treatment gene expression from CH-C patients suggests that Antigen Processing and Presentation and Proteasome Pathways may be associated with negative predictors of response to PEG-IFN/RBV (AA, obese or those without EVR). Further studies of these pathways may delineate a link between host immune response and lack of achieving SVR.

08d: VIRAL HEPATITIS C: CLINICAL (NEW COMPOUNDS, RESISTANCE)

1194 SUSTAINED VIROLOGIC RESPONSE AND BOCEPREVIR RESISTANCE-ASSOCIATED VARIANTS OBSERVED IN PATIENTS INFECTED WITH HCV GENOTPYPE 1A/1B WHEN TREATED WITH BOCEPREVIR PLUS PEGINTERFERON ALFA-2B/RIBAVIRIN C. Brass1 , R.J.O. Barnard2 , J.A. Howe1 , R.A. Ogert1 , R. Ralston1 , N. Boparai1 , M. Burroughs1 , V. Sniukiene1 , P. Mendez1 , J. Albrecht1 . 1 Merck and Co Inc, Kenilworth, NJ, 2 Merck and Co Inc, North Wales, PA, USA E-mail: [email protected] Background and Aims: The HCV-NS3 protease inhibitor boceprevir (BOC) combined with peginterferon alfa-2b plus ribavirin (PR) is effective for treatment of HCV genotype 1 infection. We assessed the SVR and BOC resistance associated variants (RAVs) in patients who did not achieve SVR by genotype 1 subtype, G1a and G1b. Methods: 1500 patients (1097 treatment-naive; 403 treatmentfailure) were randomized to 4 weeks PR, followed by 1. PR plus placebo for 44 weeks (48 P/R), 2. PR plus response guided therapy (BOC RGT) treatment-naive (SPRINT-2): for 24 weeks, with additional 20 weeks P/R if detectable HCV-RNA during Weeks 8–24 (Week 24 stopping rule – all arms); treatment-failure (RESPOND-2): for 32 weeks, with additional 12 weeks PR if detectable HCV-RNA at Week 8 (Week 12 stopping rule – all arms), or

Journal of Hepatology 2011 vol. 54 | S363–S534

S471