Gregory Thomas Everson

Effectiveness of Simeprevir Plus Sofosbuvir, with or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

BACKGROUND & AIMS The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. METHODS We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment--a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. RESULTS The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. CONCLUSIONS In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.

All‐oral direct‐acting antiviral therapy in HCV‐advanced liver disease is effective in real‐world practice: observations through HCV‐TARGET database

Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV‐TARGET collects data in patients treated at tertiary academic and community centres.

Treatment of chronic hepatitis C with protease inhibitor‐based therapy after liver transplantation

Clinical perspectives in hepatology aims to engage two experts with opinions supporting differing perspectives on the management of a case. Typically, the case represents an area of debate or evolving practice in clinical hepatology. The case described by Dr. Reddy provides an opportunity to discuss the benefits and risks of using a direct-acting antiviral as part of a treatment regimen for aggressive post–liver transplant (LT) hepatitis C.

HCV Council--critical appraisal of data: recommendations for clinical practice in a rapidly evolving therapeutic landscape.

HCV Council 2014, like its predecessor HCV Council 2011, assembled leading clinicians and researchers in the field of hepatitis C to critically evaluate current data regarding best practices for managing patients with chronic hepatitis C virus (HCV).

277 GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN IMPROVES BIOPSY NECRO-INFLAMMATORY SCORES AND ALT NORMALIZATION AT 48 WEEKS VERSUS PEG-IFN/RIBAVIRIN IN GENOTYPE 1 CHRONIC HCV PATIENTS

276 WEEK 4 HCVRNA IS THE OPTIMAL PREDICTOR OF SVR IN BOTH HIV POSITIVE AND NEGATIVE SUBJECTS WITHIN THE AUSTRALIAN TRIAL IN ACUTE HCV G.V. Matthews, J. Grebely, M. Hellard, B. Yeung, P. Marks, W. Rawlinson, J. Kaldor, G.J. Dore, ATAHC Study Group. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales, Sydney, NSW, Burnet Institute, Melbourne, VIC, Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, NSW, Australia E-mail: gmatthews@nchecr.unsw.edu.au

1181 PHARMACOGENOMIC ANALYSIS REVEALS IMPROVED VIROLOGIC RESPONSE IN ALL IL-28B GENOTYPES IN NAIVE GENOTYPE 1 CHRONIC HCV PATIENTS TREATED WITH GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN

1181 PHARMACOGENOMIC ANALYSIS REVEALS IMPROVED VIROLOGIC RESPONSE IN ALL IL-28B GENOTYPES IN NAIVE GENOTYPE 1 CHRONIC HCV PATIENTS TREATED WITH GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN J.G. McHutchison, A.J. Thompson, I.M. Jacobson, T.D. Boyer, E.R. Schiff, G.T. Everson, J.M. Vierling, M.L. Shiffman, R.S. Brown, A.M. Di Bisceglie, S.C. Gordon, W.M. Lee, Z. Guo, T.H. King, B. Armstrong, T.C. Rodell, D. Apelian. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, Center for Liver Diseases, University of Miami School of Medicine, Miami, FL, Department of Medicine, University of Colorado Denver, Aurora, CO, Department of Medicine and Surgery, Baylor College of Medicine, St. Luke’s Episcopal Hospital, Houston, TX, Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, Columbia University College of Physicians & Surgeons, New York, NY, Saint Louis University, St. Louis, MO, Henry Ford Hospital, Detroit, MI, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, GlobeImmune, Inc., Louisville, CO, QST Consultations, LTD, Allendale, MI, USA E-mail: mchut001@mc.duke.edu