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Mark S Sulkowski - One of the best experts on this subject based on the ideXlab platform.
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late relapse versus hepatitis c virus reinfection in patients with Sustained Virologic Response after sofosbuvir based therapies
Clinical Infectious Diseases, 2017Co-Authors: Christoph Sarrazin, V A Isakov, Evguenia S Svarovskaia, Charlotte Hedskog, Ross Martin, Krishna Chodavarapu, Diana M Brainard, Michael D Miller, Jeanmichel Molina, Mark S SulkowskiAbstract:Background The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish Virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment. Methods We investigated the prevalence of late recurrent viremia (patients with Sustained Virologic Response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish Virologic relapse from reinfection. Results Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following Sustained Virologic Response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had Virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment. Conclusions The incidence of late recurrent viremia was low. Distinguishing reinfection from Virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.
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1421 high Sustained Virologic Response rate in treatment naive hcv genotype 1a and 1b patients treated for 12 weeks with an interferon free all oral quad regimen interim results
Journal of Hepatology, 2012Co-Authors: Mark S Sulkowski, Diana M Brainard, M Rodrigueztorres, Eric Lawitz, M L Shiffman, Robert Herring, John G Mchutchison, P S Pang, David L Wyles, Francois HabersetzerAbstract:1421 HIGH Sustained Virologic Response RATE IN TREATMENT-NAIVE HCV GENOTYPE 1A AND 1B PATIENTS TREATED FOR 12 WEEKS WITH AN INTERFERON-FREE ALL-ORAL QUAD REGIMEN: INTERIM RESULTS M. Sulkowski, M. Rodriguez-Torres, E. Lawitz, M. Shiffman, S. Pol, R. Herring, J. McHutchison, P. Pang, D. Brainard, D. Wyles, F. Habersetzer. Johns Hopkins University School of Medicine, Lutherville, MD, Fundacion de Investigacion de Diego, Santurce, PR, Alamo Medical Research, San Antonio, TX, Liver Institute of Virginia, Richmond, VA, USA; Hopital Necker, Paris, France; Nashville Gastrointestinal Specialists, Inc., Nashville, TN, Gilead Sciences, Inc., Foster City, University of California, San Diego, La Jolla, CA, USA; Hopitaux Universitaires de Strasbourg, Strasbourg, France E-mail: msulkowski@jhmi.edu
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66 silen c2 Sustained Virologic Response svr and safety of bi201335 combined with peginterferon alfa 2a and ribavirin p r in chronic hcv genotype 1 patients with non Response to p r
Journal of Hepatology, 2011Co-Authors: Mark S Sulkowski, M Bourliere, J P Bronowicki, Anca Streinucercel, L Preotescu, T Asselah, J M Pawlotsky, Stephen D Shafran, Stanislas Pol, F A CaruntuAbstract:66 SILEN-C2: Sustained Virologic Response (SVR) AND SAFETY OF BI201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (P/R) IN CHRONIC HCV GENOTYPE-1 PATIENTS WITH NON-Response TO P/R M.S. Sulkowski, M. Bourliere, J.-P. Bronowicki, A. Streinu-Cercel, L. Preotescu, T. Asselah, J.-M. Pawlotsky, S. Shafran, S. Pol, F.A. Caruntu, S. Mauss, D. Larrey, C. Hafner, Y. Datsenko, J.O. Stern, R. Kubiak, W. Bocher, G. Steinmann. Johns Hopkins University, Baltimore, MD, USA; Hopital Saint Joseph, Marseille, Hopital de Brabois, Vandoeuvre Cedex, France; “Prof. Dr. Matei Bals” Institute of Infectious Diseases, Bucharest, Romania; Hopital Beaujon, Clichy Cedex, Hopital Henri Mondor, Creteil, France; University of Alberta, Edmonton, AB, Canada; Hopital Cochin, Paris, France; Center for HIV and Hepatogastroenterology, Dusseldorf, Germany; Hopital Saint-Eloi, Montpellier Cedex, France; Boehringer Ingelheim Pharma, Biberach, Germany; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA E-mail: msulkowski@jhmi.edu
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Ira M Jacobson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Rafael EstebanAbstract:Background & Aims We recently identified a polymorphism upstream of interleukin ( IL ) -28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. Methods HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P P P IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1–6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P Conclusions In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Dongliang Ge, Ira M JacobsonAbstract:BACKGROUND & AIMS: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. METHODS: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). RESULTS: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early Virologic Response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). CONCLUSIONS: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
Ira M Jacobson - One of the best experts on this subject based on the ideXlab platform.
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american gastroenterological association institute clinical practice update expert review care of patients who have achieved a Sustained Virologic Response after antiviral therapy for chronic hepatitis c infection
Gastroenterology, 2017Co-Authors: Ira M Jacobson, Joseph K Lim, Michael W. FriedAbstract:Chronic hepatitis C virus infection is well-recognized as a common blood-borne infection with global public health impact affecting 3 to 5 million persons in the United States and more than 170 million persons worldwide. Chronic hepatitis C virus infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma. Current therapies with all-oral direct-acting antiviral agents are associated with high rates of Sustained Virologic Response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, hepatocellular carcinoma, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored vs discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic hepatitis C virus who have achieved SVR.
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simeprevir increases rate of Sustained Virologic Response among treatment experienced patients with hcv genotype 1 infection a phase iib trial
Gastroenterology, 2014Co-Authors: S Zeuzem, Graham R. Foster, Michael W. Fried, Christophe Hézode, Ira M Jacobson, Thomas Berg, Edward Gane, P Ferenci, Gideon M Hirschfield, I V NikitinAbstract:Background & Aims Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV. Methods We analyzed data from patients who did not respond (null Response), had a partial Response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with Sustained Virologic Response (SVR; undetectable HCV RNA) at that time point. Results Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%−80% vs 23%; P Conclusions In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Ira M Jacobson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Rafael EstebanAbstract:Background & Aims We recently identified a polymorphism upstream of interleukin ( IL ) -28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. Methods HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P P P IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1–6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P Conclusions In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Dongliang Ge, Ira M JacobsonAbstract:BACKGROUND & AIMS: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. METHODS: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). RESULTS: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early Virologic Response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). CONCLUSIONS: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
Andrew J Muir - One of the best experts on this subject based on the ideXlab platform.
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long term patient centered outcomes in cirrhotic patients with chronic hepatitis c after achieving Sustained Virologic Response
Clinical Gastroenterology and Hepatology, 2021Co-Authors: Stefan Zeuzem, Andrew J Muir, Rafael Esteban, Zobair M Younossi, Andrei Racila, Marc Bourliere, Alessandra Mangia, Massimo ColomboAbstract:Background & Aims Achieving Sustained Virologic Response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis. Methods Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry ( clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV. Results Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p Conclusions Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.
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Sustained Virologic Response rates with telaprevir based therapy in treatment naive patients evaluated by race or ethnicity
Journal of Clinical Gastroenterology, 2015Co-Authors: Steven L Flamm, Michael W. Fried, Rajender K Reddy, Andrew J Muir, David R Nelson, Natalie Bzowej, James C Sullivan, Leif Bengtsson, Ralph Demasi, Christopher I WrightAbstract:Background The phase 3 studies of telaprevir (T) in combination with peginterferon α-2a and ribavirin (PR) in treatment-naive genotype 1 chronic hepatitis C virus-infected patients (ADVANCE/ILLUMINATE) were not designed a priori to assess the effect of race and ethnicity on treatment Response. However, these factors are important given the lower Sustained Virologic Response (SVR) rates observed in black and Hispanic/Latino patients treated with PR. Goals This retrospective pooled analysis evaluated the effect of race or ethnicity on treatment-naive patient Response to telaprevir-based therapy and assessed resistant variant profiles. Materials and methods This analysis comprised patients enrolled in ADVANCE (N=363) and ILLUMINATE (N=540) who received 12 weeks of telaprevir in combination with PR followed by 12 or 36 weeks of PR alone and patients in ADVANCE (N=361) who received 48 weeks of PR alone. Race and ethnicity were self-reported and not mutually exclusive. Results Higher SVR rates were observed with telaprevir-based therapy compared with PR in blacks [n=99 (62%) vs. n=28 (29%), respectively] and in Hispanics/Latinos [n=89 (72%) vs. n=38 (39%)]. The SVR was lower in telaprevir-treated blacks [n=99 (62%)] compared with nonblacks [n=791 (78%)] and in Hispanic/Latinos compared with non-Hispanics/Latinos [n=89 (72%) vs. n=801 (76%)]. Low discontinuation rates due to adverse events, including rash and anemia, were observed across subgroups. Resistance profiles were similar among the subgroups. Conclusions Treatment-naive black and Hispanic/Latino patients with genotype 1 chronic hepatitis C virus infection may benefit from telaprevir-based therapy, an important finding given the lower SVR rates observed in these patients when they are treated with PR alone.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Ira M Jacobson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Rafael EstebanAbstract:Background & Aims We recently identified a polymorphism upstream of interleukin ( IL ) -28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. Methods HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P P P IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1–6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P Conclusions In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Dongliang Ge, Ira M JacobsonAbstract:BACKGROUND & AIMS: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. METHODS: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). RESULTS: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early Virologic Response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). CONCLUSIONS: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
Stefan Zeuzem - One of the best experts on this subject based on the ideXlab platform.
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long term patient centered outcomes in cirrhotic patients with chronic hepatitis c after achieving Sustained Virologic Response
Clinical Gastroenterology and Hepatology, 2021Co-Authors: Stefan Zeuzem, Andrew J Muir, Rafael Esteban, Zobair M Younossi, Andrei Racila, Marc Bourliere, Alessandra Mangia, Massimo ColomboAbstract:Background & Aims Achieving Sustained Virologic Response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis. Methods Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry ( clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV. Results Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p Conclusions Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.
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serum sphingolipids predict de novo hepatocellular carcinoma in hepatitis c cirrhotic patients with Sustained Virologic Response
Liver International, 2019Co-Authors: Victoria T Mucke, Stefan Zeuzem, J Vermehren, Christoph Sarrazin, Dominique Thomas, Marcus M Mucke, Oliver Waidmann, Josef Pfeilschifter, Fabian Finkelmeier, Georgios GrammatikosAbstract:Background & aims Curing hepatitis C virus (HCV) infection reduces the risk of hepatocellular carcinoma (HCC) development, yet HCC occurs despite Sustained Virologic Response (SVR) in 2%-8% of cirrhotic patients. Sphingolipids (SLs) have been identified as new biomarkers of chronic liver disease and HCC. The aim of this study was to evaluate serum SLs as diagnostic HCC biomarkers in patients with HCV-associated cirrhosis at SVR12. Methods From 2014 to 2016, 166 patients with HCV-cirrhosis and SVR were recruited and SL profiles were measured at baseline and 12 weeks after completion of direct-acting antiviral (DAA) therapy. All patients received HCC surveillance in line with current guideline recommendations. Minimum follow-up period comprised 6 months. Results Our study included 130 (78%) patients without history of HCC, 25 (15%) with history of HCC prior DAA therapy and 11 (7%) patients with de novo HCC after FU12. In those with upcoming de novo HCC serum C24DHC (P = 0.006), C24:1DHC (P = 0.048) and C16Cer (P = 0.011) were significantly upregulated at FU12, but not AFP (P = 0.138). Contemporaneous ultrasound did not visualize HCC, at this time. C16Cer stayed sole independent predictor with high diagnostic accuracy of AFP-positive (AUC = 0.741) and -negative (AUC = 0.766) HCC development. Serum SL parameters decreased from baseline to SVR12. Conclusions C24DHC, C24:1DHC and especially C16Cer were superior to AFP in early detection of AFP-positive and -negative de novo HCC development. We observed significant SL profile changes upon SVR. SLs may play a role in non-invasive HCC surveillance and hepatocarcinogenesis.
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Sustained Virologic Response rates with telaprevir by Response after 4 weeks of lead in therapy in patients with prior treatment failure
Journal of Hepatology, 2013Co-Authors: Graham R. Foster, Pietro Andreone, Stefan Zeuzem, Zobair M Younossi, Paul J Pockros, Eric Lawitz, Stanislas Pol, Moises Diago, Stuart K Roberts, I LonjondomanecAbstract:Background & Aims For hepatitis C virus (HCV)-infected patients who have not responded to previous PegIFN/ribavirin treatment, it is unclear whether subsequent direct-acting antiviral therapy outcomes are better predicted by prior treatment Response or by on-treatment Response to a PegIFN/ribavirin lead-in. Methods In REALIZE, treatment-experienced patients randomized to the lead-in telaprevir arm received 4weeks of PegIFN-α-2a (180μg/week) and ribavirin (1000–1200mg/day), then 12weeks of telaprevir (750mg every 8h) plus PegIFN-α-2a/ribavirin, followed by 32weeks of PegIFN-α-2a/ribavirin. This subanalysis only included patients in the lead-in telaprevir arm with available week 4 on-treatment Response data ( n =240). Results After 4weeks of PegIFN/ribavirin, 90% of relapsers, 60% of partial responders, and 41% of null responders in the lead-in telaprevir arm had ⩾1log 10 HCV RNA reduction. Sustained Virologic Response (SVR) rates for telaprevir-treated patients with ⩾1 versus 10 HCV RNA reduction after the PegIFN/ribavirin lead-in were 94% versus 62% in relapsers, 59% versus 56% in partial responders and 54% versus 15% in null responders. Conclusions In prior relapsers and partial responders there is no apparent benefit of assessing Response after a PegIFN/ribavirin lead-in with the aim of guiding telaprevir-based treatment. For patients known to be prior null responders, on-treatment Response after a 4-week PegIFN/ribavirin lead-in may provide clinically useful prognostic information. However, withholding telaprevir-containing therapy in uncategorised treatment-experienced patient populations (i.e., that could include prior relapsers or partial responders), using Response after a PegIFN/ribavirin lead-in could potentially exclude some patients with a high chance of SVR.
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a Sustained Virologic Response is durable in patients with chronic hepatitis c treated with peginterferon alfa 2a and ribavirin
Gastroenterology, 2010Co-Authors: Mark G Swain, Stefan Zeuzem, Mitchell L Shiffman, Ming Yang Lai, Graham W E Cooksley, Douglas T Dieterich, Armand Abergel, Mario G Pessoa, Amy Lin, Andreas TietzAbstract:Background & Aims A Sustained Virologic Response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. Methods The durability of treatment Responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA ( Results Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1–2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. Conclusions In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.
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Sustained Virologic Response and clinical outcomes in patients with chronic hepatitis c and advanced fibrosis
Annals of Internal Medicine, 2007Co-Authors: Bart J Veldt, Stefan Zeuzem, Jenny E Heathcote, Heiner Wedemeyer, Juerg Reichen, Peter W Hofmann, Michael P Manns, Bettina E Hansen, Solko W Schalm, Harry L A JanssenAbstract:BACKGROUND: Clinical outcomes of chronic hepatitis C infection in patients with advanced fibrosis include liver failure, hepatocellular carcinoma, and death. OBJECTIVE: To investigate whether Sustained Virologic Response to treatment for hepatitis C is associated with improved clinical outcomes. DESIGN: Retrospective cohort study. SETTING: 5 hepatology units of tertiary care centers in Europe and Canada caring for patients with chronic hepatitis C treated between 1990 and 2003. PATIENTS: Consecutively treated patients with chronic hepatitis C who had biopsy-proven advanced fibrosis or cirrhosis (Ishak score, 4 to 6). MEASUREMENTS: Sustained Virologic Response, defined as absence of detectable hepatitis C virus RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non-liver-related), liver failure, and hepatocellular carcinoma. RESULTS: Of 479 patients, 29.6% had Sustained Virologic Response and 70.3% did not. Median follow-up was 2.1 years (interquartile range, 0.8 to 4.9 years). Four patients with and 83 without Sustained Virologic Response had at least 1 outcome event. Sustained Virologic Response was associated with a statistically significant reduction in the hazard of events (adjusted hazard ratio, 0.21 [95% CI, 0.07 to 0.58]; P = 0.003). The effect was largely attributable to a reduction in liver failure, which developed in no patients with and 42 patients without Sustained Virologic Response (5-year occurrence, 0% vs. 13.3% [CI, 8.4% to 18.2%]; unadjusted hazard ratio, 0.03 [CI, 0.00 to 0.91]). LIMITATIONS: Because few events occurred in the Sustained Virologic Response group, the study had limited ability to detect differences between groups in individual outcomes. In addition, the study was retrospective; selection and survival biases may therefore influence estimates of effect. CONCLUSION: Sustained Virologic Response to treatment is associated with improved clinical outcomes, mainly prevention of liver failure, in patients with chronic hepatitis C and advanced fibrosis.
Rafael Esteban - One of the best experts on this subject based on the ideXlab platform.
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long term patient centered outcomes in cirrhotic patients with chronic hepatitis c after achieving Sustained Virologic Response
Clinical Gastroenterology and Hepatology, 2021Co-Authors: Stefan Zeuzem, Andrew J Muir, Rafael Esteban, Zobair M Younossi, Andrei Racila, Marc Bourliere, Alessandra Mangia, Massimo ColomboAbstract:Background & Aims Achieving Sustained Virologic Response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis. Methods Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry ( clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV. Results Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p Conclusions Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.
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interleukin 28b polymorphism improves viral kinetics and is the strongest pretreatment predictor of Sustained Virologic Response in genotype 1 hepatitis c virus
Gastroenterology, 2010Co-Authors: Alexander J Thompson, Ira M Jacobson, Mark S Sulkowski, Andrew J Muir, Jacques Fellay, Kevin V Shianna, Thomas J Urban, Nezam H Afdhal, Rafael EstebanAbstract:Background & Aims We recently identified a polymorphism upstream of interleukin ( IL ) -28B to be associated with a 2-fold difference in Sustained Virologic Response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment Virologic Response and SVR. Methods HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid Virologic Response (RVR, week 4), complete early Virologic Response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P P P IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1–6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P Conclusions In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and Sustained Virologic Response and effectively predicts treatment outcome.
