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251. Mucosal-Associated Invariant T Cells Are More Activated in Chronic Hepatitis B, but Not Depleted in Blood: Reversal by Antiviral Therapy.

Author

Boeijen, Lauke L., Montanari, Noé R., de Groen, Rik A., van Oord, Gertine W., van der Heide-Mulder, Marieke, de Knegt, Robert J., and Boonstra, André

Subjects
CHRONIC hepatitis B, ANTIVIRAL agents, T cells, NUCLEOSIDE derivatives, IMMUNE response, PHYSIOLOGICAL effects of cytokines, BLOOD testing, THERAPEUTICS
Abstract

Background: Mucosal-associated invariant T (MAIT) cells might play a role in control of viral replication during chronic hepatitis B (cHBV) infection, but little is known of their number, phenotype, or function in cHBV patients.Methods: We performed flow cytometry on CD3+Vɑ7.2+CD161+ MAIT cells in blood of 55 cHBV patients. Nine patients were sampled before and on entecavir treatment. Six patients on therapy underwent a liver biopsy for flow cytometric analysis. Measurements included MAIT cell frequency, phenotype, and cytokine-producing capacity.Results: The MAIT cells were not deleted in blood or liver of cHBV patients compared with healthy controls, but they had higher percentages of CD38+ MAIT cells in blood, which declined on entecavir treatment. Peripheral MAIT cells of patients in the HBeAg-negative phase were least activated. Cytokine-producing MAIT cells were as frequent, but granzyme B-producing MAIT cells were more frequent upon stimulation with Escherichia coli compared with healthy controls.Conclusions: We demonstrate that, in sharp contrast to hepatitis C virus and human immunodeficiency virus patients, MAIT cells isolated from HBV patients are not deleted but are more activated, which can be normalized by nucleoside analog therapy. These observations may aid in deciphering the role of MAIT cells in immune responses to HBV. [ABSTRACT FROM AUTHOR]

Published
2017
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252. Durability of Response After Hepatitis B Surface Antigen Seroclearance During Nucleos(t)ide Analogue Treatment in a Multiethnic Cohort of Chronic Hepatitis B Patients: Results After Treatment Cessation.

Author

Heng Chi, Wong, David, Jie Peng, Jiawei Cao, Van Hees, Stijn, Vanwolleghem, Thomas, Xun Qi, Liang Chen, Feld, Jordan J., de Knegt, Robert J., Hansen, Bettina E., and Janssen, Harry L. A.

Subjects
CHRONIC hepatitis B, HEPATITIS B virus, CELL surface antigens, NUCLEOSIDES, DISEASE relapse, THERAPEUTICS
Abstract

In 70 chronic hepatitis B patients with hepatitis B surface antigen seroclearance during nucleos(t)ide analogue therapy, response was sustained in all 54 patients who discontinued treatment. Clinically significant relapses as indicated by high hepatitis B virus DNA and ALT levels were not observed. Anti-HBs positivity may not be required to ensure sustained off-treatment response. [ABSTRACT FROM AUTHOR]

Published
2017
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253. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON).

Author

Heng Chi, Hansen, Bettina E., Simin Guo, Ning Ping Zhang, Xun Qi, Liang Chen, Qing Guo, Arends, Pauline, Ji-Yao Wang, Verhey, Elke, de Knegt, Robert J., Qing Xie, Janssen, Harry L. A., Chi, Heng, Guo, Simin, Zhang, Ning Ping, Qi, Xun, Chen, Liang, Guo, Qing, and Wang, Ji-Yao

Subjects
CHRONIC hepatitis B, INTERFERONS, RANDOMIZED controlled trials, NUCLEOSIDES, ANTIGENS, THERAPEUTICS, ANTIVIRAL agents, COMBINATION drug therapy, COMPARATIVE studies, DNA, HEPATITIS viruses, RESEARCH methodology, MEDICAL cooperation, POLYETHYLENE glycol, PROTEINS, PURINES, RECOMBINANT proteins, RESEARCH, STATISTICAL sampling, VIRAL antigens, LOGISTIC regression analysis, EVALUATION research, TREATMENT effectiveness
Abstract

Background: We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t)ide analogue (NA) therapy, compared with continued NA monotherapy.Methods: This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for >12 months and had an HBV DNA load of <2000 IU/mL. Patients were randomly assigned in a 1:1 ratio to 48 weeks of peginterferon add-on therapy (n = 39) or continued NA monotherapy (n = 38). Response (defined as HBeAg seroconversion with an HBV DNA load of <200 IU/mL) was assessed at week 48, with responders discontinuing NA therapy at week 72.Results: The primary end point (response at week 96) was achieved in 18% of patients who were assigned peginterferon add-on therapy versus 8% of patients assigned NA monotherapy (P = .31). Among 58 interferon-naive patients, add-on therapy led to a greater frequency of HBeAg seroconversion (30% vs 7%; P = .034) and response (26% vs 7%; P = .068) at week 96, compared with monotherapy. Among 8 responders at week 48 who discontinued NA therapy at week 72, 6 patients (75%) maintained a response until week 96 (4 of 6 [67%] in the add-on therapy group vs 2 of 2 [100%] in the monotherapy group; P = 1.00). Adverse events were mainly related to peginterferon.Conclusion: The primary end point was negative, but peginterferon add-on therapy appeared to result in a greater frequency of HBeAg seroconversion, compared with NA monotherapy, in interferon-naive patients receiving NA therapy.Clinical Trials Registration: NCT01532843. [ABSTRACT FROM AUTHOR]

Published
2017
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258. Gene Expression Profiling To Predict and Assess the Consequences of Therapy-Induced Virus Eradication in Chronic Hepatitis C Virus Infection

Author

Hou, Jun, primary, van Oord, Gertine, additional, Groothuismink, Zwier M. A., additional, Claassen, Mark A. A., additional, Kreefft, Kim, additional, Zaaraoui-Boutahar, Fatiha, additional, van IJcken, Wilfred F. J., additional, Osterhaus, Albert D. M. E., additional, Janssen, Harry L. A., additional, Andeweg, Arno C., additional, de Knegt, Robert J., additional, and Boonstra, Andre, additional

Published
2014
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260. Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis

Author

Maan, Raoel, primary, van der Meer, Adriaan J., additional, Hansen, Bettina E., additional, Feld, Jordan J., additional, Wedemeyer, Heiner, additional, Dufour, Jean-François, additional, Zangneh, Hooman F., additional, Lammert, Frank, additional, Manns, Michael P., additional, Zeuzem, Stefan, additional, Janssen, Harry L.A., additional, de Knegt, Robert J., additional, and Veldt, Bart J., additional

Published
2014
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263. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians

Author

Arends, Pauline, primary, Sonneveld, Milan J, additional, Zoutendijk, Roeland, additional, Carey, Ivana, additional, Brown, Ashley, additional, Fasano, Massimo, additional, Mutimer, David, additional, Deterding, Katja, additional, Reijnders, Jurriën G P, additional, Oo, Ye, additional, Petersen, Jörg, additional, van Bömmel, Florian, additional, de Knegt, Robert J, additional, Santantonio, Teresa, additional, Berg, Thomas, additional, Welzel, Tania M, additional, Wedemeyer, Heiner, additional, Buti, Maria, additional, Pradat, Pierre, additional, Zoulim, Fabien, additional, Hansen, Bettina, additional, and Janssen, Harry L A, additional

Published
2014
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264. Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters

Author

van der Meer, Adriaan J, primary, Hansen, Bettina E, additional, Fattovich, Giovanna, additional, Feld, Jordan J, additional, Wedemeyer, Heiner, additional, Dufour, Jean-François, additional, Lammert, Frank, additional, Duarte-Rojo, Andres, additional, Manns, Michael P, additional, Ieluzzi, Donatella, additional, Zeuzem, Stefan, additional, Hofmann, W Peter, additional, de Knegt, Robert J, additional, Veldt, Bart J, additional, and Janssen, Harry L A, additional

Published
2014
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266. 1222ABT-450/r/Ombitasvir and Dasabuvir with Ribavirin Achieves High Sustained Virologic Response Rates Regardless of Baseline Characteristics: Pooled Analyses of the SAPPHIRE-I and SAPPHIRE-II Studies

Author

Feld, Jordan J., primary, Weiland, Ola, additional, Marinho, Rui Tato, additional, Wedemeyer, Heiner, additional, Jacobson, Ira M., additional, Jensen, Donald M., additional, Hassanein, Tarek, additional, De Ledinghen, Victor, additional, Diago, Moisés, additional, Magenta, Lorenzo, additional, De Knegt, Robert J., additional, Xiong, Junyuan J., additional, Coakley, Eoin, additional, Baykal, Tolga, additional, Tatsch, Fernando, additional, and Foster, Graham R., additional

Published
2014
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272. Immunological Analysis During Interferon-Free Therapy for Chronic Hepatitis C Virus Infection Reveals Modulation of the Natural Killer Cell Compartment.

Author

Spaan, Michelle, van Oord, Gertine, Kreefft, Kim, Hou, Jun, Hansen, Bettina E., Janssen, Harry L. A., de Knegt, Robert J., and Boonstra, Andre

Subjects
HEPATITIS C treatment, INTERFERONS, HEPATITIS C, KILLER cells, CYTOKINES, IMMUNOLOGY, ANTIVIRAL agents, T cells, IMIDAZOLES, ISOQUINOLINE, SULFONAMIDES, CELL receptors, COMPARATIVE studies, GENES, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RNA, VIRAL load, EVALUATION research, CASE-control method, CHRONIC hepatitis C, THERAPEUTICS, PHYSIOLOGY
Abstract

Background: Chronic hepatitis C virus (HCV) infection is a global health problem, resulting in liver failure, hepatocellular carcinoma, and liver-related death. Natural killer (NK) cells are innate immune cells, and their activity is known to correlate to viral treatment response of HCV. In this study, we investigate the immune effects of viral load decline with direct-acting antivirals (DAAs) in blood.Methods: Twelve patients with chronic HCV were treated with asunaprevir and daclatasvir, and peripheral blood was analyzed at various time points during therapy.Results: In line with previous studies, we confirmed restoration of HCV-specific T-cell frequency upon viral load decline. In addition, we show that serum interferon (IFN)-γ inducible-protein 10, interleukin (IL)-12p40, and IL-18 levels decreased early after start of therapy. Surface expression of activation receptors NKp30, NKp46, and inhibitory receptor NKG2A on blood NK cells reduced during therapy. In addition, the expression of TRAIL on NK cells was reduced during IFN-free therapy, suggesting a decrease in TRAIL-mediated killing by NK cells.Conclusions: We show that viral load decline as a consequence of treatment with novel DAAs in chronic HCV patients reduces serum levels of NK cell-stimulating cytokines and causes correction of the altered NK cell phenotype observed in chronic HCV patients.Clinical Trials Registration: NCT02282709. [ABSTRACT FROM AUTHOR]

Published
2016
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273. Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Author

Heerkens, Luc, van Kleef, Laurens A., de Knegt, Robert J., Voortman, Trudy, and Geleijnse, Johanna M.

Subjects
*FATTY liver, *MYOCARDIAL infarction, *NON-alcoholic fatty liver disease, *PATIENTS, *HYPERTENSION
Abstract

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60–80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002–2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48–84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality. [ABSTRACT FROM AUTHOR]

Published
2023
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277. Pharmacokinetics and Antiviral Activity of Phx1766, a Novel HCV Protease Inhibitor, Using An Accelerated Phase I Study Design

Author

Hotho, Daphne M, primary, de Bruijne, Joep, additional, O'Farrell, A Marie, additional, Boyea, Teresa, additional, Li, Jianke, additional, Bracken, Michele, additional, Li, Xin, additional, Campbell, David, additional, Guler, Hans-Peter, additional, Weegink, Christine J, additional, Schinkel, Janke, additional, Molenkamp, Richard, additional, van de Wetering de Rooij, Jeroen, additional, van Vliet, Andre, additional, Janssen, Harry LA, additional, de Knegt, Robert J, additional, and Reesink, Hendrik W, additional

Published
2012
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278. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study

Author

Razavi, Homie, Robbins, Sarah, Zeuzem, Stefan, Negro, Francesco, Buti, Maria, Duberg, Ann-Sofi, Roudot-Thoraval, Françoise, Craxi, Antonio, Manns, Michael, Marinho, Rui T, Hunyady, Bela, Colombo, Massimo, Aleman, Soo, Antonov, Krasimir, Arkkila, Perttu, Athanasakis, Kostas, Blach, Sarah, Blachier, Martin, Blasco, Antonio J, Calinas, Filipe, Calleja, Jose L, Christensen, Peer B, Cramp, Matthew E, Croes, Esther, de Knegt, Robert J, de Ledinghen, Victor, Delile, Jean-Michel, Estes, Chris, Falconer, Karolin, Färkkilä, Martti, Flisiak, Robert, Frankova, Sona, Gamkrelidze, Ivane, García-Samaniego, Javier, Genov, Jordan, Gerstoft, Jan, Gheorghe, Liana, Goldis, Adrian, Gountas, Ilias, Gregorčič, Sergeja, Gschwantler, Michael, Gunter, Jessie, Halota, Waldemar, Harcouet, Laura, Hézode, Christophe, Hoffmann, Patrick, Horvath, Gabor, Hrstic, Irena, Jarčuška, Peter, Jelev, Deian, Jeruma, Agita, Kåberg, Martin, Kieran, Jennifer, Kondili, Loreta A, Kotzev, Iskren, Krarup, Henrik, Kristian, Pavol, Lagging, Martin, Laleman, Wim, Lázaro, Pablo, Liakina, Valentina, Lukšić, Boris, Maimets, Matti, Makara, Mihály, Mateva, Lyudmila, Maticic, Mojca, Mennini, Francesco S, Mitova, Rumiana, Moreno, Christophe, Mossong, Joel, Murphy, Kimberly, Nde, Helen, Nemecek, Vratislav, Nonkovic, Dijana, Norris, Suzanne, Oltman, Marian, Øvrehus, Anne L H, Papatheodoridis, George, Pasini, Ken, Razavi-Shearer, Devin, Razavi-Shearer, Kathryn, Reesink, Henk W, Reic, Tatjana, Rozentale, Baiba, Ryder, Stephen D, Salupere, Riina, Sarmento-Castro, Rui, Sarrazin, Christoph, Schmelzer, Jonathan D, Schréter, Ivan, Seguin-Devaux, Carole, Simojoki, Kaarlo, Simonova, Marietta, Smit, Peter J, Souliotis, Kyriakos, Speiciene, Danute, Sperl, Jan, Stärkel, Peter, Struck, Daniel, Sypsa, Vana, Thornton, Lelia, Tolmane, Ieva, Tomasiewicz, Krzysztof, Valantinas, Jonas, Van Damme, Pierre, van de Vijver, David, van der Meer, Adriaan J, van Santen, Daniela, Van Vlierberghe, Hans, Vandijck, Dominique, Vella, Stefano, Videčnik-Zorman, Jerneja, Vogel, Wolfgang, Weis, Nina, and Hatzakis, Angelos

Abstract

Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination.

Published
2017
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279. Interferon-free antiviral therapy for chronic hepatitis C among patients in the liver transplant setting

Author

van Tilborg, Marjolein, Maan, Raoel, van der Meer, Adriaan J., and de Knegt, Robert J.

Abstract

Chronic hepatitis C (HCV) infection remains a major public health problem with many infected individuals worldwide. The revolutionary discovery of highly effective direct-acting antivirals (DAAs) makes chronic HCV infection a curable disease, even in patients with advanced liver disease. Liver function may improve shortly after initiation of antiviral therapy in patients on the waiting list and could even obviate the need for transplantation. However, whether these short term benefits also result in a favorable prognosis on the long-term remains to be seen and this fuels the discussion whether DAAs should be used prior to liver transplantation in all patients. Following liver transplantation, DAA treatment is also highly effective so that postponing antiviral treatment to the post-transplant setting may be better for certain patients. Furthermore, the discussion whether HCV positive organ donors should be used now viral eradication is achieved in almost all patients has regained interest.

Published
2017
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283. Potent Immune Activation in Chronic Hepatitis C Patients upon Administration of An Oral Inducer of Endogenous Interferons that Acts via Toll-Like Receptor 7

Author

Boonstra, Andre, primary, Liu, Bi-Sheng, additional, Groothuismink, Zwier MA, additional, Bergmann, Jilling F, additional, de Bruijne, Joep, additional, Hotho, Daphne M, additional, Hansen, Bettina E, additional, van Vliet, Andre A, additional, van de Wetering de Rooij, Jeroen, additional, Fletcher, Simon P, additional, Bauman, Lisa A, additional, Rahimy, Mohamad, additional, Appleman, James R, additional, Freddo, James L, additional, Reesink, Hendrik W, additional, de Knegt, Robert J, additional, and Janssen, Harry LA, additional

Published
2011
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286. Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon–ribavirin combination therapy after 4 weeks of treatment

Author

Orlent, Hans, primary, Desombere, Isabelle, additional, Hansen, Bettina, additional, Van Vlierberghe, Hans, additional, Haagmans, Bart, additional, De Knegt, Robert J., additional, Schalm, Solko W., additional, Leroux-Roels, Geert, additional, and Janssen, Harry L.A., additional

Published
2010
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292. Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor

Author

de Bruijne, Joep, primary, Bergmann, Jilling F, additional, Weegink, Christine J, additional, van Nieuwkerk, Carin MJ, additional, de Knegt, Robert J, additional, Komoda, Yasumasa, additional, van de Wetering de Rooij, Jeroen J, additional, van Vliet, Andre, additional, Jansen, Peter LM, additional, Molenkamp, Richard, additional, Schinkel, Janke, additional, Reesink, Hendrik, additional, and Janssen, Harry LA, additional

Published
2010
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293. S2069 Quantitative Measure of Liver Function Using 13C-Galactose (GBT) and 13C-Methacetin (MBT) Breath Tests and Hyaluronic Acid As Serum Markers in Patients with Chronic Hepatitis B or Chronic Hepatitis C

Author

Stibbe, Krista, primary, Verveer, Claudia, additional, Francke, Jan, additional, Hansen, Bettina E., additional, Zondervan, Pieter E., additional, Kuipers, Ernst J., additional, de Knegt, Robert J., additional, and van Vuuren, Anneke, additional

Published
2008
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294. Randomized placebo controlled phase I/II trial of α-galactosylceramide for the treatment of chronic hepatitis C

Author

Veldt, Bart J., primary, van der Vliet, Hans J.J., additional, von Blomberg, B. Mary E., additional, van Vlierberghe, Hans, additional, Gerken, Guido, additional, Nishi, Nobusuke, additional, Hayashi, Kunihiko, additional, Scheper, Rik J., additional, de Knegt, Robert J., additional, van den Eertwegh, Alfons J.M., additional, Janssen, Harry L.A., additional, and van Nieuwkerk, Carin M.J., additional

Published
2007
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295. ?-Glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-?-2b in chronic hepatitis C non-responders

Author

Bergmann, Jilling F., primary, Vrolijk, Jan M., additional, van der Schaar, Peter, additional, Vroom, Brigitte, additional, van Hoek, Bart, additional, van der Sluys Veer, Annet, additional, de Vries, Richard A., additional, Verhey, Elke, additional, Hansen, Bettina E., additional, Brouwer, Johannes T., additional, Janssen, Harry L. A., additional, Schalm, Solko W., additional, and de Knegt, Robert J., additional

Published
2007
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296. Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and Fibroscan�predicts the absence of significant liver fibrosis

Author

Berends, Maartje A. M., primary, Snoek, Josje, additional, de Jong, Elke M.G.J., additional, Van Krieken, J. Han, additional, de Knegt, Robert J., additional, van Oijen, Martijn G. H., additional, van de Kerkhof, Peter C. M., additional, and Drenth, Joost. P. H., additional

Published
2007
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297. Inosine triphosphate pyrophosphohydrolase activity: more accurate predictor for ribavirin-induced anemia in hepatitis C infected patients than ITPA genotype.

Author

Chantal Peltenburg, Nicole, Bakker, Jaap A., Vroemen, Wim H. M., de Knegt, Robert J., Leers, Mathie P. G., Bierau, Jörgen, and Verbon, Annelies

Subjects
GENETIC polymorphism research, RIBAVIRIN, HEPATITIS C, INOSINE, ANEMIA
Abstract

Background: ITPA polymorphisms have been associated with protection against ribavirin-induced anemia in chronic hepatitis C (HCV) patients. Here we determined the association of inosine triphosphate pyrophospho-hydrolase (inosine triphosphatase or ITPase) enzyme activity with ITPA genotype in predicting ribavirin-induced anemia. Methods: In a cohort of 106 HCV patients, hemoglobin (Hb) values were evaluated after 4 weeks (T4) and at the time of lowest Hb value (Tnadir). ITPase activity was measured and ITPA genotype determined. Single-nucleo-tide polymorphisms (SNPs) tested were C.124+21A>C and c.94C>A. ITPase activity ≥1.11 mU/mol Hb was considered as normal. Results: After 4 weeks of treatment, 78% of the patients with normal ITPase activity were anemic and 21% of the patients with low ITPase activity (p<0.001). Stratified by genotype, the percentages of anemic patients were: wt/wt 76%, wt/c.l24+21A>C 46% (p=0.068), and wt/c.94C>A 29% (p=0.021). At Tnadir, virtually all patients with normal ITPase activity were anemic, compared to only 64% of the patients with low activity (p=0.02). Thirteen patients had wt/c.l24+241A>C genotype. Within this group all five patients with normal ITPase activity and only four of eight with decreased activity developed anemia. Presence of HCV RNA did not influence ITPase activity. Conclusions: This study is the first to report that ITPase activity predicts the development of anemia during riba-virin treatment. ITPase activity and ITPA genotype have high positive predictive values for development of ribavirin-induced anemia at any time during treatment, but ITPase activity predicts ribavirin-induced anemia more accurately. [ABSTRACT FROM AUTHOR]

Published
2015
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298. The Intrahepatic T Cell Compartment Does Not Normalize Years After Therapy-Induced Hepatitis C Virus Eradication.

Author

Spaan, Michelle, Claassen, Mark A. A., Jun Hou, Janssen, Harry L. A., de Knegt, Robert J., and Boonstra, Andre

Subjects
HEPATITIS C, CELLULAR immunity, T cells, INTERLEUKIN-10, TRANSFORMING growth factors-beta, LIVER physiology, IMMUNOLOGY
Abstract

Little is known about the immune status in liver and blood of patients with chronic hepatitis C virus (HCV) infection long after therapy-induced viral clearance. In this study, we demonstrate that, 4 years after clearance, regulation of HCV-specific immunity in blood by regulatory T cells (Tregs) and the immunosuppressive cytokines interleukin 10 and transforming growth factor β is still ongoing. Importantly, analysis of liver specimens collected 4 years after HCV clearance shows that intrahepatic Tregs are still present in all patients, suggesting that liver T cells remain regulated. Identifying mechanisms that regulate HCV-specific memory T-cell responses after clearance is highly relevant for the development of protective vaccines, especially in patients at high risk of reinfection. [ABSTRACT FROM AUTHOR]

Published
2015
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