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Article ; Online: Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals.

Casas-Deza, Diego / Espina, Silvia / Martínez-Sapiña, Ana / Del Moral-Bergos, Raquel / Garcia-Sobreviela, Maria Pilar / Lopez-Yus, Marta / Calmarza, Pilar / Bernal-Monterde, Vanesa / Arbones-Mainar, Jose M

Atherosclerosis

2023 Volume 375, Page(s) 59–66

Abstract: Background & aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardiovascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV, with positive ... ...

Abstract	Background & aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardiovascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy. Methods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR). Results: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (-22%) and HDL-TG (-18%) after one-year follow-up. Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this association. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evolution of glucose tolerance and IR after HCV eradication.
MeSH term(s)	Humans ; Insulin Resistance ; Antiviral Agents/therapeutic use ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Prospective Studies ; Lipoproteins ; Triglycerides ; Cholesterol ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepacivirus/genetics
Chemical Substances	Antiviral Agents ; Lipoproteins ; Triglycerides ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-05-17
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2023.05.003
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Article: Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease.

Casas-Deza, Diego / Martínez-Sapiña, Ana / Espina, Silvia / Garcia-Rodriguez, Beatriz / Fernandez-Bonilla, Eva M / Sanz-Paris, Alejandro / Gonzalez-Irazabal, Yolanda / Bernal-Monterde, Vanesa / Arbones-Mainar, Jose M

Journal of clinical medicine

2022 Volume 11, Issue 14

Abstract: Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes.: Objective!# ...

Abstract	Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.
Language	English
Publishing date	2022-07-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11144049
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Article ; Online: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) proteomic profiling of cerebrospinal fluid in the diagnosis of enteroviral meningitis: a proof-of-principle study.

Torres, Ignacio / Giménez, Estela / Vinuesa, Víctor / Pascual, Tania / Moya, Juan Miguel / Alberola, Juan / Martínez-Sapiña, Ana / Navarro, David

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

2018 Volume 37, Issue 12, Page(s) 2331–2339

Abstract: The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for diagnosing viral infections by directly testing clinical specimens has not previously been explored. In this proof-of-principle study, we tested ... ...

Abstract	The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for diagnosing viral infections by directly testing clinical specimens has not previously been explored. In this proof-of-principle study, we tested the hypothesis that proteomic profiling of cerebrospinal fluid (CSF) by mass spectrometry may be useful in the diagnosis of enteroviral (EV) meningitis. A total of 114 cryopreserved CSF samples were analyzed, of which 47 were positive for EV and 67 were negative. Total CSF proteins were precipitated and subjected to MALDI-TOF-MS analysis in a low (2-20 kDa) molecular weight range using a MicroFlex LT mass spectrometer. The whole data set was randomly split into a training set (n = 76 specimens) and a validation set (n = 38 samples). Backward/forward stepwise logistic regression analyses identified 30 peaks that were differentially present in EV-positive and EV-negative specimens. These were used to build a model which displayed an overall classification accuracy of 93%. The discriminative ability of the model was confirmed by using a validation sample set (overall accuracy 83%). In fact, the model was able to correctly classify 61 out of 67 EV-negative samples and 42 out of 47 EV-positive specimens. EV meningitis is associated with a distinctive protein profile that may be directly detectable in CSF specimens by MALDI-TOF-MS.
MeSH term(s)	Adolescent ; Cryopreservation ; Enterovirus Infections/cerebrospinal fluid ; Enterovirus Infections/diagnosis ; Female ; Gene Expression Profiling ; Humans ; Logistic Models ; Male ; Meningitis, Viral/cerebrospinal fluid ; Meningitis, Viral/diagnosis ; Proof of Concept Study ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult
Language	English
Publishing date	2018-09-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	603155-9
ISSN	1435-4373 ; 0934-9723 ; 0722-2211
ISSN (online)	1435-4373
ISSN	0934-9723 ; 0722-2211
DOI	10.1007/s10096-018-3380-x
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Article ; Online: Discrepancies in the detection of SARS-CoV-2 by qRT-PCR are dependent on the target gene used for its amplification: Implications in the diagnosis of clinical infection

Campos Pardos, Elena / Calvet Seral, Juan / Aguilera, Antonio / Milagro Beamonte, Ana / Martinez Sapina, Ana / Barbeito, Gema / Perez del Molino, Maria Luisa / Gonzalo-Asensio, Jesus

medRxiv

Abstract: Discrepancies exist in Cycle threshold (Ct) values during detection of SARS-CoV-2 by qRT-PCR. We demonstrate that Ct values depend on the position of the target gene in the viral genome. Simultaneous detection of five genes in positive samples revealed ... ...

Abstract	Discrepancies exist in Cycle threshold (Ct) values during detection of SARS-CoV-2 by qRT-PCR. We demonstrate that Ct values depend on the position of the target gene in the viral genome. Simultaneous detection of five genes in positive samples revealed lower Ct values as we move further to the 3 end (orf1AB/RdRp>E>M>orf7a>N). These findings were confirmed in a retrospective analysis with 363 positive clinical samples. Our findings have key implications in clinical diagnostics of SARS-CoV-2, patient management and public health interventions.
Keywords	covid19
Language	English
Publishing date	2021-08-31
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.08.30.21262536
Database	COVID19

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Article ; Online: Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain.

Cañada, Javier E / Delgado, Elena / Gil, Horacio / Sánchez, Mónica / Benito, Sonia / García-Bodas, Elena / Gómez-González, Carmen / Canut-Blasco, Andrés / Portu-Zapirain, Joseba / Sáez de Adana, Ester / De la Peña, Mireia / Ibarra, Sofía / Cilla, Gustavo / Iribarren, José Antonio / Martínez-Sapiña, Ana / Thomson, Michael M

Viruses

2021 Volume 13, Issue 1

Abstract: The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from ... ...

Abstract	The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.
MeSH term(s)	Genetic Variation ; Genome, Viral ; Genotype ; HIV Infections/epidemiology ; HIV Infections/virology ; HIV-1/classification ; HIV-1/genetics ; Humans ; Molecular Epidemiology ; Phylogeny ; Phylogeography ; Public Health Surveillance ; Recombination, Genetic ; Sequence Analysis, DNA ; Spain/epidemiology ; Viremia
Language	English
Publishing date	2021-01-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13010093
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Article ; Online: Effectiveness and security of chronic hepatitis C treatment in coinfected patients in real-world.

Uriarte-Pinto, Moisés / Navarro-Aznarez, Herminia / De La Llama-Celis, Natalia / Arazo-Garcés, Piedad / Martínez-Sapiña, Ana María / Abad-Sazatornil, María Reyes

International journal of clinical pharmacy

2018 Volume 40, Issue 3, Page(s) 608–616

Abstract: Background HIV-HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. However, due to the lack of representativeness of ... ...

Abstract	Background HIV-HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. However, due to the lack of representativeness of coinfected patients in clinical trials, it is important to know real-world results. Objective To evaluate DAA treatment effectiveness in coinfected patients. We also analyse safety profile of DAA treatment and drug interactions between HCV and HIV therapy. Setting Descriptive study carried in a tertiary hospital of Spain Method HIV-HCV coinfected patients treated with DAAs between November 2014 and June 2016 were included. Main outcome measure Efficacy was measured in terms of sustained virologic response at week 12 after the end of therapy. Adverse events that led to treatment discontinuation were registered to evaluate the safety profile, and also drug interactions between DAAs and antiretroviral treatment were evaluated. Results Main HCV genotypes were 1a (34.9%) and 4 (24.5%). 51.9% were HCV previously treated, 54.7% had grade 4 liver fibrosis. SVR12 was reported in 90.6%. HCV treatment was well tolerated and there were no discontinuations because of adverse events. 30.2% of HIV treatments had to be modified before DAA treatment was started due to interactions, HIV suppression was not compromised. Conclusion DAA treatment in coinfected patients seems to be highly effective and secure. Evaluation of drug interactions must be a priority in order to maximize effectiveness and avoid toxicity.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Coinfection/complications ; Coinfection/drug therapy ; Drug Interactions ; Drug Therapy, Combination/adverse effects ; Female ; HIV Infections/complications ; HIV Infections/drug therapy ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Humans ; Male ; Middle Aged ; Treatment Outcome
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2018-03-20
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	2601204-2
ISSN	2210-7711 ; 2210-7703 ; 0928-1231
ISSN (online)	2210-7711
ISSN	2210-7703 ; 0928-1231
DOI	10.1007/s11096-018-0621-0
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Article ; Online: Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

Cuypers, Lize / Pérez, Ana Belén / Chueca, Natalia / Aldamiz-Echevarría, Teresa / Alados, Juan Carlos / Martínez-Sapiña, Ana María / Merino, Dolores / Pineda, Juan Antonio / Téllez, Francisco / Espinosa, Nuria / Salméron, Javier / Rivero-Juarez, Antonio / Vivancos, María Jesús / Hontañón, Víctor / Vandamme, Anne-Mieke / García, Féderico

PloS one

2018 Volume 13, Issue 7, Page(s) e0201268

Abstract: Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and ... ...

Abstract	Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.
MeSH term(s)	Antiviral Agents/therapeutic use ; Coinfection/drug therapy ; Coinfection/transmission ; Coinfection/virology ; Genome, Viral ; HIV Infections/drug therapy ; HIV Infections/transmission ; HIV Infections/virology ; Hepatitis C/genetics ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/transmission ; Hepatitis C, Chronic/virology ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Recurrence
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2018-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0201268
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Article ; Online: Author Correction: Identification of CRF89_BF, a new member of an HIV-1 circulating BF intersubtype recombinant form family widely spread in South America.

Delgado, Elena / Fernández-García, Aurora / Pérez-Losada, Marcos / Moreno-Lorenzo, María / Fernández-Miranda, Ismael / Benito, Sonia / Montero, Vanessa / Gil, Horacio / Hernáez, Silvia / Muñoz, Josefa / Zubero-Sulibarria, Miren Z / García-Bodas, Elena / Sánchez, Mónica / Del Romero, Jorge / Rodríguez, Carmen / Elorduy, Luis / Bereciartua, Elena / Culebras, Esther / Rodríguez-Avial, Icíar /

Giménez-Alarcón, María Luisa / Martín-Salas, Carmen / Gómez-González, Carmen / García-Irure, José J / Cenzual, Gema / Martínez-Sapiña, Ana / Maiques-Camarero, María / Pérez-Álvarez, Lucía / Thomson, Michael M

Scientific reports

2021 Volume 11, Issue 1, Page(s) 16115

Language	English
Publishing date	2021-08-03
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-95679-z
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Article ; Online: Identification of CRF89_BF, a new member of an HIV-1 circulating BF intersubtype recombinant form family widely spread in South America.

Scientific reports

2021 Volume 11, Issue 1, Page(s) 11442

Abstract: Circulating recombinant forms (CRFs) contribute substantially to the HIV-1 pandemic. Among 105 CRFs described in the literature, 16 are BF intersubtype recombinants, most of South American origin, of which CRF12_BF is the most widely spread. A BF ... ...

Abstract	Circulating recombinant forms (CRFs) contribute substantially to the HIV-1 pandemic. Among 105 CRFs described in the literature, 16 are BF intersubtype recombinants, most of South American origin, of which CRF12_BF is the most widely spread. A BF recombinant cluster identified in Bolivia was suggested to represent a new CRF_BF. Here we find that it belongs to a larger cluster incorporating 39 viruses collected in 7 countries from 3 continents, 22 of them in Spain, most from Bolivian or Peruvian individuals, and 12 in South America (Bolivia, Argentina, and Peru). This BF cluster comprises three major subclusters, two associated with Bolivian and one with Peruvian individuals. Near full-length genome sequence analyses of nine viruses, collected in Spain, Bolivia, and Peru, revealed coincident BF mosaic structures, with 13 breakpoints, 6 and 7 of which coincided with CRF12_BF and CRF17_BF, respectively. In a phylogenetic tree, they grouped in a clade closely related to these CRFs, and more distantly to CRF38_BF and CRF44_BF, all circulating in South America. These results allowed to identify a new HIV-1 CRF, designated CRF89_BF. Through phylodynamic analyses, CRF89_BF emergence was estimated in Bolivia around 1986. CRF89_BF is the fifth CRF member of the HIV-1 recombinant family related to CRF12_BF.
MeSH term(s)	Adult ; Female ; Genetic Variation ; Genome, Viral ; HIV Infections/epidemiology ; HIV Infections/genetics ; HIV-1/genetics ; Humans ; Male ; Middle Aged ; Phylogeny ; Recombination, Genetic ; Sequence Analysis, DNA ; South America/epidemiology
Language	English
Publishing date	2021-06-01
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-90023-x
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Article ; Online: High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

Pérez, Ana Belén / Chueca, Natalia / García-Deltoro, Miguel / Martínez-Sapiña, Ana María / Lara-Pérez, María Magdalena / García-Bujalance, Silvia / Aldámiz-Echevarría, Teresa / Vera-Méndez, Francisco Jesús / Pineda, Juan Antonio / Casado, Marta / Pascasio, Juan Manuel / Salmerón, Javier / Alados-Arboledas, Juan Carlos / Poyato, Antonio / Téllez, Francisco / Rivero-Juárez, Antonio / Merino, Dolores / Vivancos-Gallego, María Jesús / Rosales-Zábal, José Miguel /

García, Federico

Journal of hepatology

2019 Volume 71, Issue 5, Page(s) 876–888

Abstract: Background & aims: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing ... ...

Abstract	Background & aims: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. Methods: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded. Results: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. Conclusions: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. Lay summary: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.
MeSH term(s)	Anilides/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Benzimidazoles/therapeutic use ; Carbamates/therapeutic use ; Cyclopropanes/therapeutic use ; Drug Resistance, Viral/genetics ; Drug Therapy, Combination ; Female ; Fluorenes/therapeutic use ; Genotype ; Hepacivirus/genetics ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Hepatitis C/virology ; Humans ; Imidazoles/therapeutic use ; Lactams, Macrocyclic/therapeutic use ; Male ; Middle Aged ; Proline/analogs & derivatives ; Proline/therapeutic use ; Prospective Studies ; Pyrrolidines ; Retreatment ; Ribavirin/therapeutic use ; Ritonavir/therapeutic use ; Sofosbuvir/therapeutic use ; Spain/epidemiology ; Sulfonamides/therapeutic use ; Sustained Virologic Response ; Valine/analogs & derivatives ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/genetics
Chemical Substances	Anilides ; Antiviral Agents ; Benzimidazoles ; Carbamates ; Cyclopropanes ; Fluorenes ; Imidazoles ; Lactams, Macrocyclic ; Pyrrolidines ; Sulfonamides ; Viral Nonstructural Proteins ; ledipasvir, sofosbuvir drug combination ; ombitasvir (2302768XJ8) ; Ribavirin (49717AWG6K) ; Proline (9DLQ4CIU6V) ; NS-5 protein, hepatitis C virus (EC 2.7.7.48) ; Valine (HG18B9YRS7) ; daclatasvir (LI2427F9CI) ; Ritonavir (O3J8G9O825) ; paritaprevir (OU2YM37K86) ; Sofosbuvir (WJ6CA3ZU8B)
Language	English
Publishing date	2019-07-04
Publishing country	Netherlands
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2019.06.022
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