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Characteristics of ...
Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals
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- Howe, Anita Y. M. (författare)
- British Columbia Ctr Dis Control, 655 West 12th Ave, Vancouver, BC V5Z 4R4, Canada
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- Rodrigo, Chaturaka (författare)
- UNSW Sydney, Sch Med Sci, Sydney, NSW, Australia
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- Cunningham, Evan B. (författare)
- UNSW Sydney, Kirby Inst, Sydney, NSW, Australia
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- Douglas, Mark W. (författare)
- Univ Sydney, Storr Liver Ctr, Westmead Inst Med Res, Westmead Hosp, Westmead, NSW 2145, Australia
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- Dietz, Julia (författare)
- Goethe Univ, Univ Hosp, Dept Internal Med 1, Frankfurt, Germany
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- Grebely, Jason (författare)
- UNSW Sydney, Kirby Inst, Sydney, NSW, Australia
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- Popping, Stephanie (författare)
- Erasmus MC, Dept Virosci, Rotterdam, Netherlands
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- Sfalcin, Javier Alejandro (författare)
- Lab CIBIC, Rosario, Argentina
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- Parczewski, Milosz (författare)
- Pomeranian Med Univ, Dept Infect Trop Dis & Immune Deficiency, Szczecin, Poland
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- Sarrazin, Christoph (författare)
- Goethe Univ, Univ Hosp, Dept Internal Med 1, Frankfurt, Germany.;St Josefs Hosp, Med Clin, Wiesbaden, Germany
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- de Salazar, Adolfo (författare)
- Hosp Univ Clin San Cecilio, Inst Invest IbsGranada, CIBER Enfermedades Infecciosas CIBERINFEC, Granada, Spain
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- Fuentes, Ana (författare)
- Hosp Univ Clin San Cecilio, Inst Invest IbsGranada, CIBER Enfermedades Infecciosas CIBERINFEC, Granada, Spain
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- Sayan, Murat (författare)
- Kocaeli Univ, Kocaeli Educ & Res Hosp, PCR Unit, Kocaeli, Turkey.;Near East Univ, DESAM Inst, Nicosia, Northern Cyprus, Turkey
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- Quer, Josep (författare)
- Vall dHebron Inst Recerca VHIR, CIBEREHD, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain
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- Kjellin, Midori (författare)
- Uppsala universitet,Infektionsmedicin,Klinisk mikrobiologi
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- Kileng, Hege (författare)
- Univ Hosp North Norway, Dept Gastroenterol, Div Internal Med, Tromso, Norway
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- Mor, Orna (författare)
- Sheba Med Ctr, Cent Virol Lab, Minist Hlth, Ramat Gan, Israel.;Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel
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- Lennerstrand, Johan (författare)
- Uppsala universitet,Klinisk mikrobiologi
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- Fourati, Slim (författare)
- Henri Mondor Hosp, Natl Reference Ctr Viral Hepatitis BC & D, Dept Virol, Creteil, France.;INSERM U955, Creteil, France
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- Di Maio, Velia Chiara (författare)
- Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy
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- Chulanov, Vladimir (författare)
- Natl Med Res Ctr TB & Infect Dis, Moscow, Russia.;Sechenov Univ, Dept Infect Dis, Moscow, Russia.;Sirius Univ Sci & Technol, Soci, Russia
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- Pawlotsky, Jean-Michel (författare)
- Henri Mondor Hosp, Natl Reference Ctr Viral Hepatitis BC & D, Dept Virol, Creteil, France.;INSERM U955, Creteil, France
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- Harrigan, P. Richard (författare)
- Univ British Columbia, Vancouver, BC, Canada
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- Ceccherini-Silberstein, Francesca (författare)
- Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy
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- Garcia, Federico (författare)
- Hosp Univ Clin San Cecilio, Inst Invest IbsGranada, CIBER Enfermedades Infecciosas CIBERINFEC, Granada, Spain
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- Engelska.
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 4:5
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure.Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in >-1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing >-2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4.Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- RAS
- HCV
- DAA
- virologic failure
- NS5A
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- art (ämneskategori)
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Howe, Anita Y. M ...
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Rodrigo, Chatura ...
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Cunningham, Evan ...
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Douglas, Mark W.
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Dietz, Julia
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Grebely, Jason
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visa fler...
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Popping, Stephan ...
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Sfalcin, Javier ...
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Parczewski, Milo ...
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Sarrazin, Christ ...
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de Salazar, Adol ...
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Fuentes, Ana
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Sayan, Murat
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Quer, Josep
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Kjellin, Midori
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Kileng, Hege
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Mor, Orna
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Lennerstrand, Jo ...
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Fourati, Slim
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Di Maio, Velia C ...
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Chulanov, Vladim ...
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Pawlotsky, Jean- ...
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Harrigan, P. Ric ...
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Ceccherini-Silbe ...
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Garcia, Federico
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MEDICIN OCH HÄLS ...
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