34 results on '"O. Crosbie"'
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2. Resolution of paraneoplastic bile duct paucity following successful treatment of Hodgkin's disease
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O Crosbie
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Hepatology - Published
- 1997
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3. Irish nephrological society
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J. Farrell, D. Gill, G. Doyle, J. J. Walshe, C. Barry-Kinsella, M. Doyle, J. Walshe, V. E. Abernathy, D. J. Murnaghan, J. Higgins, M. Darling, A. Halligan, E. O’Brien, R. Conroy, D. Middleton, J. Martin, J. F. Douglas, J. Vella, P. Burke, D. Hickey, C. Staunton, D. Little, F. Keeling, J. O’Callaghan, D. Bouchier-Hayes, M. Carmody, J. Donohoe, A. Buckley, N. O’Meara, M. McMahon, C. J. Cronin, J. A. Jefferson, A. P. Maxwell, C. C. Doherty, A. E. Hughes, N. C. Nevin, G. Browne, J. A. B. Keogh, G. D. Wright, S. Spencer, R. Spencer, D. Murphy, D. G. Fogarty, E. Campbell, G. Thomas, D. Kelly, O. Crosbie, J. Hegarty, C. Crowley, A. Watson, B. Keogh, V. Tormey, P. Conlon, J. Horgan, D. B. Stafford, J. Johnson, B. G. Murphy, A. Yong, P. T. McNamee, S. Leavey, D. O’Neill, and S. Jennings
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medicine.medical_specialty ,Irish ,business.industry ,Family medicine ,language ,Medicine ,General Medicine ,business ,language.human_language - Published
- 1995
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4. Irish Society of Gastroenterology
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M. Woods, L. J. D. O’Donnell, B. Battistini, T. Warner, J. Vane, M. G. Fartming, J. Yaqoob, J. J. Wu, L. A. Norris, M. I. Khan, P. W. N. Keeling, D. Maguire, G. O’Sullivan, B. Harvey, B. Curran, Y. Xin∘, E. W. Kay, M. Leader, K. Henry, O. Crosbie, S. Norris, P. Costello, C. O’Farrelly, J. Hegarty, B. Kennedy, M. Duggan, R. Plant, E. K. Kenny-Walsh, P. Cotter, M. J. Whelton, M. Maloney, N. Noonan, M. Buckley, H. Hamilton, S. Beattie, C. O’Morain, B. McNamara, J. Cuffe, R. A. Barry, D. A. Collins, G. C. O’Sullivan, J. K. Collins, F. Shanahan, M. M. Skelly, H. E. Mulcahy, A. Troy, T. Connell, C. Duggan, M. J. Duffyt, K. Sheahan, D. P. O’Donoghue, H. X. Xia, D. Hyde, M. G. O’Brien, E. F. Fitzgerald, G. Lee, A. J. Hussey, T. J. Boyle, B. Garrihy, O. P. Clinton, O. J. McAnena, G. O’Sulllvan, H. Corby, V. Donnelly, C. O’Herlihy, P. R. O’Connell, T. Deignan, J. Kelly, N. P. Breslin, C. MacDonnell, J. O’Keeffe, K. Mills, U. Srinivasan, R. Willoughby, C. Feighery, B. Twohig, K. Gaynor, P. F. O’Regan, S. Duggan, H. P. Redmond, J. McCarthy, D. Bouchier-Hayes, Q. Y. Ma, K. E. Williamson, B. J. Rowlands, A. Tobin, R. Pilkington, M. O’Donnell, E. O’Shea, A. Conroy, G. Kaminski, A. Walsh, I. J. Temperley, D. Kelleher, D. G. Weir, M. K. Barry, E. D. Mulligan, M. A. Stokes, M. G. O’Riordain, T. F. Gorey, K. F. McGeeney, J. M. Fitzpatrick, R. W. G. Watson, J. H. Wang, F. Campbell, D. Bennett, E. Kavanagh, P. O. Gorman, P. O’Regan, M. M. I. Yassin, M. McCaigue, T. G. Parks, A. A. B. Barros D’Sa, M. Lawlor, S. McElwaine, M. A. Heneghan, M. Kerins, J. Goulding, E. L. Egan, F. M. Stevens, C. F. McCarthy, M. Quirke, A. M. Eustace-Ryan, S. Qureshi, E. Aziz, A. Maree, S. Collins, T. Browne, S. Ahmed, B. O. Sullibhan, P. Smith, F. Walker, F. O’Connor, E. Sweeney, R. J. Farrell, M. Morrint, M. Goggins, and J. G. McNulty
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medicine.medical_specialty ,Irish ,business.industry ,Ophthalmology ,language ,medicine ,Library science ,General Medicine ,business ,language.human_language - Published
- 1995
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5. Irish Society of Gastroenterology
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D. F. Smith, N. Leonard, Michael J. Kerin, Brian J. Harvey, M. Duggan, Jiang Huai Wang, S. McDonald, J. S. A. Collins, Malachi J. McKenna, Frank B. V. Keane, Cormac T. Taylor, E. Mulligan, C. Kelly, N. Fanning, M. G. Goggins, David Bouchier-Hayes, W. A. Tanner, T. Hogan, F. Barker, S. Keating, B. T. Johnston, W. R.F. Ferguson, G. Thornton, Oliver J. McAnena, Colm O'Morain, G. P. McEntee, U. Srinivasan, K. B. Bamford, Alan W. Baird, Éanna J Ryan, O. Crosbie, A. Whelan, J. Crowe, Simon Keely, Terry Boyle, A. Pryde, J. Carton, Derek Moriarty, F. O’Brien, Niall Breslin, M. O’Riordain, S. Montague C. O'Morain, B. Crowley, N. McCallion, K. Synnott, D. P. O'Donoghoe, N. A. Parfrey, P. McEneaney, P. MacMathuna, Claire Condron, M. K. Barry, D. P. O’Donoghue, S. Doyle, T. P. J. Hennessy, Henry Paul Redmond, S. Beattie, J. M. Sloan, T. N. Walsh, J. K. Collins, M. Casey, R. B. Mooney, O. P. Clinton, M. A. Stokes, Cliona O'Farrelly, John M. Fitzpatrick, Dermot Kelleher, K. F. McGeeney, S. Duggan, I. Frazer, C. Feighery, H. Hamilton, A. G. Shattock, C. McCormick, Diarmuid O'Donoghue, P. McGurgan, G. O'Sullivan, K. C. Trimble, X. J. Fan, Thomas F. Gorey, P. R. O'Connell, D. Carroll, N. Mahmud, Margaret O'Mahony, G. Kelly, N. I. McDougall, T. C. K. Tham, L. Madrigal, Javed Yakoob, Peter J. Kelly, S. Douglas, R. C. Heading, J. Quinn, Gerald C. O'Sullivan, P. Lawlor, J. P. O'Donoghue, D. Maguire, Andrew H.G. Love, D. Booth, D. J. Reen, M. M. Skelly, D. Graham, E. M. Murray, Paul G. Horgan, F. Campbell, J. F. Fielding, X. G. Fan, K. Mealy, Donald G. Weir, R. Merriman, A. Long, R. C. Stuart, A. Keaveny, M. G. O'Sullivan, A. E. Brannigan, J. M. O≿donoghue, C. Morrison, A. Conroy, R. J. McFarland, S. Sachithanandan, Rosemarie Freaney, J. Lennon, Patrick J. Byrne, S. Al-Bloushi, P. Gillen, J. P. McGrath, G. S. A. McDonald, A. Weerkamp, R. G. P. Watson, C. Scanlon, P. W. N. Keeling, J. Hegarty, Maria M. Buckley, J. Mathias, M. C. Regan, Fergus Shanahan, R. W. G. Watson, K. Barry, M. G. Courtney, and Suzanne Norris
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medicine.medical_specialty ,Irish ,business.industry ,Ophthalmology ,language ,Medicine ,Library science ,General Medicine ,business ,language.human_language - Published
- 1994
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6. Irish society of gastroenterology
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M. Stack, R. G. K. Watson, David Bouchier-Hayes, P. R. O'Connell, Thomas N. Walsh, N. Noonan, D. Morrissey, J. Barrett, A. Husain, X. J. Fan, D. P. O’Donoghue, L. Madrigal, O. Crosbie, J. K. Collins, J. Morgan, M. T. P. Caldwell, Alan W. Baird, R. A. J. Spence, Simon Keely, Padraic MacMathuna, M. Moloney, Claire Condron, A. Finch, E. F. A. Spencer, S. G. Marshall, Brian J. Harvey, Jiang Huai Wang, H. Xia, X. G. Fan, K. Mealy, D. Maguire, K. M. Murphy, Hugh Mulcahy, M. O’Riordain, Fergal J. O'Brien, R. G. P. Watson, I. Frazier, N. Mahmud, John R. Kelly, M. Madden, D. McMaster, Patrick J. Byrne, David Gibbons, J. Crowe, G. O. Sullivan, Fergus Shanahan, C. A. Whelan, W. O. Kirwan, R. W. Parks, T. P. J. Hennessey, Alexander C.O. Evans, G. McEntee, E. Clarke, C. B. O’Suilleabhain, C. Kanduru, P. W. N. Keeling, J. Farrell, Henry Paul Redmond, R. W. G. Watson, Diarmuid O'Donoghue, M. J. Crowley, D. Lynch, O. Traynor, Sally Ann Lynch, E. M. Mcllrath, C. Feighery, T. P. J. Hennessy, P. Marks, Peter J. Kelly, John Hyland, H. J. Windle, Richard J. Farrell, D. Graham, Peter McCarthy, Colm O'Herlihy, D. G. Weir, P. L. Yeoh, Cliona O'Farrelly, N. A. Parfrey, J. Lennon, M. I. Khan, Michael J. Duffy, Gerald C. O'Sullivan, V. S. Donnelly, M. Crowley, M. O’Brien, M. M. Skelly, Mary Barry, A. K. Cherukuri, J. Carton, J. Hegarty, S. Reid, P. Quinn, G. Lee, G. W. Johnson, Paul G. Horgan, R. Merriman, T. G. Parks, Paul Neary, E. Fitzgerald, G. S. A. McDonald, P. White, C. Devereux, P. O’Leary, Y. T. Chuan, M. Borton, Suzanne Norris, W. A. Stack, Kieran Sheahan, R. McManus, S. A. McMillan, Dermot Kelleher, and D. J. Waldron
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Irish ,business.industry ,language ,engineering ,Optometry ,Library science ,Medicine ,General Medicine ,Cork ,engineering.material ,business ,language.human_language - Published
- 1994
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7. Management of Hereditary Haemochromatosis: A Retrospective Audit at Cork University Hospital
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O. Crosbie, S. O'Mahony, and J. McCarthy
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medicine.medical_specialty ,Pediatrics ,Hereditary haemochromatosis ,business.industry ,Family medicine ,Gastroenterology ,medicine ,Audit ,business ,University hospital - Published
- 2004
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8. Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis.
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A, McCormick P, H, Ooi, and O, Crosbie
- Abstract
BACKGROUND: It is believed that severe portal hypertensive gastropathy probably accounts for most non-variceal bleeding episodes in patients with cirrhosis. Gastric antral vascular ectasia (GAVE) also occurs in these patients. It is not clear whether it is a variant of portal hypertensive gastropathy or a distinct condition. PATIENT: A patient, a 66 year od woman, with cirrhosis initially diagnosed as having portal hypertensive gastropathy and subsequently classified as GAVE is described. She required transfusion with a total of 130 units of packed red cells for gastrointestinal blood loss. RESULTS: The bleeding did not respond to portal decompression with TIPS or beta blockers. Following treatment with oral tranexamic acid she has not required further blood transfusion over a period of 30 months. CONCLUSION: Tranexamic acid may be a useful treatment for refractory bleeding due to gastric antral vascular ectasia in patients with cirrhosis.
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- 1998
9. Hepatitis C community prevalence is over-estimated: a prospective, birth cohort study.
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McCormick PA, O'Grady M, De Gascun CF, Lambert JS, Crosbie O, McKiernan S, Skelly M, Holder P, Courtney G, Hennessy B, Walsh K, Twohig R, Browne K, O'Gorman T, Crowley V, Costelloe SJ, O'Byrne R, Whitney E, Gildea O, and Montgomery N
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- Humans, Ireland epidemiology, Male, Female, Prevalence, Prospective Studies, Middle Aged, Birth Cohort, Hepatitis C Antibodies blood, Adult, Seroepidemiologic Studies, Hepatitis C Antigens blood, Aged, Cohort Studies, Hepatitis C epidemiology, Hepatitis C diagnosis
- Abstract
Background: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence., Aims: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985., Methods: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated., Results: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin., Conclusions: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered., (© 2024. The Author(s).)
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- 2024
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10. Erratum: Alcohol dependency in the elderly - are we capturing it?
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Murphy C, Buckley M, Kearns R, O'Sullivan A, Malik Y, Gallagher P, and Crosbie O
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- 2018
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11. Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s.
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Garvey P, Murphy N, Flanagan P, Brennan A, Courtney G, Crosbie O, Crowe J, Hegarty J, Lee J, McIver M, McNulty C, Murray F, Nolan N, O'Farrelly C, Stewart S, Tait M, Norris S, and Thornton L
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- Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic virology, Humans, Liver Cirrhosis etiology, Liver Neoplasms etiology, Middle Aged, Young Adult, Drug Contamination, Hepatitis C, Chronic complications, Rho(D) Immune Globulin adverse effects
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Background & Aim: In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression., Methods: We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression., Results: Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8])., Conclusions: Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history., Lay Summary: In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2017
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12. Effectiveness of interferon-free therapy for the treatment of HCV-patients with compensated cirrhosis treated through the Irish early access program.
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Gray E, O'Leary A, Bergin C, Cannon M, Courtney G, Crosbie O, De Gascun CF, Fanning LJ, Feeney E, Houlihan DD, Kelleher B, Lambert JS, Lee J, Mallon P, McConkey S, McCormick A, McKiernan S, McNally C, Murray F, Sheehan G, Stewart S, Walsh C, and Norris S
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- Adult, Antiviral Agents adverse effects, Benzimidazoles adverse effects, Drug Therapy, Combination, Female, Fluorenes adverse effects, Genotype, Hepacivirus genetics, Hepacivirus growth & development, Hepatitis C complications, Hepatitis C diagnosis, Hepatitis C mortality, Humans, Ireland, Liver Cirrhosis diagnosis, Liver Cirrhosis mortality, Liver Cirrhosis virology, Longitudinal Studies, Male, Middle Aged, Program Evaluation, Prospective Studies, Registries, Ribavirin adverse effects, Sofosbuvir, Sustained Virologic Response, Time Factors, Treatment Outcome, Uridine Monophosphate adverse effects, Uridine Monophosphate therapeutic use, Antiviral Agents therapeutic use, Benzimidazoles therapeutic use, Fluorenes therapeutic use, Health Services Accessibility, Hepacivirus drug effects, Hepatitis C drug therapy, Liver Cirrhosis drug therapy, Ribavirin therapeutic use, Uridine Monophosphate analogs & derivatives
- Abstract
Background: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV)., Method: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined., Results: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV). The discontinuation rate was 5% and the on-treatment mortality rate was 1%., Conclusion: The availability of interferon-free regimens represents a significant breakthrough for the treatment of HCV infection. Treatments options, with high SVR12 rates, are now available for patients with compensated cirrhosis who were unsuitable for treatment with interferon-based regimens. Data obtained from studies conducted in real world practice provide robust information fundamental for input into future economic evaluations for agents used for the treatment of HCV infection.
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- 2017
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13. Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus.
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Naik AS, Owsianka A, Palmer BA, O'Halloran CJ, Walsh N, Crosbie O, Kenny-Walsh E, Patel AH, and Fanning LJ
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- Antibodies, Viral biosynthesis, Hepacivirus pathogenicity, Hepatitis C, Chronic immunology, Hepatitis C, Chronic virology, Humans, Neutralization Tests, Viral Envelope Proteins immunology, Virulence, Epitope Mapping methods, Hepacivirus immunology, Viral Envelope Proteins chemistry
- Abstract
The humoral immune system responds to chronic hepatitis C virus (HCV) infection by producing neutralising antibodies (nAb). In this study we generated three HCV pseudoparticles in which E1E2 glycoprotein sequence was targeted by the host humoral immune system. We used patient derived virus free Fabs (VF-Fabs) obtained from HCV genotype 1a (n = 3), genotype 1b (n = 7) and genotype 3a (n = 1) for neutralisation of HCVpp produced in this study both individually and in combination. Based on the available anti-HCV monoclonal nAb mapping information we selected amino acid region 384-619 for conformational epitope mapping. Amongst our notable findings, we observed significant reduction in HCVpp infectivity (p<0.05) when challenged with a combination of inter genotype and subtype VF-Fabs. We also identified five binding motifs targeted by patient derived VF-Fab upon peptide mapping, of which two shared the residues with previously reported epitopes. One epitope lies within an immunodominant HVR1 and two were novel. In summary, we used a reverse epitope mapping strategy to identify preferred epitopes by the host humoral immune system. Additionally, we have combined different VF-Fabs to further reduce the HCVpp infectivity. Our data indicates that combining the antigen specificity of antibodies may be a useful strategy to reduce (in-vitro) infectivity.
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- 2017
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14. Ultradeep Pyrosequencing of Hepatitis C Virus to Define Evolutionary Phenotypes.
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Palmer BA, Dimitrova Z, Skums P, Crosbie O, Kenny-Walsh E, and Fanning LJ
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Analysis of hypervariable regions (HVR) using pyrosequencing techniques is hampered by the ability of error correction algorithms to account for the heterogeneity of the variants present. Analysis of between-sample fluctuations to virome sub-populations, and detection of low frequency variants, are unreliable through the application of arbitrary frequency cut offs. Cumulatively this leads to an underestimation of genetic diversity. In the following technique we describe the analysis of Hepatitis C virus (HCV) HVR1 which includes the E1/E2 glycoprotein gene junction. This procedure describes the evolution of HCV in a treatment naïve environment, from 10 samples collected over 10 years, using ultradeep pyrosequencing (UDPS) performed on the Roche GS FLX titanium platform ( Palmer et al. , 2014 ). Initial clonal analysis of serum samples was used to inform downstream error correction algorithms that allowed for a greater sequence depth to be reached. PCR amplification of this region has been tested for HCV genotypes 1, 2, 3 and 4., (Copyright © 2017 The Authors; exclusive licensee Bio-protocol LLC.)
- Published
- 2017
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15. Humoral immune system targets clonotypic antibody-associated hepatitis C virus.
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Naik AS, Palmer BA, Crosbie O, Kenny-Walsh E, and Fanning LJ
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- Amino Acid Sequence, Endopeptidase K chemistry, Epitope Mapping, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Immunoglobulin Fab Fragments genetics, Immunoglobulin Fab Fragments immunology, Neutralization Tests, Serum chemistry, Serum immunology, Viral Envelope Proteins genetics, Viral Proteins genetics, Viremia immunology, Hepacivirus immunology, Hepatitis C Antibodies immunology, Hepatitis C, Chronic immunology, Immunity, Humoral, Viral Envelope Proteins immunology, Viral Proteins immunology
- Abstract
Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430). Furthermore, we generated HCV pseudoparticles (HCVpp) derived from AAV sequences to assess their infectivity. We studied the neutralization potential of virus-free Fab obtained from antibody-virus complexes, in the HCVpp system. We observed selective targeting of clonotypic HCV variants from the quasispecies pool. Moreover, we identified potential neutralizing epitopes within the HVR1 and an additional epitope that overlapped with a broadly neutralizing AP33 epitope (amino acid 412-423 in E2). We observed a marked difference in the infectivity of HCVpp generated using E1E2 sequences isolated from AAV. We document reduction in the infectivity of HCVpp-H77 and HCVpp derived from AAV sequences when challenged with virus-free Fab. Our results provide novel insights into the complexities of engagement between HCV and the humoral immune system.
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- 2017
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16. High mortality during direct acting antiviral therapy for hepatitis C patients with Child's C cirrhosis: Results of the Irish Early Access Programme.
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Gray E, O'Leary A, Stewart S, Bergin C, Cannon M, Courtney G, Crosbie O, De Gascun CF, Fanning LJ, Feeney E, Houlihan DD, Kelleher B, Lambert JS, Lee J, Mallon P, McConkey S, McCormick A, McKiernan S, McNally C, Murray F, Sheehan G, and Norris S
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- Antiviral Agents, Child, Hepatitis C, Humans, Hepacivirus, Liver Cirrhosis
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- 2016
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17. A single amino acid change in the hypervariable region 1 of hepatitis C virus genotype 4a aids humoral immune escape.
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Naik AS, Palmer BA, Crosbie O, Kenny-Walsh E, and Fanning LJ
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- Hepacivirus genetics, Hepatitis C Antibodies blood, Humans, Longitudinal Studies, RNA, Viral genetics, Sequence Analysis, DNA, Hepacivirus immunology, Immune Evasion, Mutant Proteins genetics, Mutant Proteins immunology, Mutation, Missense, Viral Proteins genetics, Viral Proteins immunology
- Abstract
Longitudinal analysis of chronic hepatitis C virus (HCV) infection has shown that the virus has several adaptive strategies that maintain persistence and infectivity over time. We examined four serum samples from the same chronically infected HCV genotype 4a patient for the presence of IgG antibody-associated virus. RNA was isolated from antibody-associated and antibody-free virions. Subsequent to sequence analysis, 27 aa hypervariable region 1 (HVR1) peptides were used to test the humoral immune escape. We demonstrated that differential peptide binding of Fab was associated with a single amino acid change. We provide direct evidence of natural humoral immune escape by HCV within HVR1.
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- 2016
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18. Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses.
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Palmer BA, Schmidt-Martin D, Dimitrova Z, Skums P, Crosbie O, Kenny-Walsh E, and Fanning LJ
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- Adult, Aged, Aging, Amino Acid Sequence, Amino Acid Substitution, Base Sequence, Female, Hepacivirus genetics, Hepatitis C, Chronic immunology, Humans, Immunity, Humoral immunology, Immunoglobulin G immunology, Liver Cirrhosis pathology, Male, Middle Aged, Molecular Sequence Data, Sequence Analysis, RNA, Viral Envelope Proteins genetics, Viral Proteins genetics, Young Adult, Antibodies, Neutralizing immunology, Hepacivirus immunology, Hepatitis C Antibodies immunology, Hepatitis C, Chronic virology, Viral Proteins immunology
- Abstract
Unlabelled: Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space., Importance: HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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19. Intensive temporal mapping of hepatitis C hypervariable region 1 quasispecies provides novel insights into hepatitis C virus evolution in chronic infection.
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Schmidt-Martin D, Crosbie O, Kenny-Walsh E, and Fanning LJ
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- Adult, Aged, Female, Hepacivirus classification, Hepacivirus metabolism, Humans, Male, Middle Aged, Molecular Sequence Data, Phylogeny, Selection, Genetic, Viral Proteins metabolism, Young Adult, Evolution, Molecular, Hepacivirus genetics, Hepatitis C, Chronic virology, Viral Proteins genetics
- Abstract
Hepatitis C virus (HCV) is an RNA virus which exists as swarms of closely related viruses known as quasispecies (QS). A number of studies have demonstrated associations between QS hypervariable region 1 (HVR1) characteristics (diversity and complexity) and treatment success. We investigated HCV QS change in chronic infection over intervals of 2-4 weeks in 23 chronically infected individuals to describe the natural history of virus evolution and establish whether HCV QS characteristics could be used to individualize treatment regimens at a molecular level. HVR1 QS diversity, complexity and divergence continue to change in an unpredictable fashion in chronic infection even where there is little phylogenetic change, which is likely to preclude the use of these features in treatment individualization. Our phylogenetic analysis identified no change in the HVR1 QS in 12 subjects, minor change in four subjects and we describe a time-ordered phylogeny for the first time over a period as short as 16 weeks in seven subjects. We identified the existence of multiple subpopulation infections using partitioned analysis of QS and illustrated how subpopulations were sequentially replaced in a number of subjects. We illustrated marked variation in the nucleotide substitution per codon position between patients with sequence change and those without change in the phylogenetic tree. Analysis of codon-specific selection pressures identified a number of codons under purifying selection, suggesting that these code for structurally conserved amino acids. We also identified sections of the HVR1 under positive selection with marked sequence heterogeneity, suggesting that these may be potential epitope-binding sites.
- Published
- 2015
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20. Analysis of the evolution and structure of a complex intrahost viral population in chronic hepatitis C virus mapped by ultradeep pyrosequencing.
- Author
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Palmer BA, Dimitrova Z, Skums P, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- High-Throughput Nucleotide Sequencing, Humans, Longitudinal Studies, Molecular Sequence Data, Genetic Variation, Hepacivirus classification, Hepacivirus genetics, Hepatitis C, Chronic virology, RNA, Viral genetics
- Abstract
Unlabelled: Hepatitis C virus (HCV) causes chronic infection in up to 50% to 80% of infected individuals. Hypervariable region 1 (HVR1) variability is frequently studied to gain an insight into the mechanisms of HCV adaptation during chronic infection, but the changes to and persistence of HCV subpopulations during intrahost evolution are poorly understood. In this study, we used ultradeep pyrosequencing (UDPS) to map the viral heterogeneity of a single patient over 9.6 years of chronic HCV genotype 4a infection. Informed error correction of the raw UDPS data was performed using a temporally matched clonal data set. The resultant data set reported the detection of low-frequency recombinants throughout the study period, implying that recombination is an active mechanism through which HCV can explore novel sequence space. The data indicate that polyvirus infection of hepatocytes has occurred but that the fitness quotients of recombinant daughter virions are too low for the daughter virions to compete against the parental genomes. The subpopulations of parental genomes contributing to the recombination events highlighted a dynamic virome where subpopulations of variants are in competition. In addition, we provide direct evidence that demonstrates the growth of subdominant populations to dominance in the absence of a detectable humoral response., Importance: Analysis of ultradeep pyrosequencing data sets derived from virus amplicons frequently relies on software tools that are not optimized for amplicon analysis, assume random incorporation of sequencing errors, and are focused on achieving higher specificity at the expense of sensitivity. Such analysis is further complicated by the presence of hypervariable regions. In this study, we made use of a temporally matched reference sequence data set to inform error correction algorithms. Using this methodology, we were able to (i) detect multiple instances of hepatitis C virus intrasubtype recombination at the E1/E2 junction (a phenomenon rarely reported in the literature) and (ii) interrogate the longitudinal quasispecies complexity of the virome. Parallel to the UDPS, isolation of IgG-bound virions was found to coincide with the collapse of specific viral subpopulations., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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21. Clinical relevance of detectable hepatitis C virus RNA in the context of direct-acting antivirals.
- Author
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O'Sullivan K, Levis J, Hegarty K, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- Humans, Hepacivirus genetics, Hepatitis C, Chronic blood, Hepatitis C, Chronic drug therapy, Oligopeptides therapeutic use, Proline analogs & derivatives, RNA, Viral blood
- Published
- 2013
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- View/download PDF
22. Insertion and recombination events at hypervariable region 1 over 9.6 years of hepatitis C virus chronic infection.
- Author
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Palmer BA, Moreau I, Levis J, Harty C, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- Amino Acid Sequence, Base Sequence, DNA, Viral genetics, Evolution, Molecular, Hepacivirus classification, Hepacivirus isolation & purification, Humans, Molecular Sequence Data, Mutagenesis, Insertional, Phylogeny, Recombination, Genetic, Sequence Homology, Nucleic Acid, Time Factors, Hepacivirus genetics, Hepatitis C, Chronic virology, Viral Proteins genetics
- Abstract
Hepatitis C virus (HCV) exists as a quasispecies within an infected individual. We have previously reported an in-frame 3 bp insertion event at the N-terminal region of the E2 glycoprotein from a genotype 4a HCV isolate giving rise to an atypical 28 aa hypervariable region (HVR) 1. To further explore quasispecies evolution at the HVR1, serum samples collected over 9.6 years from the same chronically infected, treatment naïve individual were subjected to retrospective clonal analysis. Uniquely, we observed that isolates containing this atypical HVR1 not only persisted for 7.6 years, but dominated the quasispecies swarm. Just as striking was the collapse of this population of variants towards the end of the sampling period in synchrony with variants containing a classical HVR1 from the same lineage. The replication space was subsequently occupied by a second minor lineage, which itself was only intermittently detectable at earlier sampling points. In conjunction with the observed genetic shift, the coexistence of two distinct HVR1 populations facilitated the detection of putative intra-subtype recombinants, which included the identification of the likely ancestral parental donors. Juxtaposed to the considerable plasticity of the HVR1, we also document a degree of mutational inflexibility as each of the HVR1 subpopulations within our dataset exhibited overall genetic conservation and convergence. Finally, we raise the issue of genetic analysis in the context of mixed lineage infections.
- Published
- 2012
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23. The pan-genotype specificity of the hepatitis C virus anti-core monoclonal antibody C7-50 is contingent on the quasispecies profile of a population.
- Author
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Palmer BA, Menton J, Levis J, Kenny-Walsh E, Crosbie O, and Fanning LJ
- Subjects
- Cell Line, Genotype, Hepacivirus classification, Hepatocytes virology, Humans, Molecular Sequence Data, RNA, Viral genetics, Sequence Analysis, DNA, Viral Core Proteins genetics, Antibodies, Monoclonal immunology, Hepacivirus genetics, Hepacivirus immunology, Hepatitis C Antibodies immunology, Polymorphism, Single Nucleotide, Viral Core Proteins immunology
- Abstract
The inter/intra-genotype quasispecies makeup of hepatitis C virus (HCV) has retarded the development of antibodies capable of pan-genotype reactivity. Mutations, even in conserved domains, are tolerated to a degree. In this report, we characterise the pan-genotype specificity of the commercially available monoclonal anti-HCV core antibody C7-50. We demonstrate the antibody's ability to detect HCV core protein following infection of Huh7 cells with serum-derived HCV of genotypes 2-5 and that a single-site polymorphism in a genotype 3a core amino acid sequence is sufficient to disrupt antibody recognition of the epitope. This same polymorphism is a feature of genotype 3 viruses.
- Published
- 2012
- Full Text
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24. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.
- Author
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Shanab AA, Scully P, Crosbie O, Buckley M, O'Mahony L, Shanahan F, Gazareen S, Murphy E, and Quigley EM
- Subjects
- Acute-Phase Proteins genetics, Acute-Phase Proteins metabolism, Adult, Breath Tests, Carrier Proteins genetics, Carrier Proteins metabolism, Female, Humans, Interleukin-8 genetics, Interleukin-8 metabolism, Lactulose metabolism, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Middle Aged, Toll-Like Receptor 4 genetics, Fatty Liver complications, Gene Expression Regulation physiology, Interleukin-8 blood, Intestine, Small microbiology, Toll-Like Receptor 4 metabolism
- Abstract
Background: Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS)., Aim: To compare the prevalence of SIBO and its relationships to LPS receptor levels and systemic cytokines in NASH patients and healthy control subjects., Methods: Eighteen NASH patients (eight males) and 16 age-matched and gender-matched healthy volunteers were studied. SIBO was assessed by the lactulose breath hydrogen test (LHBT), plasma lipopolysaccharide binding protein (LBP) levels by ELISA, and expression (as a percentage) of TLR-2 and 4 on CD14-positive cells by flow cytometry. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were measured in plasma., Results: SIBO was more common in NASH patients than control subjects (77.78% vs. 31.25%; P < 0.0001). LBP levels and TLR-2 expression were similar in both groups, TLR-4/MD-2 expression on CD14 positive cells was higher among NASH patients: expression, mean ± SEM, NASH vs. control: 20.95 ± 2.91% vs. 12.73 ± 2.29%, P < 0.05. Among the examined cytokines, only IL-8 levels were significantly higher in patients than control (P = 0.04) and correlated positively with TLR-4 expression (r = 0.5123, P = 0.036)., Conclusion: NASH patients have a higher prevalence of small intestinal bacterial overgrowth which is associated with enhanced expression of TLR-4 and release of IL-8. SIBO may have an important role in NASH through interactions with TLR-4 and induction of the pro-inflammatory cytokine, IL-8.
- Published
- 2011
- Full Text
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25. Histological changes in hepatitis C virus antibody-positive, hepatitis C virus RNA-negative subjects suggest persistent virus infection.
- Author
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Moreau I, Kenny-Walsh E, Crosbie O, and Fanning LJ
- Subjects
- Hepatitis C pathology, Humans, Liver pathology, Hepatitis C blood, Hepatitis C Antibodies blood, RNA, Viral blood
- Published
- 2009
- Full Text
- View/download PDF
26. Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.
- Author
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Moreau I, O'Sullivan H, Murray C, Levis J, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- Amino Acid Sequence, Genotype, Hepacivirus classification, Hepacivirus immunology, Hepatitis C virology, Humans, Molecular Sequence Data, Mutagenesis, Insertional, Phylogeny, Sequence Alignment, Hepacivirus genetics, Hepacivirus isolation & purification, Hepatitis C immunology, Hepatitis C Antibodies immunology, Immunoglobulin G immunology
- Abstract
Background: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms., Results: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction., Conclusion: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.
- Published
- 2008
- Full Text
- View/download PDF
27. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.
- Author
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Moreau I, Levis J, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- Adult, Antiviral Agents administration & dosage, Drug Therapy, Combination, Evolution, Molecular, Female, Genotype, Hepacivirus drug effects, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Interferon alpha-2, Interferon-alpha administration & dosage, Male, Middle Aged, Molecular Sequence Data, Phylogeny, Polyethylene Glycols administration & dosage, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Ribavirin administration & dosage, Sequence Analysis, DNA, Treatment Failure, Treatment Outcome, Viral Load, Virus Replication, Antiviral Agents therapeutic use, Genetic Variation, Hepacivirus classification, Hepatitis C, Chronic drug therapy, Interferon-alpha therapeutic use, Polyethylene Glycols therapeutic use, Ribavirin therapeutic use
- Abstract
Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.
- Published
- 2008
- Full Text
- View/download PDF
28. Symptomatic stent cast.
- Author
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Keohane J, Moore M, O'Mahony S, and Crosbie O
- Subjects
- Aged, 80 and over, Female, Gallstones prevention & control, Gallstones therapy, Humans, Lithotripsy, Prosthesis Failure, Recurrence, Reoperation, Bile Ducts surgery, Cholangiopancreatography, Endoscopic Retrograde, Gallstones etiology, Jaundice etiology, Stents adverse effects
- Abstract
Biliary stent occlusion is a major complication of endoscopic stent insertion and results in repeat procedures. Various theories as to the etiology have been proposed, the most frequently studied is the attachment of gram negative bacteria within the stent. Several studies have shown prolongation of stent patency with antibiotic prophylaxis. We report the case of stent occlusion from a cast of a previously inserted straight biliary stent; a "stent cast" in an 86-year-old woman with obstructive jaundice. This was retrieved with the lithotrypter and she made an uneventful recovery. This is the first reported case of a biliary stent cast.
- Published
- 2008
- Full Text
- View/download PDF
29. Serendipitous identification of natural intergenotypic recombinants of hepatitis C in Ireland.
- Author
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Moreau I, Hegarty S, Levis J, Sheehy P, Crosbie O, Kenny-Walsh E, and Fanning LJ
- Subjects
- Amino Acid Sequence, Hepacivirus classification, Hepacivirus isolation & purification, Hepatitis C virology, Humans, Ireland, Molecular Sequence Data, Nucleic Acid Hybridization, Sequence Alignment, Sequence Analysis, Protein, Viral Nonstructural Proteins chemistry, Viral Nonstructural Proteins genetics, Viral Proteins chemistry, Viral Proteins genetics, Genotype, Hepacivirus genetics, Recombination, Genetic
- Abstract
Background: Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5' untranslated region [5'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5'UTR of the genome by reverse line probe hybridisation [RLPH]., Results: The original diagnosis of a mixed genotype infection was not confirmed by clonal analysis of the NS5B region of the genome. The phylogenetic analysis indicated that both specimens were natural intergenotypic recombinant forms of HCV. The recombination was between genotypes 2k and 1b for both specimens. The recombination break point was identified as occurring within the NS2 region of the genome., Conclusion: The viral recombinants identified here resemble the recombinant form originally identified in Russia. The RLPH pattern observed in this study may be a signature indicative of this particular type of intergenotype recombinant of hepatitis C meriting clonal analysis of NS2.
- Published
- 2006
- Full Text
- View/download PDF
30. Comparison of three stool antigen assays with the 13C- urea breath test for the primary diagnosis of Helicobacter pylori infection and monitoring treatment outcome.
- Author
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Hooton C, Keohane J, Clair J, Azam M, O'Mahony S, Crosbie O, and Lucey B
- Subjects
- Adult, Carbon Isotopes, Dyspepsia etiology, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Urea, Antigens, Bacterial analysis, Breath Tests, Feces microbiology, Helicobacter Infections diagnosis, Helicobacter pylori immunology
- Abstract
Background: The urea breath test (UBT) is the gold-standard non-invasive test for the detection of Helicobacter pylori infection, however, the lack of availability of the UBT due to the high cost of the test, and in particular the need for expensive analytical instrumentation, limits the usefulness of this method. Stool antigen assays may offer an alternative non-invasive method for the diagnosis of infection., Objective: To compare the accuracy of three stool antigen assays (HpSA, IDEIA HpStAR, and ImmunoCard STAT) against the UBT for the primary diagnosis of H. pylori infection and for monitoring treatment outcome., Methods: A total of 102 patients attending two gastroenterology day-case clinics for the investigation of dyspepsia were included. Each patient provided breath and stool samples for analysis. Patients who tested positive for H. pylori by the validated UBT were prescribed triple therapy and invited to return for repeat breath and stool sample analysis 6 weeks post-treatment., Results: Of the 102 patients tested, 48 were diagnosed with H. pylori infection by the UBT. The HpSA assay interpreted 38 of these as positive (79% sensitive). Of the 54 UBT-negative patients the HpSA assay interpreted all 54 as negative (100% specific). The IDEIA HpStAR assay correctly identified 44 patients as positive (92% sensitive) and 50 as negative (92.5% specific). The ImmunoCard STAT assay interpreted 38 patients as positive (79% sensitive) and 52 as negative (96.3% specific)., Conclusion: The findings indicate that the IDEIA HpStAR stool antigen kit is the most accurate assay of the three assays evaluated, and possibly represents a viable alternative to the UBT for the primary diagnosis of H. pylori infection and for monitoring treatment outcome.
- Published
- 2006
- Full Text
- View/download PDF
31. Helicobacter pylori: prevalence of antimicrobial resistance in clinical isolates.
- Author
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Hooton C, Dempsey C, Keohane J, O'Mahony S, Crosbie O, and Lucey B
- Subjects
- Amoxicillin pharmacology, Anti-Bacterial Agents pharmacology, Clarithromycin pharmacology, DNA, Bacterial genetics, Drug Resistance, Bacterial, Helicobacter pylori genetics, Metronidazole pharmacology, Mutation, Tetracycline pharmacology, Anti-Infective Agents pharmacology, Helicobacter pylori drug effects
- Abstract
This study aims to determine the in vitro susceptibility of Helicobacter pylori to clarithromycin, metronidazole, amoxycillin and tetracycline, the four antibiotics commonly used in eradication therapies. These data are used to evaluate the efficacy of current empiric treatment of H. pylori infection in the Southern Region of Ireland. Culture is performed on gastric biopsy samples obtained from 147 consecutive patients undergoing gastroscopy for investigation of dyspepsia. Susceptibility testing to metronidazole, clarithromycin, amoxycillin and tetracycline is performed on the isolates by Etest. Isolates demonstrating clarithromycin resistance are subjected to polymerase chain reaction (PCR) amplification and nucleotide sequence analysis to identify the presence of point mutations in the peptidyltransferase region of the 23S rRNA gene previously associated with resistance to clarithromycin. Prevalence of H. pylori in the population studied was 31% (45 isolates). Antimicrobial resistance to metronidazole and clarithromycin was detected in nine (20%) and four (8.9%) of the isolates, respectively. A single isolate demonstrated co-resistance to metronidazole and clarithromycin (2.2%). No resistance was detected to either amoxycillin or tetracycline. The low level of resistance demonstrated among this group of isolates indicates that the empiric treatment currently in place in the Southern Region of Ireland is likely to be successful.
- Published
- 2006
- Full Text
- View/download PDF
32. Hepatitis C links hepatologists, nephrologists and transplant surgeons.
- Author
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Crosbie O and Alexander G
- Subjects
- Humans, Gastroenterology methods, Hepatitis C surgery, Kidney Transplantation, Liver Transplantation, Nephrology methods
- Published
- 1999
- Full Text
- View/download PDF
33. Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis.
- Author
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McCormick PA, Ooi H, and Crosbie O
- Subjects
- Aged, Female, Gastrointestinal Hemorrhage etiology, Humans, Antifibrinolytic Agents therapeutic use, Gastrointestinal Hemorrhage drug therapy, Liver Cirrhosis complications, Stomach Diseases complications, Tranexamic Acid therapeutic use, Vascular Diseases complications
- Abstract
Background: It is believed that severe portal hypertensive gastropathy probably accounts for most non-variceal bleeding episodes in patients with cirrhosis. Gastric antral vascular ectasia (GAVE) also occurs in these patients. It is not clear whether it is a variant of portal hypertensive gastropathy or a distinct condition., Patient: A patient, a 66 year od woman, with cirrhosis initially diagnosed as having portal hypertensive gastropathy and subsequently classified as GAVE is described. She required transfusion with a total of 130 units of packed red cells for gastrointestinal blood loss., Results: The bleeding did not respond to portal decompression with TIPS or beta blockers. Following treatment with oral tranexamic acid she has not required further blood transfusion over a period of 30 months., Conclusion: Tranexamic acid may be a useful treatment for refractory bleeding due to gastric antral vascular ectasia in patients with cirrhosis.
- Published
- 1998
- Full Text
- View/download PDF
34. Orthotopic liver transplantation for veno-occlusive disease complicating autologous bone marrow transplantation.
- Author
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Norris S, Crosbie O, McEntee G, Traynor O, Nolan N, McCann S, and Hegarty J
- Subjects
- Adult, Humans, Immunosuppressive Agents therapeutic use, Male, Thrombolytic Therapy, Bone Marrow Transplantation adverse effects, Hepatic Veno-Occlusive Disease etiology, Hepatic Veno-Occlusive Disease surgery, Liver Transplantation
- Abstract
Background: Veno-occlusive disease of the liver is a serious and often life-threatening complication after bone marrow transplantation. Although risk factors for the development of veno-occlusive disease have been postulated, there is no precise method for accurately identifying those patients who are at risk and for whom early intervention and treatment would have maximum potential benefit. Liver transplantation has been advocated as a treatment for veno-occlusive disease in selected patients., Methods: In this report, we describe a patient who underwent liver transplantation for life-threatening veno-occlusive disease after autologous bone marrow transplantation for acute lymphoblastic leukemia., Results: Liver engraftment was achieved, but the patient developed Pneumocystis pneumonia, which failed to respond to pentamidine. The patient died 6 months after liver transplantation., Conclusions: While acknowledging the limited experience of orthotropic liver transplantation in this patient population, we suggest its consideration as a feasible, potentially beneficial treatment option in patients with severe veno-occlusive disease after bone marrow transplantation.
- Published
- 1997
- Full Text
- View/download PDF
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