|
1
|
Ridruejo E, Pereson MJ, Flichman DM, Di Lello FA. Hepatitis C virus treatment failure: Clinical utility for testing resistance-associated substitutions. World J Hepatol 2021; 13:1069-1078. [PMID: 34630875 PMCID: PMC8473504 DOI: 10.4254/wjh.v13.i9.1069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/12/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
Collapse
Affiliation(s)
- Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Ciudad Autónoma de Buenos Aires C1425AS, Unspecified, Argentina
| | - Matías Javier Pereson
- Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina
| | - Diego M Flichman
- Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida (INBIRS), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina
| | - Federico Alejandro Di Lello
- Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina.
| |
Collapse
|
|
2
|
Kumar N, Prabhu SS, Monga I, Banerjee I. Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis. Meta Gene 2021. [DOI: 10.1016/j.mgene.2021.100909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
3
|
Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection. PLoS One 2015; 10:e0143492. [PMID: 26640956 PMCID: PMC4671604 DOI: 10.1371/journal.pone.0143492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 10/06/2015] [Indexed: 11/30/2022] Open
Abstract
Background Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. Patients and Methods This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. Results Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. Conclusions No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. Trial Registration ClinicalTrials.gov NCT01529073
Collapse
|
|
4
|
Monje-Agudo P, Castro-Iglesias A, Rivero-Juárez A, Martínez-Marcos F, Ortega-González E, Real LM, Pernas B, Merchante N, Cid P, Macías J, Merino MD, Rivero A, Mena A, Neukam K, Pineda JA. Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin. Eur J Clin Microbiol Infect Dis 2015; 34:1929-36. [PMID: 26155784 DOI: 10.1007/s10096-015-2434-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2015] [Accepted: 06/22/2015] [Indexed: 12/18/2022]
Abstract
It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.
Collapse
Affiliation(s)
- P Monje-Agudo
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain
| | - A Castro-Iglesias
- Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidad de A Coruña, 15006, A Coruña, Spain
| | - A Rivero-Juárez
- Unit of Infectious Diseases, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Avda Menéndez Pidal s/n, 14004, Córdoba, Spain
| | - F Martínez-Marcos
- Unit of Infectious Diseases, Complejo Hospitalario de Huelva, Ronda Exterior Norte s/n, 21005, Huelva, Spain
| | - E Ortega-González
- Unit of Infectious Diseases, Consorcio Hospital General Universitario de Valencia, Av. Tres Cruces s/n, 46014, Valencia, Spain
| | - L M Real
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain
| | - B Pernas
- Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidad de A Coruña, 15006, A Coruña, Spain
| | - N Merchante
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain
| | - P Cid
- Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidad de A Coruña, 15006, A Coruña, Spain
| | - J Macías
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain
| | - M D Merino
- Unit of Infectious Diseases, Complejo Hospitalario de Huelva, Ronda Exterior Norte s/n, 21005, Huelva, Spain
| | - A Rivero
- Unit of Infectious Diseases, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Avda Menéndez Pidal s/n, 14004, Córdoba, Spain
| | - A Mena
- Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidad de A Coruña, 15006, A Coruña, Spain
| | - K Neukam
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain.
| | - J A Pineda
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Avda de Bellavista s/n, 41014, Sevilla, Spain
| |
Collapse
|
|
5
|
Neukam K, Munteanu DI, Rivero-Juárez A, Lutz T, Fehr J, Mandorfer M, Bhagani S, López-Cortés LF, Haberl A, Stoeckle M, Márquez M, Scholten S, de los Santos-Gil I, Mauss S, Rivero A, Collado A, Delgado M, Rockstroh JK, Pineda JA. Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy. PLoS One 2015; 10:e0125080. [PMID: 25923540 PMCID: PMC4414348 DOI: 10.1371/journal.pone.0125080] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 03/20/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIMS Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. METHODS In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. RESULTS Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. CONCLUSION The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.
Collapse
Affiliation(s)
- Karin Neukam
- Unit of Infectious Diseases and Microbiology, Valme University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
| | - Daniela I. Munteanu
- Department of Medicine I, Bonn University Hospital, Bonn-Venusberg, Germany
- Matei Bals National Institute of Infectious Diseases, Bucharest, Romania
| | - Antonio Rivero-Juárez
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Reina Sofía University Hospital, Maimónides Institute of Biomedical Investigation of Cordoba (IMIBIC), Cordoba, Spain
| | - Thomas Lutz
- Infektiologikum Frankfurt, Frankfurt/Main, Germany
| | - Jan Fehr
- Division of Infectious Diseases & Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna and Vienna HIV & Liver Study Group, Vienna, Austria
| | - Sanjay Bhagani
- Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Luis F. López-Cortés
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
| | - Annette Haberl
- Department of Medicine II, Frankfurt University Hospital, Frankfurt/Main, Germany
| | - Marcel Stoeckle
- Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Manuel Márquez
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Virgen de la Victoria University Hospital, Malaga, Spain
| | | | - Ignacio de los Santos-Gil
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Infectious Diseases Unit, La Princesa University Hospital, Madrid, Spain
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Dusseldorf, Germany
| | - Antonio Rivero
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
- Unit of Infectious Diseases, Reina Sofía University Hospital, Maimónides Institute of Biomedical Investigation of Cordoba (IMIBIC), Cordoba, Spain
| | - Antonio Collado
- Infectious Diseases Unit, Torrecardenas University Hospital, Almeria, Spain
| | - Marcial Delgado
- Unit of Infectious Diseases, Carlos Haya Regional University Hospital, Malaga, Spain
| | | | - Juan A. Pineda
- Unit of Infectious Diseases and Microbiology, Valme University Hospital and Seville Institute of Biomedicine (IBiS), Seville, Spain
- RIS-HEP07 Study Group of the Spanish AIDS Research Network
| |
Collapse
|
|
6
|
Macías J, Neukam K, Merchante N, Pineda JA. Latest pharmacotherapy options for treating hepatitis C in HIV-infected patients. Expert Opin Pharmacother 2014; 15:1837-48. [PMID: 25085577 DOI: 10.1517/14656566.2014.934810] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV)/HIV-coinfected patients are at an increased risk of progression of liver disease. Consequently, they benefit most from sustained virological response (SVR) to treatment against HCV. However, SVR rates to pegylated IFN plus ribavirin are disappointingly low in HIV/HCV coinfection. Nevertheless, therapy against HCV is rapidly changing due to the advent of directly acting antiviral drugs against HCV (DAA). Now, high SVR rates can be obtained in HIV/HCV coinfection with DAA regimens. AREAS COVERED Data on DAAs in advanced stages of development in HIV/HCV coinfection, those that have entered Phase III clinical trials in this particular subset, are summarized. A search of clintrials.gov was done to identify DAAs entering Phase III trials that included HIV/HCV-coinfected patients. EXPERT OPINION HCV cure is possible in a high proportion of HIV-coinfected patients with currently available DAA. Caveats of first-generation DAAs are mostly solved by next-generation DAAs. Thus, all-oral regimens under development may be close to the ideal HCV therapy for HIV-coinfected patients. However, the elevated cost of newer DAAs can limit their access.
Collapse
Affiliation(s)
- Juan Macías
- Hospital Universitario de Valme, Unit of Infectious Diseases and Microbiology , Avda. de Bellavista. 41014 Sevilla , Spain +34 955015684 ; +34 955315795 ;
| | | | | | | |
Collapse
|
|
7
|
Corchado S, López-Cortés LF, Rivero-Juárez A, Torres-Cornejo A, Rivero A, Márquez-Coello M, Girón-González JA. Liver fibrosis, host genetic and hepatitis C virus related parameters as predictive factors of response to therapy against hepatitis C virus in HIV/HCV coinfected patients. PLoS One 2014; 9:e101760. [PMID: 25013899 PMCID: PMC4094489 DOI: 10.1371/journal.pone.0101760] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 06/11/2014] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism). PATIENTS AND METHODS A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, -238 TNF-α and -592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count. RESULTS Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600,000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600,000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of -238 TNF-α genotype GG was detected in patients with significant liver fibrosis. CONCLUSIONS In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a -238 TNF-α polymorphism in these patients.
Collapse
Affiliation(s)
- Sara Corchado
- Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Luis F. López-Cortés
- Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
| | - Antonio Rivero-Juárez
- Maimonides Institute for Research in Biomedicine of Cordoba/Reina Sofia University Hospital, Córdoba, Spain
| | - Almudena Torres-Cornejo
- Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
| | - Antonio Rivero
- Maimonides Institute for Research in Biomedicine of Cordoba/Reina Sofia University Hospital, Córdoba, Spain
| | | | | |
Collapse
|
|
8
|
Real LM, Neukam K, Herrero R, Guardiola JM, Reiberger T, Rivero-Juarez A, Salazar J, Mandorfer M, Merino D, Soriano V, Rivero A, Macías J, Pineda JA, Caruz A. IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians. PLoS One 2014; 9:e95515. [PMID: 24748394 PMCID: PMC3991683 DOI: 10.1371/journal.pone.0095515] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 03/27/2014] [Indexed: 01/30/2023] Open
Abstract
Objectives The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with that of rs12979860. Methods 272 Caucasian HCV-1/4-infected patients who completed a course of pegIFN/RBV were genotyped for both rs12979860 and ss469415590 markers. Logistic regression models including factors with univariate association with SVR and each genetic marker were elaborated. The area under the receiver operating-characteristic curve (AUROC) was calculated for each model and both were compared. Results Both markers were in LD (r2 = 0.82). For rs12979860, 66 (64.0%) CC versus 56 (33.1%) T allele carriers achieved SVR (Adjusted OR = 4.156, 95%CI = 2.388–7.232, p = 4.647×10−7). For ss469415590, 66 (66.0%) TT/TT versus 56 (32.5%) –G allele carriers (Adjusted OR = 4.783, 95%CI = 2.714–8.428, p = 6.153×10−8) achieved SVR. The AUROC of the model including rs12979860 was 0.742 (95%CI = 0.672–0.813) and of that based on ss469415590 was 0.756 (95%CI = 0.687–0.826) (p = 0.780). Conclusions The ss469415590 variant shows an equivalent performance to predict SVR to pegIFN/RBV than the rs2979860 in Caucasian HCV-1/4-infected patients.
Collapse
Affiliation(s)
- Luis M. Real
- Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain
- Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain
| | - Karin Neukam
- Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain
- Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain
| | - Rocío Herrero
- Unidad de Inmunogenética, Universidad de Jaén, Jaén, Spain
| | - Josep M. Guardiola
- Servicio de Medicina Interna. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Vienna, Austria
| | - Antonio Rivero-Juarez
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), Córdoba, Spain
| | - Juliana Salazar
- Servicio de Medicina Interna. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Vienna, Austria
| | - Dolores Merino
- Unidad de Enfermedades Infecciosas. Hospital Juan Ramón Jiménez, Huelva, Spain
| | - Vicente Soriano
- Departamento de Enfermedades Infecciosas. Hospital Carlos III, Madrid, Spain
| | - Antonio Rivero
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), Córdoba, Spain
| | - Juan Macías
- Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain
- Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain
| | - Juan A. Pineda
- Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain
- Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain
| | - Antonio Caruz
- Unidad de Inmunogenética, Universidad de Jaén, Jaén, Spain
- * E-mail:
| |
Collapse
|
|
9
|
Liu T, Sha K, Yang L, Wang Y, Zhang L, Liu X, Yang F. IL-28B polymorphisms correlated with treatment response in HCV-4 mono-infected patients: a meta-analysis. PLoS One 2014; 9:e91316. [PMID: 24642705 PMCID: PMC3958354 DOI: 10.1371/journal.pone.0091316] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Accepted: 02/07/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The role of interleukin 28B (IL-28B) polymorphisms played in hepatitis C virus (HCV) infection has been gradually explicit, especially in HCV genotype 1, 2 and 3. However, no confirmative conclusion was acquired in genotype 4 HCV patients. Thus we conducted this meta-analysis. METHODS We searched the commonly used databases both in English and Chinese. Meta-analysis was performed in fixed/random effects models using STATA 12.0 or R software. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS In total, 11 studies were included in this meta-analysis, encompassing 1284 patients who were mono-infected with HCV-4 and received Peg-interferon (Peg-IFN) plus Ribavirin (Rbv). Around 53.0% patients would achieve sustained virologic response (SVR), 36.6% achieve rapid virologic response (RVR) and 62.4% achieve end of treatment response (ETR). Egyptian patients had a higher rate achieving SVR than non-Egyptian patients (56.3% vs. 47.8%). IL-28B rs12979860 CC genotype not only favored SVR (OR = 3.95, 95%CI = 3.03-5.16), regardless of citizenship, but also favored RVR (OR = 3.82, 95%CI = 2.46-5.95) and ETR (OR = 4.22, 95%CI = 2.81-6.34). IL-28B rs8099917 genotype TT also correlated with SVR (OR = 3.41, 95%CI = 1.92-6.07), but might not with RVR. IL-28B rs12980275 might still correlate with SVR, but warrant more studies to validate. CONCLUSIONS The favorable IL-28B rs12979860 genotype is a statistically significant predictor of SVR, RVR and ETR in HCV-4 monoinfected patients treated with Peg-IFN plus Rbv. Rs8099917 might predict SVR but not RVR. Egyptian HCV-4 patients would achieve better outcomes than non-Egyptian patients when treated with standard care.
Collapse
Affiliation(s)
- Tonggang Liu
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Kaihui Sha
- Binzhou Medical University School of Nursing, Binzhou, Shandong, China
| | - Luhua Yang
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Yun Wang
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Liguo Zhang
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Xianxian Liu
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Fang Yang
- Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China
| |
Collapse
|
|
10
|
Kawaguchi-Suzuki M, Frye RF. The role of pharmacogenetics in the treatment of chronic hepatitis C infection. Pharmacotherapy 2014; 34:185-201. [PMID: 24114761 DOI: 10.1002/phar.1349] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) chronically infects 170 million people worldwide. Until recently, combination therapy with peginterferon-α (pegIFN) and ribavirin (RBV) has been the standard of care. However, for many patients, especially those infected with the most common HCV genotype 1 (HCV-1), this treatment has resulted in unsatisfactory treatment response rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. Genetic variation in the interleukin 28B (IL28B) gene is the major determinant of treatment response, a finding that has been replicated in multiple independent cohorts. This review focuses on the association between pharmacogenetics and conventional pegIFN/RBV therapy in patients infected with HCV non-genotype 1; patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. We also review the pharmacogenetic data for boceprevir and telaprevir triple therapy in patients with HCV-1 infection, as well as viral genomic polymorphisms and genetic variants that may protect against anemia. Pharmacogenetic information offers a personalized medicine approach to help clinicians and patients make better informed decisions to maximize response and minimize toxicity for the treatment of chronic HCV infection.
Collapse
Affiliation(s)
- Marina Kawaguchi-Suzuki
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida
| | | |
Collapse
|
|
11
|
Di Lello FA, Neukam K, Parra-Sanchez M, Plaza Z, Soriano V, Cifuentes C, Mira JA, Poveda E, Pineda JA. Hepatitis C virus genotype 4 in Southern and Central Spain does not originate from recent foreign migration waves. J Med Virol 2013; 85:1734-40. [PMID: 23861220 DOI: 10.1002/jmv.23657] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2013] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus genotype 4 (HCV-4) is highly prevalent in Spain, but the information on the molecular characterization of HCV-4 in this region is scarce. Due to this, the molecular characteristics and the evolution of HCV-4 infection in Seville were analyzed (Southern Spain) and compared them with samples from Madrid. HCV genotype was determined by LIPA 2.0 assay and confirmed by sequence analysis of NS5B. Phylogenetic tree was estimated by MEGA 5.10. Bayesian coalescent-based methods were used to estimate the substitution rate and the age of the most recent common ancestor (MRCA). In the phylogenetic analysis of 50 NS5B HCV-4 from Seville and 11 from Madrid, 2 clusters were distinguished: The first cluster (HCV-4a) included 48% of the sequences from Seville and 9% of sequences from Madrid. The second cluster included the remaining sequences belonging to HCV-4d. The mean estimated substitution rate was 2.39 × 10(-3) for HCV-4a and 1.81 × 10(-3) for HCV-4d for Seville and 2.32 × 10(-3) for HCV-4d from Madrid. The date for MRCA was estimated to be around 1981-1984 for HCV-4 from Seville. The dates for MRCA were dated before the recent flow of immigration in Spain. Therefore, the results presented in this study argues against the possibility of a foreign introduction of the HCV-4 from other regions with high prevalence, at least during the last two, decades in which there was a great flow of immigrants. Additionally, an unusual high prevalence of subtype 4a was observed in Seville.
Collapse
Affiliation(s)
- Federico A Di Lello
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain
| | | | | | | | | | | | | | | | | |
Collapse
|
|
12
|
Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, García-Álvarez M, Resino S. Meta-analysis: implications of interleukin-28B polymorphisms in spontaneous and treatment-related clearance for patients with hepatitis C. BMC Med 2013; 11:6. [PMID: 23298311 PMCID: PMC3570369 DOI: 10.1186/1741-7015-11-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 01/08/2013] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Since 2009, several studies have identified single-nucleotide polymorphisms (SNPs) near the gene encoding for interleukin (IL)-28 (IL28B) that are strongly associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Because this large amount of data includes some inconsistencies, we consider assessment of the global estimate for each SNP to be essential. METHODS Relevant studies assessing IL28B polymorphisms associated with sustained virologic response (SVR) and spontaneous clearance (SC) were identified from a literature search of PubMed up to 9 July, 2012. Studies were eligible studies if they included patients infected with HCV or HCV/HIV, or assessed any SNP located within or near the IL28B gene, SVR data available under standard treatment, and/or SC data in patients with acute HCV infection. Pooled odds ratios were estimated by fixed or random effects models when appropriate. Variables such as HCV genotype, ethnicity, and type of co-infection were studied. RESULTS Of 282 screened studies, 67 were selected for SVR and 10 for SC. In total, 20,163 patients were studied for SVR and 3,554 for SC. For SVR, we found that all SNPs showed strong associations in patients with HCV genotypes 1 and 4, whereas the pooled ORs were almost three times lower for genotypes 2 and 3 (rs12979860 and rs8099917). Regarding ethnicity, the SNP most associated with SVR was rs12979860 in white patients, whereas in East Asians it seemed to be rs8099917. The most studied SNP (rs12979860) showed similar results for patients co-infected with HCV/HIV, as for those infected with HCV only. Finally, rs12979860 and rs8099917 both appeared to be associated with SC. CONCLUSIONS IL28B polymorphisms influence both the outcome of interferon treatment and the natural clearance of HCV. However we did not identify a universal predictor SNP, as the best genetic markers differed depending on patient ethnicity, genotype, and type of infection. Nevertheless, our results may be useful for more precise treatment decision-making.
Collapse
Affiliation(s)
- María A Jiménez-Sousa
- Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
| | - María Guzmán-Fulgencio
- Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
| | - Mónica García-Álvarez
- Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
| | - Salvador Resino
- Unit of HIV/Hepatitis Coinfection, National Center for Microbiology, Health Institute Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
| |
Collapse
|