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Gambato M, Pérez-Del-Pulgar S, Hedskog C, Svarovskia ES, Brainard D, Denning J, Curry MP, Charlton M, Caro-Pérez N, Londoño MC, Koutsoudakis G, Forns X. Hepatitis C Virus RNA Persists in Liver Explants of Most Patients Awaiting Liver Transplantation Treated With an Interferon-Free Regimen. Gastroenterology 2016; 151:633-636.e3. [PMID: 27373513 DOI: 10.1053/j.gastro.2016.06.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 06/15/2016] [Accepted: 06/17/2016] [Indexed: 01/09/2023]
Abstract
We assessed the presence of hepatitis C virus (HCV) RNA in liver explants from 39 patients awaiting liver transplantation who were treated with an interferon-free regimen and had undetectable serum HCV RNA at the time of liver transplantation. Interestingly, HCV RNA was detected in most liver explants (67%). Patients with HCV RNA-positive explants had received shorter courses of treatment, and HCV RNA was undetectable in serum for shorter periods before transplantation compared to patients with HCV RNA-negative explants (P = .014 and P = .013, respectively). Levels of HCV RNA in explants were significantly higher in patients with a relapse of HCV infection than patients who responded to treatment (P = .016), but most patients (85%) with residual HCV-RNA in the explant achieved a sustained virologic response after receiving their liver transplant.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Sofía Pérez-Del-Pulgar
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | | | | | | | | | | | | | - Noelia Caro-Pérez
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Maria Carlota Londoño
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - George Koutsoudakis
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain.
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Rossi LMG, Escobar-Gutierrez A, Rahal P. Advanced molecular surveillance of hepatitis C virus. Viruses 2015; 7:1153-88. [PMID: 25781918 PMCID: PMC4379565 DOI: 10.3390/v7031153] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 02/05/2015] [Accepted: 02/20/2015] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.
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Affiliation(s)
- Livia Maria Gonçalves Rossi
- Department of Biology, Institute of Bioscience, Language and Exact Science, Sao Paulo State University, Sao Jose do Rio Preto, SP 15054-000, Brazil.
| | | | - Paula Rahal
- Department of Biology, Institute of Bioscience, Language and Exact Science, Sao Paulo State University, Sao Jose do Rio Preto, SP 15054-000, Brazil.
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Preciado MV, Valva P, Escobar-Gutierrez A, Rahal P, Ruiz-Tovar K, Yamasaki L, Vazquez-Chacon C, Martinez-Guarneros A, Carpio-Pedroza JC, Fonseca-Coronado S, Cruz-Rivera M. Hepatitis C virus molecular evolution: Transmission, disease progression and antiviral therapy. World J Gastroenterol 2014; 20:15992-16013. [PMID: 25473152 PMCID: PMC4239486 DOI: 10.3748/wjg.v20.i43.15992] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 06/22/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.
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Veerapu NS, Park SH, Tully DC, Allen TM, Rehermann B. Trace amounts of sporadically reappearing HCV RNA can cause infection. J Clin Invest 2014; 124:3469-78. [PMID: 25003189 DOI: 10.1172/jci73104] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Accepted: 05/29/2014] [Indexed: 12/20/2022] Open
Abstract
Successful hepatitis C virus (HCV) treatment is defined as the absence of viremia 6 months after therapy cessation. We previously reported that trace amounts of HCV RNA, below the sensitivity of the standard clinical assay, can reappear sporadically in treatment responders. Here, we assessed the infectivity of this RNA and infused 3 chimpanzees sequentially at 9-week intervals with plasma or PBMCs from patients who tested positive for trace amounts of HCV RNA more than 6 months after completing pegylated IFN-α/ribavirin therapy. A fourth chimpanzee received HCV RNA-negative plasma and PBMCs from healthy blood donors. The 3 experimental chimpanzees, but not the control chimpanzee, generated HCV-specific T cell responses against nonstructural and structural HCV sequences 6-10 weeks after the first infusion of patient plasma and during subsequent infusions. In 1 chimpanzee, T cell responses declined, and this animal developed high-level viremia at week 27. Deep sequencing of HCV demonstrated transmission of a minor HCV variant from the first infusion donor that persisted in the chimpanzee for more than 6 months despite undetectable systemic viremia. Collectively, these results demonstrate that trace amounts of HCV RNA, which appear sporadically in successfully treated patients, can be infectious; furthermore, transmission can be masked in the recipient by an extended eclipse phase prior to establishing high-level viremia.
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Barreiro P, Fernandez-Montero JV, de Mendoza C, Labarga P, Soriano V. Towards hepatitis C eradication from the HIV-infected population. Antiviral Res 2014; 105:1-7. [PMID: 24534673 DOI: 10.1016/j.antiviral.2014.02.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2013] [Revised: 01/23/2014] [Accepted: 02/06/2014] [Indexed: 02/07/2023]
Abstract
Around 10-15% of the 35 million people living with HIV worldwide have chronic hepatitis C virus (HCV) infection and are prone to develop liver-related complications. Exposure to HCV is almost universal among injecting drug users and is on the rise among homosexual men. Response to peginterferon-ribavirin therapy is generally lower in coinfection compared to HCV monoinfection. For this reason, the advent of direct-acting antivirals (DAA) is eagerly awaited for this population. The results of trials using DAA in coinfection show that treatment response rates are similar to those obtained in HCV monoinfection. Thus, HIV should no longer be considered as a "special" population, as long as antiretroviral therapy is given and drug interactions are taken into account. Envisioning HCV eradication from the HIV population faces major challenges ahead, including identification of the large number of undiagnosed individuals, and ensuring wide access to the best but often expensive HCV medications. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication".
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Affiliation(s)
- Pablo Barreiro
- Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain
| | | | - Carmen de Mendoza
- Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; Department of Internal Medicine, Puerta de Hierro Research Institute & Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Pablo Labarga
- Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain
| | - Vincent Soriano
- Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
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Treatment of Hepatitis C in HIV Patients in the New Era of Direct-Acting Antivirals. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/s11901-013-0179-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Soriano V, Vispo E, de Mendoza C, Labarga P, Plaza Z, Fernandez-Montero JV, Poveda E, Treviño A, Barreiro P. Very late relapse after discontinuation of antiviral therapy for chronic hepatitis C. Antivir Ther 2013; 18:1033-5. [PMID: 23804629 DOI: 10.3851/imp2659] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2013] [Indexed: 10/26/2022]
Abstract
Serum HCV RNA rebound beyond 24 weeks after completing hepatitis C therapy has been rarely reported. From 744 patients treated for chronic hepatitis C at our institution, 4 became HCV-RNA-positive again between weeks 36 and 48 post-treatment. Epidemiological and phylogenetic analyses supported very late HCV relapse instead of re-infection in two of them. This observation may have important implications in the pathogenesis and therapeutics of HCV infection.
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Affiliation(s)
- Vincent Soriano
- Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
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