Persistence of Hepatitis C Virus in Peripheral Blood Mononuclear Cells of Sustained Viral Responders to Pegylated Interferon and Ribavirin Therapy

Department of Internal Medicine, Mayo Clinic, Arizona, Phoenix, AZ, USA.
Digestive Diseases and Sciences (Impact Factor: 2.61). 08/2008; 53(9):2564-8. DOI: 10.1007/s10620-008-0323-x
Source: PubMed


The aim of this paper was to assess the persistence of hepatitis C virus (HCV) among patients successfully treated with peginterferon and ribavirin. The persistence of viral RNA was evaluated in the serum and peripheral blood mononuclear cells (PBMCs) of 25 chronic hepatitis C patients with sustained viral response to peginterferon and ribavirin treatment up to 56 months after the completion of therapy. Viral RNA was detected in the peripheral blood mononuclear cell cultures of five patients (20%), but none had detectable serum HCV RNA. At present, the clinical relevance of this finding is unclear. It is possible that viral persistence and, specifically, the presence of HCV RNA in PBMCs may lead to HCV reactivation under special circumstances, such as immunosuppression.

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    • "In contrast, of the two individuals who developed CHC in their report and experienced a SVR with interferon-based therapy, one had persistent HCV genome in the liver [22]. There are only a few studies which applied high stringency methods for HCV-RNA detection and calibrated their assays as well as utilization of sequence analysis or nucleic acid hybridization probe amplification [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34]. Pham et al. [27] reported the original finding of occult hepatitis C infection (OCI) subsequently used these highly sensitive assays such as the hybridization to support their findings with assays capable of detecting HCV-RNA to ≤10 vge/mL (≤3 IU/mL) or ≤ 5 vge/ug (≤1.5 IU/ug) [26] [28]. "
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    ABSTRACT: Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990-2014). Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12-18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had "SVR" after 8-12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.
    Gastroenterology Research and Practice 07/2015; 2015:579147. DOI:10.1155/2015/579147 · 1.75 Impact Factor
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    • "According to our current findings we conclude that clinicians may be confident of the clearance of the virus as indicated by the absence of viral RNA in the serum at the EOT especially in the case of genotype 3 infection. A previous study on five geno 3 patients also showed clearance of virus after 56 months of treatment [17]. "
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    ABSTRACT: ABSTRACT: A recently discovered occult HCV entity reported by various investigators seems to be highly controversial. Especially, the clinical significance of these findings remains uncertain. For optimal outcome of antiviral therapy, investigation of occult HCV needs a broad-based probe in order to investigate the results of viral therapy and its host/viral interaction. The current study was aimed at determining the prevalence of occult HCV in peripheral blood lymphocytes of predominantly genotype 3 HCV-infected patients after completion of antiviral therapy and to investigate long term outcomes in the presence or absence of PBMC positivity. A total of 151 chronic, antiHCV and serum RNA-positive patients were enrolled in the study. Patients with a complete virological response at the end of treatment were screened for the presence of viral RNA in their PBMCs and were followed for up to one year for the presence of serum and PBMC viral genomic RNA. Out of 151 patients, 104 (70%) responded to the prescribed interferon treatment and showed viral-clearance from serum. These were screened for the presence of genomic RNA in their PBMCs. Sixteen samples were PBMC-positive for viral RNA at the end of treatment (EOT). All these patients had also cleared the virus from peripheral blood cells after the 6-12 month follow-up study. True occult hepatitis C virus does not exist in our cohort. Residual viremia at the EOT stage merely reflects a difference in viral kinetics in various compartments that remains a target of immune response even after the end of antiviral therapy and is eventually cleared out at the sustained viral response (SVR).
    Genetic Vaccines and Therapy 09/2011; 9(1):14. DOI:10.1186/1479-0556-9-14 · 2.10 Impact Factor
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    ABSTRACT: RESUMEN La infección crónica por virus de la hepatitis C (VHC) es un problema creciente a nivel mundial y constituye actualmente la causa más frecuente de trasplante hepático en Estados Unidos y Europa. El tratamiento actual consiste en la combinación de interferón pegilado y ribavirina, con respuesta viral sostenida en más del 50% de los pacientes. En la actualidad existen pruebas que sustentan el concepto de infección oculta o persistente por VHC en el hígado y las células mononucleares de sangre periférica en sujetos con resolución espontánea o farmacológica, definida convencionalmente como ausencia de viremia al menos seis meses después del tratamiento. Este fenómeno podría tener relevancia clínica, pues los sujetos con infección persistente pudieran estar en riesgo de recurrencia de la infección o de aparición de manifestaciones extrahepáticas que resultarían en un pronóstico desfavorable. Este artículo tiene como objetivo revisar la bibliografía actual al respecto de la persistencia viral y la infección oculta y sus potenciales implicaciones clínicas. Palabras clave: virus hepatitis C, enfermedad hepática, células mononucleares sanguíneas periféricas, infección oculta, hepatitis viral, viral persistente. ABSTRACT Chronic hepatitis C virus (HCV) infection is a common and growing problem in the world and is currently the most common reason for liver transplantation in the United States and Europe. Current therapy includes a combination of pegylated interferon and ribavirin, which has been shown to produce a sustained viral response in greater than 50% of patients. There is increasing evidence that supports the concept of occult or persistent HCV infection within hepatocytes and peripheral blood mononuclear cells (PBMCs) after spontaneous or therapy-induced sustained viral response defined as absence of detectable viremia at least 6 months after end of therapy. This may have some clinical importance as patients with persistent HCV may have increased risk of recurrence or extrahepatic manifestations of the infection that will alter their ultimate prognosis. Therefore, this article serves as a review of the current literature in HCV persistence in both hepatic and extrahepatic sites and their clinical implications.
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