Persistence of hepatitis C virus in peripheral blood mononuclear cells of sustained viral responders to pegylated interferon and ribavirin therapy
ABSTRACT 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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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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ABSTRACT: Persistence of hepatitis C virus (HCV) in patients who cleared HCV is still debated. Occult HCV infection is described as the presence of detectable HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) of patients with undetectable plasma HCV-RNA by conventional PCR assays. We have assessed the persistence of HCV in 26 kidney-transplant patients, followed up for 10.5 years (range 2-16), after HCV elimination while on hemodialysis. If HCV really did persist, arising out of the loss of immune control caused by institution of the regimen of immunosuppressive drugs after kidney transplantation, HCV reactivation would have taken place. Their immunosuppression relied on calcineurin inhibitors (100%), and/or steroids (62%), and/or antimetabolites (94%). An induction therapy, given to 22 patients, relied on rabbit antithymocyte globulin (59%) or anti-IL2-receptor blockers (32%). All patients had undetectable HCV RNA as ascertained by several conventional tests. At the last follow-up, no residual HCV RNA was detected in the five liver biopsies, the 26 plasma, and in the 37 nonstimulated and 24 stimulated PBMCs tested with an ultrasensitive RT-PCR assay (detection limit, 2 IU/ml). No biochemical or virologic relapse was seen during follow-up. The absence of HCV relapse in formerly HCV-infected immunocompromised patients suggests the complete eradication of HCV after its elimination while on dialysis.Transplant International 12/2009; 23(6):594-601. DOI:10.1111/j.1432-2277.2009.01025.x · 3.16 Impact Factor
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ABSTRACT: Chronic hepatitis caused by Hepatitis C virus (HCV) is the main source of liver cirrhosis, hepatocellular carcinoma, and extra-hepatic diseases. After treatment-induced resolution of hepatitis C, the persistence of HCV RNA in serum and peripheral blood mononuclear cells (PBMCs) is often observed. An expression of the precursor of microRNA-155 (miR-155) called BIC can be the factor responsible for a course of HCV infection. Therefore, we assessed the relationship between BIC expression and HCV RNA status in sera and PBMCs samples of 64 hepatitis C patients treated with interferon alpha(IFN-alpha)+ribavirin. High expression of BIC in PBMCs was determined in 100% of patients that harbored HCV RNA in serum and PBMCs. Further, we found that 83% of PBMCs samples were BIC-positive in a group of patients that eliminated HCV RNA only from serum. The lowest expression of BIC was found in patients that eliminated HCV RNA from both serum and PBMCs.Acta virologica 01/2010; 54(1):75-8. DOI:10.4149/av_2010_01_75 · 1.04 Impact Factor