Hepatitis C virus and the immune system: a concise review

Gremion, Christel; Cerny, Andreas

doi:10.1002/rmv.466

Cited by 88 publications

(65 citation statements)

References 170 publications

(178 reference statements)

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“…Herein, we describe that RFA exerted immunomodulatory effects on distinct effector immune cells in metastatic cancer patients, in particular in the redistribution of circulating T cells; similar event was observed in pancreatic cancer patients undergoing RFA (data not shown). No modulation effect seems to occur in HCC patients: the chronic condition underlying tumor development could account for an overall weakening of NK and T cell-mediated immunity (34,35). However, it is noteworthy that in all the liver cancer patients studied a significant and stable decrease of circulating CD62L + T cells of both memory and naïve subsets was observed suggesting the migration of these cells into the tissues.…”

Section: Discussionmentioning

confidence: 96%

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

et al. 2008

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Abstract. Radiofrequency tumor ablation (RFA) is a therapeutic modality for liver cancer patients inducing localized tumor necrosis with maximal preservation of normal liver parenchyma. We investigated the immunomodulatory effects exerted by RFA treatment in liver cancer patients with metastatic liver lesions (13 patients) or hepatocellular carcinoma (HCC) (4 patients). Analysis of lymphocyte subsets by flow cytometry revealed that after RFA, CD3 + T cells, in particular CD4 + , were decreased in metastatic cancer patients, while no change was observed in HCC patients. Moreover, RFA induced trafficking of naïve and memory CD62L + T cells from circulation to tissues. When characterizing the function of T cells, proliferative response to PHA was strongly increased after 48 h from RFA in metastatic cancer patients. Furthermore, T cells produced IFN-γ in response to the tumor associated MUC1 antigen. In contrast, humoral immune responses against tumor antigens such as MUC1 and HCV proteins were unaffected by RFA treatment, although increase of circulating B cells was observed only in metastatic cancer patients. These results indicate that RFA application can exert an activating effect on the immune system in metastatic cancer patients, favouring trafficking of lymphocyte subsets and enhancing tumor antigen specific cellular immune responses.

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Section: Discussionmentioning

confidence: 96%

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

et al. 2008

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“…In individuals infected with HCV, the persistence of the virus can be attributed the large inoculum and the high rate of viral replication, which allow the virus to evade the host immune response [4,23]. There is controversy over whether the sequence of nucleotides is directly associated with more intense hepatic lesions [6,24,25].…”

Section: Life Cycle and Pathogenicity Of Hcvmentioning

confidence: 99%

“…In HCV infection, the genetic constitution and immune 'status' of the host are important factors in the persistence and progression of the virus [23,93], since they influence antigen recognition and presentation, as well as the type of Th response [94].…”

Section: Host Factors Associated With the Persistence And Progressionmentioning

confidence: 99%

“…The production of new viruses is counterbalanced by the destruction of infected cells through tissue apoptosis or degradation in peripheral blood, since the half-life of the virus in peripheral blood is approximately 2.7 hours [7]. Experimental studies have shown that NS3 and NS5 proteins induce apoptosis in infected hepatocytes [22].In individuals infected with HCV, the persistence of the virus can be attributed the large inoculum and the high rate of viral replication, which allow the virus to evade the host immune response [4,23]. There is controversy over whether the sequence of nucleotides is directly associated with more intense hepatic lesions [6,24,25].…”

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confidence: 99%

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Pathogenesis of hepatitis C: HCV consensus 2007

Viso¹

2007

Braz J Infect Dis

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The chronic hepatitis C virus (HCV) infects approximately 130 million people worldwide [1]. It is estimated that approximately 15% of HCV-infected individuals eliminate the virus spontaneously, that 25% develop a mild form of the disease, and that 60% develop the chronic progressive form [2]. The elimination or persistence of HCV infection depends on the balance between the effectiveness, specificity and rapidity of the innate and adaptive immune responses, as well as on the HCV replication rate [3]. Persistence of HCV can also be caused by infection at privileged (extrahepatic) sites, viral inhibition of antigen presentation, selective immune suppression, negative regulation of HCV gene expression, viral mutations, immune exhaustion of T cells and the incomplete differentiation of memory T cells [4,5].Fibrosis is the principal complication of chronic hepatitis C, and it is estimated that 20% of patients develop cirrhosis over a period of 10, 20 or 30 years [2,6]. The progression of fibrosis increases morbidity and mortality in chronic hepatitis C [7], since it can lead to death due to complications caused by cirrhosis or hepatocarcinoma [2].Various studies have associated the progression of fibrosis in hepatitis C with diverse factors such as: the kinetics and pathogenicity of HCV; host-HCV interaction; intrinsic host factors such as demographic profile, body mass index and diabetes mellitus; host exposure to external factors; and the form of HCV acquisition. Life Cycle and Pathogenicity of HCVBelonging to the Flaviviridae family, HCV is a small enveloped virus [8]. Its genome consists of one RNA molecule that is composed of two terminal regions, 5'-and 3'-untranslated regions, and between these there is a single open reading frame that encodes a polyprotein with approximately 3000 amino acids. This polyprotein cleaves at the N-terminal side of three structural proteins, the nucleocapsid (core), envelope 1 (E1) and envelope 2 (E2), all of which are involved in the architectural organization of HCV. At the carboxylterminal side, the polyprotein cleaves to six nonstructural proteins, NS2, NS3, NS4 (NS4A and NS4B), NS5 (NS5A and NS5B) and NS6, which are responsible for the life cycle of the virus [9].After entering a susceptible host, HCV invades, infects and replicates within the blood stream, repeating the process in various tissues, as well as in peripheral B and T lymphocytes, as it proceeds to the liver by tropism, passing through various tissues such as those of the pancreas, thyroid, adrenal glands, spleen and bone marrow [10][11][12]. Since HCV can also directly infect the lymphatic tissue, its stimulation can lead to the development of B-cell lymphomas [13]. It is known that the liver is the principal site of HCV replication, and various studies have shown that this virus infects approximately 10% of hepatic cells [5]. Infection with HCV at extrahepatic sites can promote the appearance of HCV variants [14,15], thereby decreasing the chance that the immune system will recognize the virus.To enter the host ...

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“…About 55 to 85% of HCV patients do not clear the virus themselves and develop chronic Hep-C infection [2]. The progression to chronic-stage HCV infection is a result of weak immune response against HCV (reviewed in [6]). Currently, the standard protocol for the treatment of Hep-C involves two antiviral drugs, Interferon-α (IFN) and ribavirin (RBV), given in combination [7,8].…”

Section: Introductionmentioning

confidence: 99%

Evaluating treatment of hepatitis C for hemolytic anemia management

DebRoy

Kribs-Zaleta

Mubayi

et al. 2010

Mathematical Biosciences

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The combination therapy of antiviral peg-interferon and ribavirin has evolved as one of the better treatments for Hepatitis-C. In spite of its success in controlling Hepatitis-C infection, it has also been associated with treatment-related adverse side effects. The most common and life threatening among them is hemolytic anemia, necessitating dose reduction or therapy cessation. The presence of this side effect leads to a tradeoff between continuing the treatment and exacerbating the side-effects versus decreasing dosage to relieve severe side-effects while allowing the disease to progress. The drug epoietin (epoetin) is often administered to stimulate the production of red blood cells (RBC) in the bone marrow, in order to allow treatment without anemia. This paper uses mathematical models to study the effect of combination therapy in light of * Corresponding author anemia. In order to achieve this we introduce RBC concentration and amount of drug in the body as state variables in the usual immunological virus infection model. Analysis of this model provides a quantification of the amount of drug a body can tolerate without succumbing to hemolytic anemia. Indirect estimation of parameters allow us to calculate the necessary increment in RBC production to be ≥ 2.3 times the patient's original RBC production rate to sustain the entire course of treatment without encountering anemia in a sensitive patient.

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Hepatitis C virus and the immune system: a concise review

Cited by 88 publications

References 170 publications

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

Pathogenesis of hepatitis C: HCV consensus 2007

Evaluating treatment of hepatitis C for hemolytic anemia management

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