Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients

Akiyama, Hideki; Yoshinaga, H; Tanaka, Takeshi; Hiruma, Kiyoshi; Tanikawa, S; Sakamaki, Hisashi; Onozawa, Y; Wakita, Takaji; Kohara, Michinori

doi:10.1038/sj.bmt.1700996

Cited by 32 publications

(22 citation statements)

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“…Conceivable targets of the Ca 2ϩ /calcineurin pathway include the NFAT-driven, anergy-associated genes (50) and the MAP kinase phosphatases, which inhibit JNK activity by dephosphorylation (31,46). Notably, treatment with cyclosporine A has been demonstrated to reduce the viral load during anti-HCV therapy (1,36). Whereas cyclosporine A is normally used for the suppression of allograft reactions, its inhibitory effects on NFAT can also prevent the acquisition of an anergic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses

Sundström

Ota

Dimberg

et al. 2005

J Virol

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Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses

Sundström

Ota

Dimberg

et al. 2005

J Virol

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“…Scattered reports have noted the effectiveness of CsA treatment in patients with HCV. [19][20][21] Notably, it was recently reported that combination therapy of IFN-␣ and CsA was more effective in HCV than IFN-␣ monotherapy. 22 In the setting of liver transplantation for hepatitis C, during which CsA is given as an immunosuppressant, there have been conflicting reports regarding the efficacy of CsA.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A Suppresses Replication of Hepatitis C Virus Genome in Cultured Hepatocytes

et al. 2003

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Persistent infection of hepatitis C virus (HCV) is a major cause of liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Searching for a substance with anti-HCV potential, we examined the effects of a variety of compounds on HCV replication using a HCV subgenomic replicon cell culture system. Consequently, the immunosuppressant cyclosporin A (CsA) was found to have a suppressive effect on the HCV replicon RNA level and HCV protein expression in these cells. CsA also inhibited multiplication of the HCV genome in a cultured human hepatocyte cell line infected with HCV using HCV-positive plasma. This anti-HCV activity of CsA appeared to be independent of its immunosuppressive function. In conclusion, our results suggest that CsA may represent a new approach for the development of anti-HCV therapy. (HEPATOLOGY 2003;38:1282-1288 P ersistent infection with the hepatitis C virus (HCV), identified as the major causative agent of non-A, non-B hepatitis, 1,2 has been closely related to liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. 3 The development of these liver diseases from HCV carriers, an estimated 170 million people throughout the world, is a major public health problem. Effective anti-HCV therapy has been restricted mainly to therapy with interferon (IFN) and a combination of IFN and ribavirin. However, because the virus is not eliminated from approximately one half of HCVinfected patients treated with these agents, 4 alternative approaches to the treatment of HCV infection are needed.Recently, an HCV subgenomic replicon cell culture system has been established in which an HCV subgenomic replicon autonomously replicated in Huh-7 cells (HCV replicon cells). 5 This replicon is composed of the HCV 5Ј-untranslated region containing an internal ribosomal entry site, the neomycin phosphotransferase gene, the encephalomyocarditis virus internal ribosomal entry site, HCV nonstructural proteins (NS) 3 through NS5B; and the HCV 3Ј-untranslated region (Fig. 1A). This system provides a unique tool for studying the mechanisms of HCV replication and screening as well as evaluating anti-HCV compounds. Taking advantage of this feature, we examined the effects of various types of compounds on the replication of HCV using HCV replicon cells established in our laboratory 6 (Miyanari et al., manuscript accepted for publication). Consequently, we found that a well-known immunosuppressant, cyclosporin A (CsA), 7 had a strong suppressive effect on HCV replication in these cells. Moreover, we found suppressive activity of CsA for multiplication of the HCV genome in cultured human hepatocytes infected with HCV. The mechanism of the anti-HCV activity of CsA was also studied. Materials and MethodsCell Culture. Huh-7 and MH-14 cells, HCV replicon cells, were cultured in Dulbecco's modified Eagle medium with 10% fetal bovine serum. PH5CH8 cells were cultured in a 1:1 mixture of Dulbecco's modified Eagle medium and F12 medium supplemented with 100 ng/mL epidermal gro...

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“…4 Projections about these risks have been based on case reports and studies of patients with a survival rate of about 10 years, some of them significantly differing in regard to the importance of the HCV in the post-BMT. [4][5][6][7] Today, with a worldwide BMT history of more than 30 years, hepatitis C in longterm survivors requires special attention. The aims of this study were: to determine the prevalence of the HCV antibody in patients who are alive 10 years or more after BMT at the Hospital de Clı´nicas of the Federal University of Parana´(HC-UFPR), to define the annual progression rate of hepatic fibrosis in those patients, and to detect liver cirrhosis among patients who are positive for the HCV antibody.…”

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confidence: 99%

Hepatitis C virus in long-term bone marrow transplant survivors

Ivantes

Amarante

Ioshii

et al. 2004

Bone Marrow Transplant

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Summary:The hepatitis C virus (HCV) infection may change the outcome of patients undergoing stem cell transplantation. This study aimed at determining the prevalence of the HCV antibody in patients who were alive 10 or more years after BMT, defining the annual progression rate of hepatic fibrosis in those patients, and identifying cases of cirrhosis among those who were positive for HCV antibody. Between 1979 and 1990, 259 patients had a bone marrow transplant, and 91 were alive in March 2000. Of those, 80 were included in the study after having been scanned for serum HCV antibodies. A total of 39 were positive (48.8%), one was indeterminate and 40 were negative (50%). The patients who were HCV positive or undetermined were called for a medical appointment and 22 (55%) attended. A total of 16 patients (72.7%) were male, the mean age was 37.879.2 years and all of them had had an allogeneic transplant. Of the 22 patients studied, 12 (54.5%) agreed to have a liver biopsy. Hepatic fibrosis was diagnosed in 10 patients. The hepatic fibrosis annual progression rate was 0.156 UF/year. Among the anti-HCV-positive patients assessed, three (13.6%) already had cirrhosis.

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Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients

Cited by 32 publications

References 1 publication

Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses

Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses

Cyclosporin A Suppresses Replication of Hepatitis C Virus Genome in Cultured Hepatocytes

Hepatitis C virus in long-term bone marrow transplant survivors

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