Real-Time PCR Assays for Hepatitis C Virus (HCV) RNA Quantitation Are Adequate for Clinical Management of Patients with Chronic HCV Infection

ABSTRACT Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.

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Replication of Hepatitis C Virus (HCV) RNA in Mouse Embryonic Fibroblasts: Protein Kinase R (PKR)-Dependent and PKR-Independent Mechanisms for Controlling HCV RNA Replication and Mediating Interferon Activities

Journal of Virology ◽

10.1128/jvi.00586-06 ◽

2006 ◽

Vol 80 (15) ◽

pp. 7364-7374 ◽

Cited By ~ 78

Author(s):

Kyung-Soo Chang ◽

Zhaohui Cai ◽

Chen Zhang ◽

Ganes C. Sen ◽

Bryan R. G. Williams ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Rna Replication ◽

Hcv Infection ◽

Hcv Rna ◽

Protein Kinase R ◽

Mouse Embryonic Fibroblasts ◽

Embryonic Fibroblasts ◽

Chronic Hcv Infection ◽

Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as determined by cell colony formation efficiency and the detection of HCV proteins and both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was found to replicate more efficiently in the PKR knockout (PKR−/−) MEF than in the wild-type (PKR+/+) MEF. The knockdown expression of PKR by specific small interfering RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by HCV RNA replication, indicating the activation of PKR-independent antiviral pathways. Furthermore, IFN-α/β inhibited HCV RNA replication in PKR−/− MEFs as efficiently as in PKR+/+ MEFs. These findings demonstrate that PKR-independent antiviral pathways play important roles in controlling HCV replication and mediating IFN-induced antiviral effect. Our findings also provide a foundation for the development of transgenic mouse models of HCV replication and set a stage to further define the roles of cellular genes in the establishment of chronic HCV infection and the mediation of intracellular innate antiviral response by using MEFs derived from diverse gene knockout animals.

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Chronic hepatitis C virus infection: Is there a correlation between HCV genotypes and the level of viremia?

Medicinski pregled ◽

10.2298/mpns0606230d ◽

2006 ◽

Vol 59 (5-6) ◽

pp. 230-234 ◽

Cited By ~ 2

Author(s):

Dragan Delic ◽

Zorica Nesic ◽

Jasmina Simonovic ◽

Neda Svirtlih ◽

Ljubisa Dokic ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Objective Assessment ◽

Hcv Infection ◽

Hcv Rna ◽

Genotype 4 ◽

Hcv Genotypes ◽

Genotype 2 ◽

Chronic Hcv Infection ◽

Chronic Hcv

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .

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Bezafibrate therapy reduces serum hepatitis C virus (HCV) RNA titre in patients with chronic HCV infection

Inpharma Weekly ◽

10.2165/00128413-200514690-00033 ◽

2005 ◽

Vol &NA; (1469) ◽

pp. 14

Author(s):

&NA;

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Serum Hepatitis ◽

Chronic Hcv Infection ◽

Chronic Hcv

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Hepatitis C virus infection among teenagers in an endemic township in Taiwan: epidemiological and clinical follow-up studies

Epidemiology and Infection ◽

10.1017/s0950268801006148 ◽

2001 ◽

Vol 127 (3) ◽

pp. 485-492 ◽

Cited By ~ 22

Author(s):

J. F. HUANG ◽

S. N. LU ◽

P. Y. CHUE ◽

C. M. LEE ◽

M. L. YU ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Follow Up Studies ◽

Screening Study ◽

Long Term Follow Up ◽

Chronic Hcv Infection ◽

Chronic Hcv

The aim of the study was to elucidate the epidemiological features of Hepatitis C virus (HCV) infection among teenagers in an endemic area by conducting a mass screening study. We also investigated the clinical outcome of the anti-HCV-positive subjects by conducting subsequent short-term and long-term follow-up studies. All 2837 students of two junior middle schools in Tzukuan, aged 13–16 years, were invited to be screened for anti-HCV, HBsAg, AST and ALT in October 1995. A total of 2726 (96%) students responded. Anti-HCV, HCV RNA and aminotransferase levels were evaluated among anti-HCV-positive students 1 month and 30 months later, respectively. A total of 38 (1·4%; M/F = 22/16) participants were anti-HCV-positive. The anti-HCV-positive students had higher rates of exposures to transfusion, anti-HCV-positive families and surgery. The prevalence (2·8%) of the 7 maritime villages was markedly higher than that (0·7%) of the other 8 villages (P < 0·001). Subsequent follow-up studies demonstrated that there might be 5 cases of acute or recent HCV infection, and 6 cases who had recovered from chronic HCV infection.

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Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity

Journal of Virology ◽

10.1128/jvi.75.15.7142-7148.2001 ◽

2001 ◽

Vol 75 (15) ◽

pp. 7142-7148 ◽

Cited By ~ 66

Author(s):

Amy J. Weiner ◽

Xavier Paliard ◽

Mark J. Selby ◽

Angelica Medina-Selby ◽

Doris Coit ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Protective Immunity ◽

Hcv Infection ◽

Hcv Rna ◽

Genetic Immunization ◽

Virus Rna ◽

Cast Doubt ◽

Chronic Hcv Infection ◽

Chronic Hcv

ABSTRACT Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual from subsequent infections and has cast doubt on the ability to develop effective vaccines. A series of intrahepatic genetic inoculations (IHGI) with type 1a HCV RNA were performed in a chimpanzee to determine whether a form of genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologous type 1a RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infectious doses of a heterologous type 1a (H77) and 1b (HC-J4) whole-virus inoculum. These results offer encouragement to pursue the development of HCV vaccines.

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