Special Issue “Chronic HCV Infection: Clinical Advances and Eradication Perspectives”

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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Lack of monomeric IgM anti-hepatitis C virus (HCV) core antibodies in patients with chronic HCV infection

Journal of Virological Methods ◽

10.1016/0166-0934(96)02058-7 ◽

1996 ◽

Vol 60 (2) ◽

pp. 179-182 ◽

Cited By ~ 6

Author(s):

Francesco Negro ◽

Hugo Troonen ◽

Gerd Michel ◽

Emiliano Giostra ◽

Monika Albrecht ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

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Acute hepatitis C virus infection

Eurosurveillance ◽

10.2807/ese.13.21.18879-en ◽

2008 ◽

Vol 13 (21) ◽

Cited By ~ 14

Author(s):

W L Irving ◽

D Salmon ◽

C Boucher ◽

I M Hoepelman

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Acute Hepatitis C ◽

Acute Hcv ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

The Individual ◽

Acute Hcv Infection ◽

Subsequent Risk

Around 25% of people infected with hepatitis C virus (HCV) are able to clear the infection spontaneously, while the majority become chronically infected, with a subsequent risk for the individual patient of progressive inflammatory liver disease, cirrhosis, hepatocellular carcinoma and liver-related death (Figure 1). Much is known about the epidemiology, pathogenesis, diagnosis and management of chronic HCV infection. In comparison, knowledge about acute HCV infection is patchy. In this article, we will highlight concerns relating to acute HCV infection and suggest that public health bodies responsible for managing the HCV epidemic should redirect at least some of their resources to dealing with these issues.

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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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Clinical, Biochemical and Virological Profile of Patients with Chronic Hepatitis C Virus Infection - A Study from University Hospital in Nepal

Journal of Nobel Medical College ◽

10.3126/jonmc.v4i1.13301 ◽

2015 ◽

Vol 4 (1) ◽

pp. 32-35

Author(s):

Dipesh Gurubacharya ◽

Mohan Khadka ◽

Khadga B Shreshta ◽

Prem Khadga ◽

Sashi Sharma

Keyword(s):

Hepatitis C Virus ◽

Viral Load ◽

Hepatitis C ◽

Drug Use ◽

Injection Drug Use ◽

Hcv Infection ◽

Genotype 3 ◽

Hcv Genotypes ◽

Chronic Hcv Infection ◽

Chronic Hcv

Introduction: Hepatitis C virus (HCV) infection is a major public health challenge. It is a major cause for cirrhosis and hepatocellular carcinoma worldwide. Both the genotype and viral load of HCV determine the choice of therapy as well as outcome of therapy. The aim of this study was to evaluate clinical, biochemical and virological profile and association of HCV genotypes with viral load and liver biochemical profile.Material and Methods: This was descriptive observational study of chronic HCV infected patients who attended at the outpatient clinic of Department of Gastroenterology of TUTH, IOM from April 2013 to November 2014. During this study period 38 patients with chronic HCV infection were analyzed. Clinical profile, possible risk factors for transmission of HCV infection and liver biochemical profile were recorded. Virological profile included HCV viral load and HCV genotypes.Results: Out of 38 patients 34(89.5%) were male and 4(10.5%) were female. Injection drug use (IDU) was the most common mode for acquisition of HCV infection (55.3%). Genotype 3 was found in 21(55.26%) patients and genotype 1 was found in 17(44.74%) patients. There was no significant association between HCV genotypes and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. And also there was no significant association between HCV viral load and different HCV genotypes.Conclusions: In our study HCV genotype 3 was the most prevalent genotype in patients with chronic HCV infection. Injection drug use was identified as most common identifiable risk factor for transmission of HCV infection. There was no significant association between different HCV genotypes and serum ALT, AST level and HCV viral load. Journal of Nobel College of Medicine Vol.4(1) 2015: 32-35

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