scholarly journals Natural Cytotoxicity Receptor–Dependent Natural Killer Cytolytic activity Directed at Hepatitis C Virus (HCV) Is Associated With Liver Inflammation, African American Race, IL28B Genotype, and Response to Pegylated Interferon/Ribavirin Therapy in Chronic HCV Infection

2013 ◽  
Vol 209 (10) ◽  
pp. 1591-1601 ◽  
Author(s):  
Qinglai Meng ◽  
M. R. Sandhya Rani ◽  
Julia M. Sugalski ◽  
Chelsey J. Judge ◽  
Sarah Phat ◽  
...  
2019 ◽  
Vol 6 (2) ◽  
pp. 3016-3026 ◽  
Author(s):  
Marjan Mokhtare ◽  
Ahmad Darvishi Zeidabadi ◽  
Mansour Bahardoust ◽  
Saeid Safari ◽  
Mitra Barati ◽  
...  

Introduction: Hepatitis C virus (HCV) infection affects almost 180 million people around the world. Even though the development of direct acting antivirals (DAAs) has significantly improved the treatment responses to HCV infection, treatment with pegylated interferon (PegIFN) in combination with ribavirin is considered the standard of care (SOC) for chronic HCV infection treatment in countries with limited medical resources. Considering the inhibitory effect of vitamin B12 on HCV replication, we have evaluated the effect of vitamin B12 supplementation along with SOC on treatment outcomes in patients with chronic HCV infection, who were antiviral treatment-naive. Methods: In this regard, seventy-four HCV-infected patients, naïve to antiviral therapy, were randomly assigned to receive SOC or SOC in addition to vitamin B12 (SOC + B12). Viral response was evaluated at 4, 12, 24 and 48 weeks following the initiation of viral treatment and at 24 weeks after completing the treatment. Genotyping of the interleukin 28B (IL28B) polymorphisms was also performed. Demographic characteristics, clinical findings, fibroscan results and drug adverse effects were recorded. Results: Our findings showed that rapid viral response was not significantly different between the two groups; however, the rates of complete early viral response (cEVR) (p=0.033), end-of-treatment viral response (ETVR) (p=0.001) and sustained virologic response (SVR) (p=0.0001) were significantly higher in SOC + B12 patients compared to SOC patients. Besides, in SOC + B12 patients, those with a higher baseline viral load and carriers of IL28B CC genotype showed significantly higher rate of SVR. Conclusion: In conclusion, the addition of vitamin B12 significantly improved the rate of SVR in HCV-infected patients, who were naïve to antiviral therapy. As this treatment regimen is safe and inexpensive, it proposes an option for improving the effectiveness of the HCV treatment with SOC, particularly in resource-limited settings.  


2006 ◽  
Vol 80 (18) ◽  
pp. 9144-9150 ◽  
Author(s):  
Natalia Paladino ◽  
Hugo Fainboim ◽  
Graciela Theiler ◽  
Teresa Schroder ◽  
Alberto Eduardo Muñoz ◽  
...  

ABSTRACT Elevated levels of interleukin 10 (IL-10) were previously described for chronically hepatitis C virus (HCV)-infected patients. We determined by a sequence-specific oligonucleotide probing technique the IL-10 promoter genotypes in 286 Argentinean HCV patients grouped according to disease outcome. The GG genotype (position −1082) is known to be associated with high IL-10 production, GA is considered an intermediate producer, and AA is associated with low IL-10 production. We found an increase in frequency of the GG genotype in female patients who do not eliminate the virus (RNA+). In these patients, the GG frequency was 0.19, versus 0.10 in controls (P = 0.03). This association became more significant in those RNA+ female patients with elevated hepatic transaminases (GG frequency of 0.25; P = 0.0013). Additionally, this genotype frequency was higher in noncirrhotic female patients than in controls (GG frequency for noncirrhotic female patients was 0.31; P = 0.009). In RNA− patients, the GA frequency was elevated compared with that in controls (GA frequency of 0.76 in RNA− patients versus 0.48 in controls; P = 0.01), that in all HCV patients (GA frequency of 0.43; P = 0.001), and that in RNA+ patients (GA frequency of 0.40; P = 0.0005). We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype. The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of the HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients.


1994 ◽  
Vol 39 (9) ◽  
pp. 2022-2031 ◽  
Author(s):  
Shinjiro Sato ◽  
Shigetoshi Fujiyama ◽  
Motohiko Tanaka ◽  
Masafumi Goto ◽  
Yuko Taura ◽  
...  

2001 ◽  
Vol 45 (2) ◽  
pp. 517-524 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Lawrence Feinman ◽  
Leonard Liebes ◽  
Nancy Ostrow ◽  
Victoria Koslowski ◽  
...  

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.


2006 ◽  
Vol 80 (15) ◽  
pp. 7364-7374 ◽  
Author(s):  
Kyung-Soo Chang ◽  
Zhaohui Cai ◽  
Chen Zhang ◽  
Ganes C. Sen ◽  
Bryan R. G. Williams ◽  
...  

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.


1996 ◽  
Vol 60 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Francesco Negro ◽  
Hugo Troonen ◽  
Gerd Michel ◽  
Emiliano Giostra ◽  
Monika Albrecht ◽  
...  

2016 ◽  
Vol 63 (2) ◽  
pp. 123-127

Hepatitis C virus (HCV) is a virus known to infect the liver. In last years, accumulated evidences has demonstrate the presence and active HCV replication in extrahepatic tissues. There are currently epidemiological, clinical, immunohistochemical and imaging data suggesting involvement of HCV in myocardial disease. The recognition of myocardial dysfunction as extrahepatic manifestations of chronic HCV infection is of special importance with significant clinical and therapeutical impact.


2008 ◽  
Vol 13 (21) ◽  
Author(s):  
W L Irving ◽  
D Salmon ◽  
C Boucher ◽  
I M Hoepelman

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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