Ultracentrifugation and concentration of a large volume of serum for HCV RNA during treatment may predict sustained and relapse response in chronic HCV infection

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

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Demonstration and Distribution of HCV RNA Sequences by in situ Hybridization and HCV-Related Proteins by Immunohistochemistry in the Liver Tissue of Patients with Chronic HCV Infection

Pathobiology ◽

10.1159/000163956 ◽

1995 ◽

Vol 63 (5) ◽

pp. 239-248 ◽

Cited By ~ 10

Author(s):

Domenico Sansonno ◽

Vito Cornacchiulo ◽

Anna Rina Iacobelli ◽

Pietro Gatti ◽

Maria Di Stasi ◽

...

Keyword(s):

In Situ Hybridization ◽

Liver Tissue ◽

Hcv Infection ◽

Hcv Rna ◽

Rna Sequences ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Related Proteins

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Efficacy of Weeks 4 and 12 Post-therapy HCV RNA Levels in Determining Sustained Virological Response [SVR] after Completing 24 or 48 Weeks of Telaprevir-based Triple Therapy for Chronic HCV Infection

The American Journal of Gastroenterology ◽

10.14309/00000434-201310001-00400 ◽

2013 ◽

Vol 108 ◽

pp. S119

Author(s):

Irfan Alam ◽

Shadi Giani ◽

Ammar Hassan

Keyword(s):

Triple Therapy ◽

Sustained Virological Response ◽

Virological Response ◽

Hcv Infection ◽

Hcv Rna ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Post Therapy ◽

Rna Levels

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Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.517-524.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 517-524 ◽

Cited By ~ 84

Author(s):

Jeffrey M. Jacobson ◽

Lawrence Feinman ◽

Leonard Liebes ◽

Nancy Ostrow ◽

Victoria Koslowski ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Pharmacokinetic Data ◽

Serious Adverse Events ◽

Dosing Schedule ◽

Diarrhea Virus ◽

Chronic Hcv Infection ◽

Chronic Hcv

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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