scholarly journals Hepatitis C Virus RNA Is Commonly Detectable in Rectal and Nasal Fluids of Patients With High Viremia

2019 ◽  
Vol 71 (5) ◽  
pp. 1292-1299
Author(s):  
David Chromy ◽  
Ralf Schmidt ◽  
Mattias Mandorfer ◽  
Gerold Felician Lang ◽  
David Bauer ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Risk ◽  
Transmitted Disease ◽  
High Serum ◽  
Western World ◽  
Hcv Rna ◽  
Hcv Transmission ◽  
Sex Practices ◽  
Rna Levels

Abstract Background Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood. Methods Forty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires. Results Median age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P < .001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively. Conclusions HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing “tools” might be important HCV transmission routes, especially in patients with high serum HCV-RNA.

Serum Hepatitis C Virus RNA Levels and Histologic Findings in Liver Allografts With Early Recurrent Hepatitis C

2000 ◽  
Vol 124 (11) ◽  
pp. 1623-1627 ◽  
Author(s):  
Young Nyun Park ◽  
Peter Boros ◽  
David Y. Zhang ◽  
Patricia Sheiner ◽  
Leona Kim-Schluger ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Biopsy ◽  
Activity Index ◽  
Hcv Rna ◽  
Recurrent Hepatitis ◽  
Biopsy Specimens ◽  
Histologic Activity Index ◽  
Recurrent Hepatitis C ◽  
Rna Levels

Abstract Background.—Histopathologic features of early recurrent hepatitis C after orthotopic liver transplantation (OLTx) may be modified by immunosuppressive therapy or complicated by other conditions. Hepatitis C virus (HCV) RNA level usually increases after OLTx, but its correlation to histologic findings is not clear. Objective.—To evaluate the histologic findings of early recurrent hepatitis C in liver allografts and its correlation to serum HCV RNA level. Methods.—We studied 14 patients who underwent OLTx for chronic HCV infection. Thirty liver biopsy specimens and HCV RNA levels of 22 corresponding plasma samples obtained during the first 6 months following OLTx were analyzed. The control group (9 patients, 25 biopsy specimens) was chosen at random from patients with chronic liver disease other than HCV who were undergoing OLTx, and all tested negative for HCV RNA by polymerase chain reaction after OLTx. Results.—Statistically significant pathological features of early recurrent HCV infection were the number of acidophilic bodies, piecemeal necrosis, lymphocyte predominance in the portal tracts, and fibrous septum. These findings and histologic activity index scores increased with time after OLTx. The HCV RNA levels determined by branched DNA assay showed no significant correlation with histologic features. However, patients with higher histologic activity index scores tended to have higher RNA levels. Conclusions.—Liver biopsy specimens are helpful for the diagnosis or confirmation of early recurrent hepatitis C in liver allografts, but serial biopsy specimens are sometimes required for definite diagnosis. The HCV RNA levels are usually higher in patients who display signs of more severe liver damage.

scholarly journals mTORC1 Restricts Hepatitis C Virus Replication Through ULK1-mediated Suppression of miR-122 and Facilitates Post-replication Events

2018 ◽  
Author(s):  
Manish Kumar Johri ◽  
Hiren Vasantrai Lashkari ◽  
Dhiviya Vedagiri ◽  
Divya Gupta ◽  
Krishnan Harinivas Harshan
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Infection ◽  
Virus Replication ◽  
Viral Rna ◽  
Hcv Rna ◽  
Significant Drop ◽  
Mechanistic Target Of Rapamycin ◽  
Mtorc1 Activation ◽  
Rna Levels

ABSTRACTMechanistic target of rapamycin (mTOR) is an important kinase that assimilates several upstream signals including viral infection and facilitates appropriate response by the cell through two unique complexes mTORC1 and mTORC2. Here, we demonstrate that mTORC1 is activated early during HCV infection as antiviral response. Pharmacological inhibition of mTORC1 promoted HCV replication as suggested by elevated levels of HCV (+) and (-) RNA strands. This was accompanied by significant drop in extracellular HCV RNA levels indicating defective post-replication stages. The increase in viral RNA levels failed to augment intracellular infectious virion levels, suggesting that mTORC1 inhibition is detrimental to post-replication steps. Lower infectivity of the supernatant confirmed this observation. Depletion of Raptor and ULK1 accurately reproduced these results suggesting that mTORC1 imparted these effects on HCV through mTORC1-ULK1 arm. Interestingly, ULK1 depletion resulted in increased levels of miR-122, a critical host factor for HCV replication, thus revealing a new mechanism of regulation by ULK1. The binary effect of mTORC1 on HCV replication and egress suggests that mTORC1-ULK1 could be critical in replication: egress balance. Interestingly we discover that ULK1 depletion did not interfere with autophagy in Huh7.5 cells and hence the effects on HCV replication and post-replication events are not resultant of involvement of autophagy. Our studies demonstrate an overall ULK1 mediated anti-HCV function of mTORC1 and identifies an ULK1-independent autophagy that allows HCV replication in spite of mTORC1 activation.

scholarly journals Poly(I:C) and Lipopolysaccharide Innate Sensing Functions of Circulating Human Myeloid Dendritic Cells Are Affected In Vivo in Hepatitis C Virus-Infected Patients

2007 ◽  
Vol 81 (11) ◽  
pp. 5537-5546 ◽  
Author(s):  
Ian Gaël Rodrigue-Gervais ◽  
Loubna Jouan ◽  
Geneviève Beaulé ◽  
Dominike Sauvé ◽  
Julie Bruneau ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Poly I:C ◽  
Hcv Rna ◽  
Genomic Rna ◽  
Tnf Α ◽  
Wide Range ◽  
Rna Levels

ABSTRACT The role of peripheral dendritic cells (DCs) in hepatitis C virus (HCV) infection is unclear. To determine if persistent infection exerts an inhibitory pressure on HCV-specific innate responses, we analyzed DC function in blood through quantification of cell-associated HCV RNA levels in conjunction with multiparametric flow cytometry analysis of pathogen recognition receptor-induced cytokine expression. Independently of the serum viral load, fluorescence-activated cell sorter-purified total DCs had a wide range of cell-associated HCV genomic RNA copy numbers (mean log10, 5.0 per 106 cells; range, 4.3 to 5.8). Here we report that for viremic patients with high viral loads in their total DCs, the myeloid DC (MDC) subset displayed impaired expression of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) but normal IL-6 or chemokine CCL3 expression in response to poly(I:C) and lipopolysaccharide (LPS). IL-6-expressing cells from this subgroup of viremic patients demonstrated a significant increase (sixfold more) in TNF-α− IL-12− cell frequency compared to healthy donors (mean, 38.8% versus 6.5%; P < 0.0001), indicating a functional defect in a subpopulation of cytokine-producing MDCs (∼6% of MDCs). Attenuation of poly(I:C) and LPS innate sensing was HCV RNA density dependent and did not correlate with viremia or deficits in circulating MDC frequencies in HCV-infected patients. Monocytes from these patients were functionally intact, responding normally on a per-cell basis following stimulation, independent of cell-associated HCV RNA levels. Taken together, these data indicate that detection of HCV genomic RNA in DCs and loss of function in the danger signal responsiveness of a small proportion of DCs in vivo are interrelated rather than independent phenomena.

scholarly journals MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Isaac Ruiz ◽  
Quentin Nevers ◽  
Eva Hernández ◽  
Nazim Ahnou ◽  
Rozenn Brillet ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatoma Cell ◽  
Hcv Rna ◽  
Dependent Manner ◽  
Cysteinyl Leukotriene ◽  
Leukotriene Receptor ◽  
Cysteinyl Leukotriene Receptor ◽  
Dose Dependent ◽  
Rna Levels

ABSTRACT The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct-acting antiviral (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with a 50% effective concentration (EC50 ± standard deviation) of 9 ± 0.3 μM and a maximum HCV RNA level reduction of approximatively 1 log10. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonist SR2640 increased HCV-subgenomic replicon (SGR) RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

scholarly journals Hepatitis C Virus Screening of High-Risk Patients in a Canadian Emergency Department

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kelsey Ragan ◽  
Anjali Pandya ◽  
Tristan Holotnak ◽  
Katrina Koger ◽  
Neil Collins ◽  
...  
Keyword(s):  
Emergency Department ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Risk ◽  
Drug Use ◽  
Hcv Rna ◽  
High Risk Patients ◽  
Risk Patients ◽  
History Of ◽  
Hcv Screening

Background. Approximately 0.7% of the Canadian population is infected with hepatitis C virus (HCV), and many individuals are unaware of their infection. Our objectives were to utilize an emergency department (ED) based point-of-care (POC) HCV screening test to describe our local population and estimate the proportion of high-risk patients in our population with undiagnosed HCV. Methods. A convenience sample of medically stable patients (≥18 years) presenting to a community ED in Calgary, AB, between April and July 2018 underwent rapid clinical screening for HCV risk factors, including history of injection drug use, healthcare in endemic countries, and other recognized criteria. High-risk patients were offered POC HCV testing. Antibody-positive patients underwent HCV-RNA testing and were linked to hepatology care. The primary outcome was the proportion of new HCV diagnoses in the high-risk population. Results. Of the 999 patients screened by survey, 247 patients (24.7%) were high-risk and eligible for testing. Of these, 123 (49.8%) were from HCV-endemic countries, while 63 (25.5%) and 31 (12.6%) patients endorsed a history of incarceration and intravenous drug use (IVDU), respectively. A total of 144 (58.3%) eligible patients agreed to testing. Of these, 6 patients were POC-positive (4.2%, CI 0.9–7.4%); all 6 had antibodies detected on confirmatory lab testing and 4 had detectable HCV-RNA viral loads in follow-up. Notably, 103 (41.7%) patients declined POC testing. Interpretation. Among 144 high-risk patients who agreed to testing, the rate of undiagnosed HCV infection was 4.2%, and the rate of undiagnosed HCV infection with detectable viral load was 2.8%. Many patients with high-risk clinical criteria refused POC testing. It is unknown if tested and untested groups have the same disease prevalence. This study shows that ED HCV screening is feasible and that a small number of previously undiagnosed patients can be identified and linked to potentially life-changing care.

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