RESUMO
Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.
Assuntos
Hepatite C , Ácidos Nucleicos , Transplante de Órgãos , Humanos , Hepacivirus/genética , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológicoRESUMO
Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.
Assuntos
Colestase , Crioglobulinemia , Hepatite C Crônica , Hepatite C , Masculino , Humanos , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Estudos de Casos e Controles , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/etiologia , Estudos Retrospectivos , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Colestase/complicações , Colestase/tratamento farmacológico , Biomarcadores , RNARESUMO
The complexity of the hepatitis C virus (HCV) diagnostic workflow and stringent criteria for universal health coverage are significant barriers to achieving HCV elimination in Thailand. A test-to-treat strategy using a rapid diagnostic test (RDT) for screening at point of care, followed by a qualitative nucleic acid testing, is a promising strategy to facilitate population-wide screening for HCV infection and expedite time to treatment. This strategy was evaluated in Phetchabun province, Thailand, where the HCV burden is relatively high. This simplified HCV test-to-treat strategy showed strong potential to be implemented at a national level. Several obstacles to implementation included the stringent criteria for universal health coverage, which prioritizes patients with advanced disease, the continuous policy revision for HCV treatment and care, the relatively low public awareness of HCV infection, and the lagging of government policy prioritization. All of these contribute to the delayed progress in hepatitis elimination.
Assuntos
Hepatite A , Hepatite C , Humanos , Hepacivirus/genética , Tailândia/epidemiologia , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , GovernoRESUMO
According to the French recommendations, the elimination of the hepatitis C virus by 2025 could be a realistic public health goal. Screening policies are being intensified, and access to treatment is promoted for patients who escape the usual care pathway. The 'Scanvir' program is an original strategy based on dedicated screening days, as part of the 'test, treat and cure HCV' event in addiction care centers in a French region, during which innovative screening technologies (RDTs, FibroScan® and point-of-care HCV RNA testing) are brought on site and access to a multidisciplinary team is offered. A total of 392 patients attended the 67 regional Scanvir sessions: 31.6% were HCV Ab-positive and 66% of them were HCV RNA-positive. Treatment was initiated in 79.3% of the patients. RDTs were accepted by 62% of the PWIDs (including those who already knew their status) and FibroScan® by 99.5% of the patients. 80% of the viremic patients started their treatment on site and are now cured or still under treatment. Advanced fibrosis evaluated by FibroScan® (LSM > 8 KPa) was suspected in 13.4% and 14.1% of the global and the HCV population, respectively. Scanvir is an efficient strategy for HCV elimination based on dedicated days aimed at increasing cost-effectiveness and offering a multidisciplinary service while saving human care resources. It is an exportable strategy that also offers comprehensive screening of associated chronic liver diseases via the elastometry device and interviews.
Assuntos
Usuários de Drogas , Hepatite C , Humanos , Hepacivirus/genética , Hepatite C/epidemiologia , França , RNA , Antivirais/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Screening strategies for undiagnosed infections are fundamental for hepatitis C virus (HCV) elimination. We previously investigated HCV prevalence and screening strategies in an urban primary care setting. IV drug abuse, blood transfusion before 1992, immigration, or elevated ALT were identified as risk factors in a post hoc analysis and diagnosed 83% of unknown HCV-RNA-positive cases by screening only 26% of the population. We aimed to validate prospectively the proposed screening algorithm in two independent urban and rural cohorts and to analyse for potential differences. METHODS: Anti-HCV and ALT were included in a routine check-up together with a questionnaire covering risk factors. HCV-RNA was analysed in anti-HCV-positive individuals. RESULTS: In urban and rural areas, 4323 and 9321 individuals were recruited. The anti-HCV prevalence was 0.56% and 0.49%, and 0.1% of patients were HCV-RNA-positive in both regions. Fifty-two anti-HCV positive patients including eight HCV-RNA-positive cases were unaware of the infection (number needed to screen to detect one unknown anti-HCV-positive individual: 262). At least one of the three aforementioned risk factors or elevated serum ALT was present in 3000 patients (22%). Restricting HCV screening to only those with risk factors, 52% and 75% of all anti-HCV and HCV-RNA-positive undiagnosed patients were identified (number needed to screen: 111). CONCLUSIONS: We confirm prospectively the efficiency of a risk-based HCV screening. The risk-based algorithm should be evaluated in other countries with similarly low HCV prevalence as in Germany to achieve WHO HCV elimination goals.
Assuntos
Anticorpos Anti-Hepatite C , Hepatite C , Humanos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepacivirus/genética , Programas de Rastreamento , RNA Viral , Prevalência , Atenção Primária à SaúdeRESUMO
BACKGROUND: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA. METHODS: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates. RESULTS: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%). CONCLUSIONS: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.
Assuntos
Hepacivirus , Hepatite C , Teste em Amostras de Sangue Seco/métodos , Hepacivirus/genética , Humanos , Testes Imediatos , RNA Viral/genética , Sensibilidade e Especificidade , Carga Viral/métodosRESUMO
Universal hepatitis C screening in pregnancy is not recommended by NICE due to a lack of effective interventions to prevent mother to child transmission (MTCT) and is only offered to pregnant women at increased risk of infection (intra-venous drug use [IVDU] or with a HCV positive family member). No testing is offered to patients from high endemic areas. However, data regarding true seroprevalence in multi-ethnic inner-city populations in the UK are required. This study aimed to determine test positivity rates of HCV infection in an unselected South East London ethnically diverse population of pregnant women by universal screening during routine antenatal care compared with a "targeted" screening approach. "Targeted" risk-based screening was performed in two eras (2016, n = 1002) and subsequently in 2018, after modifying the HCV risk questionnaire (n = 1122). Universal opt out screening was similarly performed in two eras in 2017 (n = 1012) and again in 2019 (n = 1057). During screening for HBV, HIV and syphilis, anti-HCV was tested, followed by an iterative HCV RNA test in those positive for anti-HCV. All anti-HCV-positive women were referred to the specialist hepatology service, and testing was offered to all family members. All HCV RNA-positive patients were followed during pregnancy and post-delivery period and were offered treatment. All infants of HCV RNA-positive mothers were linked to care with paediatric team. In the 2016 "targeted" screening cohort 212/1002 had a risk of BBV (blood borne viral) infection and (0.6%) were anti-HCV positive and HCV RNA positive. 0.3% patients were newly diagnosed. In the 2017 universal screening cohort, 1012/1038 pregnant women consented to testing. 0.96% were anti-HCV positive and 0.86% women were HCV RNA positive with 0.67% newly diagnosed. After modification of the risk-based questionnaire, a second risk-based targeted cohort were tested in 2018: 342/1122 (31%) were assessed as at risk and were offered an anti-HCV test. 0.71% were anti-HCV positive and 0.27% were HCV RNA positive. In the 2019 cohort tested by universal screening, 1049/1057 women were tested and 0.85% tested positive for anti-HCV, 0.28% women were HCV RNA positive. All newly diagnosed patients were born abroad. All patients had mild liver disease and had normal pregnancies. All patients were treated post-delivery and achieved SVR. All patients were negative for other BBV infections. In conclusion, the anti-HCV test positive rate in this ethnically diverse pregnant cohort ranged between 0.96% and 0.6% (whole cohort) but the rate depended upon the era and screening methodology used. Universal screening detected a higher numbers of anti-HCV positive women during pregnancy, including those not previously aware of their hepatitis C. While there was not significant drop in seroprevalence in pregnant women between 2016 and 2019, we observed that the ratio of HCV RNA positive to anti-HCV positive women has declined over time, from 0.86% in 2016 (100% HCV RNA+) to 0.28% in 2019 (33% HCV RNA+) for whole cohort probably due to increased HCV treatment rates from 2016. These data have important implications for hepatitis C testing in pregnancy and the appropriate methodology to use for maximal accuracy.
Assuntos
Hepatite C , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , Criança , Masculino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Estudos Soroepidemiológicos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Programas de Rastreamento/métodos , Hepacivirus/genética , Anticorpos Anti-Hepatite C , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , RNA , Fatores de RiscoRESUMO
People living with HIV (PLHIV) are a priority population to receive hepatitis C virus (HCV) screening and treatment. We aimed to characterize the HCV care cascade among PLHIV between 2010 and 2018 and to compare HCV testing and treatment uptake pre- and post-availability of direct-acting antivirals (DAAs) in New South Wales (NSW), Australia. Records of all HCV notifications (1993-2017) were linked to HIV notifications, deaths, hospitalizations, incarcerations, opioid agonist therapy, HCV RNA testing and treatment databases. Numbers and proportions were calculated for all stages of the care cascade and factors associated with HCV testing, and DAA treatment uptake were evaluated using logistic regression. From 383 individuals with HCV notification (2009-2017), 349 (91%) were ever HCV RNA tested, 285 (74%) had an indicator of chronic HCV infection, and from those eligible for treatment, 210 (74%) received HCV treatment. HCV testing was recorded for 85% pre-DAA era and reached a cumulative proportion of 90% post-DAA while treatment uptake had a 10-fold increase from 7% pre- to 73% post-DAA era. Younger age (adjusted odds ratio [aOR] 0.98; 95% CI 0.96-0.99), female gender (aOR 1.87; 95% CI 1.10-3.19), and rural region residence at notification (aOR 1.56; 95% CI 1.03-2.36) were associated with not receiving HCV testing. No identified factor was associated with not receiving treatment post-DAA era. Removing barriers to HCV testing, expanding treatment to a variety of settings and continuous education and harm reduction are essential to achieve HCV elimination among PLHIV in Australia.
Assuntos
Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Austrália/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Armazenamento e Recuperação da Informação , New South Wales/epidemiologia , RNARESUMO
BACKGROUND: Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations. METHODS: We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard). RESULTS: One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%-35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2â =â 0.96). CONCLUSIONS: The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility.
Assuntos
Hepacivirus , Hepatite C , Austrália , Teste em Amostras de Sangue Seco , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Humanos , Flebotomia , RNA Viral/isolamento & purificação , Sensibilidade e Especificidade , Carga ViralRESUMO
BACKGROUND & AIMS: Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment. METHODS: We performed a case-control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay. RESULTS: Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (<4 log IU/mL in 11 of 12) and normal levels of alanine aminotransferase at the time of relapse, much like patients with an SVR12. There was no significant difference between the spontaneous clearance group and the SVR12 group in magnitude and breadth of HCV-specific T cell responses. CONCLUSIONS: In a case-control study of patients who spontaneously cleared chronic HCV infection following a relapse after DAA therapy, we found that it is important to confirm viremia prior to retreatment after the relapse-particularly for individuals with low levels of HCV RNA and normal or near-normal levels of alanine aminotransferase after treatment.
Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Estudos de Casos e Controles , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Recidiva , Resposta Viral SustentadaRESUMO
OBJECTIVES: Despite recombinant interferon-λ 4 (IFN-λ4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that IFN-λ4 may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV). MATERIALS AND METHODS: Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay. RESULTS: Patients producing IFN-λ4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-λ4 (IFNL4rs12979860 CT/TT versus CC, p<.0001, Mann-Whitney U-test). Additionally, in univariate analyses S/CO was significantly higher in men than women (p<.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0-2 versus 3-4, p = .009), and absent/mild steatosis (grade 0-1 versus 2-3, p = .0005). Also, an inverse correlation with HCV RNA level (rs= -0.14, p = .02) was noted. In multivariate analysis IFN-λ4, gender, steatosis and viral load remained independently associated. CONCLUSIONS: To our knowledge, this is the first report that demonstrates that the ability to produce IFN-λ4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-λ4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection. ClinicalTrials.gov Identifier: NCT00143000.
Assuntos
Hepatite C Crônica , Hepatite C , Animais , Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Interleucinas/genética , Masculino , Polimorfismo de Nucleotídeo Único , Carga ViralRESUMO
BACKGROUND: As a blood-borne pathogen, hepatitis C virus (HCV) has long been a major threat associated with needle-stick injuries (NSIs) mainly because no vaccine is available for HCV. Following an NSI, we usually test the source patient for HCV antibody (HCV-Ab). Since HCV-Ab positivity does not necessarily indicate current infection, HCV RNA is further examined in patients positive for HCV-Ab. Direct-acting antivirals (DAAs) have enabled us to treat most HCV-infected patients; therefore, we speculate that the rate of HCV RNA positivity among HCV-Ab-positive patients decreased after the emergence of DAAs. This cross-sectional study was performed to investigate the change in the actual HCV RNA positivity rate in source patients before and after the interferon (IFN)-free DAA era. METHODS: This was a cross-sectional study of NSI source patients at a tertiary academic hospital in Japan from 2009 to 2019. IFN-free DAA regimens were first introduced in Japan in 2014. Accordingly, we compared HCV status of NSI source patients that occurred between 2009 and 2014 (the era before IFN-free DAAs) with those that occurred between 2015 and 2019 (the era of IFN-free DAAs) in a tertiary care hospital in Japan. RESULTS: In total, 1435 NSIs occurred, and 150 HCV-Ab-positive patients were analyzed. The proportion of HCV RNA-positive patients significantly changed from 2009 through 2019 (p = 0.005, Cochran-Armitage test). Between 2009 and 2014, 102 source patients were HCV-Ab-positive, 78 of whom were also positive for HCV RNA (76.5%; 95%CI, 67.4-83.6%). Between 2015 and 2019, 48 patients were HCV-Ab-positive, 23 of whom were also positive for HCV RNA (47.9%; 95%CI, 34.5-61.7%; p = 0.0007 compared with 2009-2014). In the era of IFN-free DAAs, 9 of 23 HCV RNA-negative patients (39.1%) and 2 of 22 HCV RNA-positive patients (9.1%) were treated with an IFN-free combination of DAAs (p = 0.0351). Regarding the departments where NSIs occurred, HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs (p = 0.0078, compared with 2009-2014). CONCLUSIONS: Actual HCV RNA positivity in source patients of NSIs decreased after the emergence of IFN-free DAAs. IFN-free DAAs might have contributed to this reduction, and HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/etiologia , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Idoso , Estudos Transversais , Feminino , Pessoal de Saúde/estatística & dados numéricos , Hepatite C/tratamento farmacológico , Anticorpos Anti-Hepatite C/sangue , Humanos , Incidência , Interferons/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Ferimentos Penetrantes Produzidos por Agulha/tratamento farmacológico , Traumatismos Ocupacionais/epidemiologia , Traumatismos Ocupacionais/etiologia , RNA Viral/sangue , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: To explore associations between PON1 rs854560, rs662, 705,379, HCV clearance, and interactions between tested PON1 single nucleotide variants (SNVs) and interferon-λ4 gene (IFNL4) rs368234815 variant in hemodialyzed individuals. METHODS: The study included 83 HD individuals who spontaneously resolved HCV infection (all had known IFNL4 rs368234815 variant) and 104 individuals with persistently positive blood tests for HCV RNA (102 were IFNL4 rs368234815 variant successfully genotyped). We genotyped PON1 by high-resolution melt analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). We used a logistic regression model to assess the association between genetic data and HCV outcome while adjusting for clinical confounding variables. Epistatic interactions between tested PON1 SNVs and IFNL4 rs368234815 were analyzed by the multifactor dimensionality reduction method. RESULTS: In the recessive inheritance model, PON1 rs662 GG (OR 9.94, 95% CI 1.20-82.7, P = 0.022) and rs854560 TT (OR 4.31, 95% CI 1.62-11.5, P = 0.003) genotypes were associated with a higher probability for HCV clearance. The haplotype composed of rs662A_rs854560A_rs705379 was not associated with spontaneous HCV clearance. The IFNL4 rs368234815 TT/TT variant was equally distributed among individuals bearing different PON1 SNVs. The epistatic gene-gene analysis did not reveal the interaction between tested PON1 SNVs and IFNL4 rs368234815 (P = 0.094). Regression model, including the PON1 rs662 GG genotype, the PON1 rs854560 genotype, the IFNL4 rs368234815 TT/TT genotype, age at RRT onset, RRT duration, and chronic glomerulonephritis as possible explanatory variables for spontaneous HCV clearance, showed that significant predictors of spontaneous HCV clearance were the IFNL4 rs368234815 TT/TT genotype (OR 2.607, 95% CI 1.298-5.235, P = 0.007), PON1 rs854560 TT (OR 6.208, 1.962-19.644, P = 0.002), PON1 rs662 GG (OR 10.762, 1.222-94.796, P = 0.032), and RRT duration (OR 0.930, 95% CI 0.879-0.984, P = 0.011). CONCLUSION: In HD individuals, PON1 rs662 GG and rs854560 TT are associated with a higher frequency of spontaneous HCV clearance.
Assuntos
Hepatite C Crônica , Hepatite C , Arildialquilfosfatase/genética , Estudos de Casos e Controles , Genótipo , Hepacivirus/genética , Hepatite C Crônica/genética , Humanos , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Diálise RenalRESUMO
OBJECTIVE: To discuss the clinical significance of HCV-cAg testing in the diagnosis, activity determination, and monitoring of therapeutic effectiveness of HCV infection and its advantages compared with HCV-RNA and anti-HCV antibodies detection. METHODS: By summarizing the published literature, the advantages and significance of HCV core antigen detection were sought. RESULTS: The expression of HCV-cAg is highly consistent with that of HCV-RNA, but compared with HCV-RNA, detection of HCV-cAg is easy to operate, time saving, and low cost. HCV-cAg can be detected within 12~15 days after infection, and the window period can be shortened by5~7 weeks. HCV-cAg is a serological indicator of virus replication, which can distinguish previous infection of HCV or current infection. HCV-cAg detection is more suitable for immunocompromised, hemodialysis, organ transplant patients. HCV-cAg also can be used to monitor antiviral efficacy and predict sustained virological response (SVR). CONCLUSION: HCV core antigen has similar clinical sensitivity to NAT and can be used as a substitute for HCV-RNA in the diagnosis of virus infection. Combined detection of HCV-cAg and antibody serology can help doctors detect HCV infection earlier, accurately diagnose different stages of HCV infection, and evaluate the therapeutic effect of antiviral drugs, which are beneficial in the prevention and treatment of hepatitis C.
Assuntos
Antígenos da Hepatite C/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C/diagnóstico , Proteínas do Core Viral/sangue , Análise Custo-Benefício , Testes Hematológicos/economia , Testes Hematológicos/métodos , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/sangue , Humanos , RNA Viral/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Between December 2018 and January of 2019, we evaluated the accuracy of the point-of-care Hepatitis C (HCV) antibody test (POC; OraQuick HCV) used at a community-based needle and syringe exchange program serving persons who inject drugs in Tallinn, Estonia. METHODS: We compared the results of screening for HCV antibodies by OraQuick (oral swab) and enzyme immunoassay (EIA; blood draw) and assessed test results implications in a high prevalence setting. Findings Of the 100 participants, 88 (88%) had reactive POC test results, and 93 were HCV antibody positive on EIA testing. Sensitivity, specificity and negative predictive value (NPV) for the POC assay with EIA as the relevant reference test were as follows: 94.6% (95% CI 90.0-99.2%), 100% and 58.3% (95% CI 30.4-86.2%). Of the 12 testing, HCV-negative with the POC only 7 (58.3%) were true negatives. CONCLUSIONS: Oral swab rapid testing HCV screening in this nonclinical setting was sensitive and specific but had unacceptably low NPV. In high prevalence settings, POC tests with high sensitivity and that directly measure HCV RNA may be warranted.
Assuntos
Usuários de Drogas , Hepatite C , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Estônia/epidemiologia , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Prevalência , Abuso de Substâncias por Via Intravenosa/epidemiologiaRESUMO
Hepatitis C virus (HCV) Core Antigen (HCVAg) and HCV-RNA were tested in 962 plasma/serum samples from 180 patients during Direct Antiviral Agents (DAAs) treatment and at follow-up. One hundred and eighty individuals were included: 71% carried advanced fibrosis and 43% were treatment-experienced. A Sustained Virological Response (SVR) was achieved in 166/180 (92%) individuals: 96/102 (94.1%) na ve and 70/78 (89.7%) treatment-experienced (p=0.20). The baseline median levels of HCV-RNA and HCVAg were not significantly different between individuals achieving SVR (5.92 x 105 IU/mL, IQR 5.4-6.4, and 3,417 fmol/L, 2,900-3,795) and those without SVR (6.06 x 105 IU/mL, 5.63-6.57, and 3,391 fmol/L, 2,828-4,077). The HCV-RNA vs. HCVAg assays results showed a fair correlation with an overall moderate qualitative agreement (kappa=0.52). Among treatment-failed individuals, at failure 100% of the assays results were positive for both techniques, with HCV-RNA median value 3.09 x 105 IU/mL (2.10-29.09) and HCVAg median value 1570.28 fmol/L (360.15-9317.67). Undetectable HCV-RNA at EOT showed sensitivity 54%, specificity 100%, negative predictive value (NPV) 93% and positive predictive value (PPV) 100%. Undetectable HCVAg at EOT showed sensitivity 74%, specificity 100%, NPV 97% and PPV 100%. The operative and economic advantages of the HCVAg support the alternative use of HCVAg to monitor DAAs treatment outcome.
Assuntos
Hepacivirus , Hepatite C Crônica , Antivirais/uso terapêutico , Quimioterapia Combinada , Hepacivirus/genética , Antígenos da Hepatite C/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Humanos , RNA Viral , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
Autophagy is a catabolic process that is important for maintaining cellular homeostasis. It is also known to possess other functions including protein trafficking and anti-microbial activities. Hepatitis C virus (HCV) is known to co-opt cellular autophagy pathway to promote its own replication. HCV regulates autophagy through multiple mechanisms to control intracellular protein and membrane trafficking to enhance its replication and suppress host innate immune response. In this review, we discuss the current knowledge on the interplay between HCV and autophagy and the crosstalk between HCV-induced autophagy and host innate immune responses.
Assuntos
Autofagia/fisiologia , Hepacivirus/fisiologia , Hepatite C/virologia , Transporte Proteico , Replicação Viral , Membrana Celular/metabolismo , Hepatite C/patologia , Hepatócitos/virologia , Homeostase , Humanos , Imunidade Inata , Microdomínios da Membrana , Mitocôndrias/metabolismo , Mitofagia , RNA Viral/metabolismo , Transdução de SinaisRESUMO
We analyzed post-treatment hepatitis C virus (HCV) RNA levels from 330 subjects who experienced virologic failure in clinical trials of direct-acting antivirals. We demonstrated that 97% had post-treatment Week 12 HCV RNA >10 000 IU/mL, above reported sensitivity limits of novel diagnostic assays being considered for simplified HCV treatment monitoring.
Assuntos
Antivirais , Hepatite C Crônica , Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , RNA Viral , Resposta Viral SustentadaRESUMO
Hepatitis C virus (HCV) non-structural protein NS5A is a multifunctional protein with critical roles in viral replication and assembly. We previously showed that HCV-1b NS5A downregulates viral translation only in the presence of the poly(U/UC) tract in 3'UTR. As NS5A of different HCV genotypes may have different functions or carry out the same functions through genotype-specific mechanisms, we investigated the effect of HCV-2a NS5A on viral translation. We found that HCV-2a NS5A downregulates RNA translation of both HCV-2a and -1b, whereas the effect of HCV-1b NS5A is limited to HCV-1b only. In addition, individual regions of 3'UTR are not required for HCV-2a NS5A to downregulate viral RNA translation. We also found that HCV-2a NS5A inhibits capped mRNA translation. Mapping experiments showed that the translation downregulation by HCV-2a NS5A is predominantly mediated by domain I. Furthermore, we found that the integrity of serine-146 residue plays an important role in translation downregulation by NS5A. Our results increased our understanding on genotype-specific functions of HCV NS5A.
Assuntos
Hepacivirus/genética , Hepacivirus/fisiologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/fisiologia , Regiões 3' não Traduzidas , Linhagem Celular , Regulação para Baixo , Regulação Viral da Expressão Gênica , Genótipo , Hepacivirus/classificação , Hepatite C/virologia , Humanos , Biossíntese de Proteínas , Domínios Proteicos , RNA Viral/genética , RNA Viral/metabolismo , Serina/química , Proteínas não Estruturais Virais/química , Replicação Viral/genética , Replicação Viral/fisiologiaRESUMO
To achieve the ambitious goals of the WHO to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030, innovative approaches are needed to improve the uptake for screening and treatment in people who inject drugs (PWID). Important barriers to care are difficult venous access and the two-step approach in current point-of-care tests, using an HCV antibody screening test followed by a confirmatory HCV RNA test. In this study, we aimed to validate the new GenXpert instrument to diagnose HCV RNA by finger prick. This prospective study was conducted in a cohort of PWID in 6 alcohol/drug clinic sites and 1 outreach project in Belgium between January 2018 and March 2019. Plasma and capillary whole-blood samples were collected by venepuncture and finger prick, respectively. Sensitivity and specificity of the GenXpert system were compared to the gold standard Artus HCV RNA kit. Of 153 participants enrolled, 147 (96.1%) had results of both the GenXpert system and Artus HCV RNA kit available. HCV RNA was detected in 35 of 147 (23.8%) by the Artus HCV RNA kit and in 36 of 147 (24.8%) by the GenXpert. Median quantitative HCV RNA viral load on finger prick was 28 700 IU/mL (IQR 4070-65 875) vs 1 900 000IU/mL (IQR 416,466-2,265,510) on plasma. The GenXpert instrument had a sensitivity of 100% (95% CI 90%-100%) and a specificity of 99.1% (95.1%-99.9%). The overall diagnostic accuracy was 99.3% (96.3%-99.9%). This study validates the excellent performance of the GenXpert instrument to assess HCV RNA in capillary whole blood by finger prick in a PWID cohort.