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1.
BMC Infect Dis ; 24(1): 1054, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333922

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) antibody self-testing (HCVST) may help expand screening access and support HCV elimination efforts. Despite potential benefits, HCVST is not currently implemented in Pakistan. This study aimed to assess the usability and acceptability of HCVST in a high HCV prevalence informal settlement in Karachi, Pakistan. METHODS: We performed a cross-sectional study in a hepatitis C clinic from April through June 2023. Participants were invited to perform a saliva-based HCVST (OraSure Technologies, USA) while following pictorial instructions. A study member evaluated test performance using a standardized checklist and provided verbal support if a step could not be completed. Perceived usability and acceptability were assessed using a semi-structured questionnaire. The HCVST was considered successful if the participant was able to complete all steps and correctly interpret test results. Overall concordance and positive and negative agreement were estimated in comparison with the HCVST result read by the study member (inter-reader concordance and agreement) and result of a second rapid HCV test (Abbott Diagnostics Korea Inc, South Korea) performed by a trained user (inter-operator concordance and agreement). RESULTS: The study included 295 participants of which 97 (32%) were illiterate. In total, 280 (95%, 95% CI 92-97%) HCVSTs were successful. Overall, 38 (13%) people performed the HCVST without verbal assistance, 67 (23%) needed verbal assistance in one step, 190 (64%) in two or more. Assistance was most often needed in managing the test buffer and test reading times. The inter-reader concordance was 96% and inter-operator concordance 93%. Inter-reader and inter-operator positive percent agreement were 84 and 70%, respectively. All participants reported they would use HCVST again and would recommend it to friends and family. CONCLUSION: Saliva-based HCVST was very well accepted in this clinic-based setting. However, many people requested verbal support in several steps, highlighting the need for clear instructions for use and test devices that are simple to use, particularly in low literacy settings. Moderately low positive percent agreement with the results of a rapid test performed by a trained user highlights potential uncertainty in the accuracy of HCVST in the hands of lay users.


Asunto(s)
Hepatitis C , Autoevaluación , Humanos , Pakistán/epidemiología , Masculino , Femenino , Estudios Transversales , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Adulto , Persona de Mediana Edad , Prevalencia , Hepacivirus/aislamiento & purificación , Tamizaje Masivo/métodos , Anticuerpos contra la Hepatitis C/sangre , Aceptación de la Atención de Salud/estadística & datos numéricos , Población Urbana , Encuestas y Cuestionarios , Adulto Joven , Saliva/virología
2.
BMC Infect Dis ; 19(1): 128, 2019 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-30732573

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. Prevalence of HCV in homeless populations ranges from 3.9 to 36.2%. The HepCheck study sought to investigate and establish the characterisation of HCV burden among individuals who attended an intensified screening programme for HCV in homeless services in Dublin, Ireland. METHODS: The HepCheck study was conducted as part of a larger European wide initiative called HepCare Europe. The study consisted of three phases; 1) all subjects completed a short survey and were offered a rapid oral HCV test; 2) a convenience sample of HCV positive participants from phase 1 were selected to complete a survey on health and social risk factors and 3) subjects were tracked along the referral pathway to identify whether they were referred to a specialist clinic, attended the specialist clinic, were assessed for cirrhosis by transient elastography (Fibroscan) and were treated for HCV. RESULTS: Five hundred ninety-seven individuals were offered HCV screening, 73% were male and 63% reported having had a previous HCV screening. We screened 538 (90%) of those offered screening, with 37% testing positive. Among those who tested positive, 112 (56%) were 'new positives' and 44% were 'known positives'. Undiagnosed HCV was prevalent in 19% of the study sample. Active past 30-day drug use was common, along with attendance for drug treatment. Unstable accommodation was the most common barrier to attending specialist appointments and accessing treatment. Depression and anxiety, dental problems and respiratory conditions were common reported health problems. Forty-six subjects were referred to specialised services and two subjects completed HCV treatment. CONCLUSIONS: This study demonstrates that the current hospital-based model of care is inadequate in addressing the specific needs of a homeless population and emphasises the need for a community-based treatment approach. Findings are intended to inform HepCare Europe in their development of a community-based model of care in order to engage with homeless individuals with multiple co-morbidities including substance abuse, who are affected by or infected with HCV.


Asunto(s)
Atención a la Salud/métodos , Hepatitis C/diagnóstico , Personas con Mala Vivienda , Adulto , Europa (Continente) , Femenino , Hepacivirus/inmunología , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Antígenos de la Hepatitis C/sangre , Humanos , Irlanda/epidemiología , Masculino , Tamizaje Masivo , Prevalencia , Encuestas y Cuestionarios
3.
J Gastroenterol Hepatol ; 34(9): 1641-1647, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30707777

RESUMEN

BACKGROUND: Chronic hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs but is often undiagnosed. The treatment paradigm for HCV patients has been changing since the availability of direct-acting antiviral (DAA) treatment. We aimed to evaluate the change in treatment paradigm of people who previously injected drugs (ex-PWID) in Hong Kong before and after the availability of DAA. METHOD: Consecutive ex-PWID referred from various nongovernmental organizations attended education talks at rehabilitation centers and received point-of-care rapid test for HCV antibody (anti-HCV) at the same session. Subjects tested positive for anti-HCV were invited to undergo further assessment. Afterwards, the patients were referred to the regional hospitals for follow-up and/or treatment. RESULTS: Three hundred sixty-five ex-PWID received HCV rapid test; 268 (73.4%) were found to be anti-HCV positive. Among these 268 HCV-positive ex-PWID, 234 (87.3%) attended the assessment session (mean age 52 years, 90.2% male, 45.5% genotype 1b, 41.1% genotype 6a, and median liver stiffness 5.9 kPa); 187 (69.8%) attended follow-up visits at regional hospitals. Seventy-one patients received antiviral treatment for HCV; 69 first received peginterferon and ribavirin (PegIFN/RBV), whereas 10 patients (eight PegIFN/RBV-treated patients) received DAA treatment. Fifty-two patients achieved sustained virologic response at 12 or 24 weeks. Treatment uptake rates of PegIFN/RBV and DAA treatment in the pre-DAA versus post-DAA era were 22.3% versus 48.5% and 0% versus 15.6%, respectively. CONCLUSIONS: Targeted screening in ex-PWID is effective in identifying patients with HCV infection in the community. To improve treatment uptake, further improvements in the referral system and treatment regimens are needed.


Asunto(s)
Antivirales/uso terapéutico , Consumidores de Drogas , Hepatitis C Crónica/tratamiento farmacológico , Interferón alfa-2/uso terapéutico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/transmisión , Hong Kong/epidemiología , Humanos , Interferón alfa-2/efectos adversos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Prevalencia , Evaluación de Programas y Proyectos de Salud , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Factores de Riesgo , Respuesta Virológica Sostenida , Factores de Tiempo , Resultado del Tratamiento
4.
Euro Surveill ; 24(14)2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30968825

RESUMEN

IntroductionData on chronic hepatitis C (HCV) infection prevalence in European prisons are incomplete and impact the public health opportunity that incarceration provides.AimsWe aimed to estimate the seroprevalence of untreated chronic HCV infection and to identify associated risk factors in an Irish male prison.MethodsWe conducted a cross-sectional study involving a researcher-administered questionnaire, review of medical records and HCV serology.ResultsOf 422 prisoners (78.0% of the study population) who participated in the study, 298 (70.6%) completed the questionnaire and 403 (95.5%) were tested for HCV antibodies. Of those tested, 92 (22.8%) were HCV antibody-positive, and of those, 53 (57.6%) were HCV RNA-positive, 23 (25.0%) had spontaneous clearance, 16 (17.4%) had a sustained viral response, 10 (11.0%) were co-infected with HIV and six (6.0%) with HBV. The untreated chronic HCV seroprevalence estimate was 13.1% and the seroprevalence of HCV among prisoners with a history of injecting drug use (IDU) was 79.7%. Risk factors significantly associated with past HCV infection were IDU (p < 0.0001), having received a prison tattoo (p < 0.0001) or a non-sterile community tattoo (p < 0.0001), sharing needles and other drug-taking paraphernalia (p < 0.0001). Small numbers of prisoners had a history of sharing razors (n=10; 3.4%) and toothbrushes (n=3; 1.0%) while incarcerated. On multivariable analysis, history of receiving a non-sterile community tattoo was the only significant risk factor associated with HCV acquisition (after IDU was removed from the model) (p = 0.005, ß = 0.468).ConclusionThe level of untreated chronic HCV infection in Irish prisons is high, with IDU the main associated risk.


Asunto(s)
Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Prisioneros/estadística & datos numéricos , Prisiones , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Estudios Transversales , Consumidores de Drogas , Hepacivirus/inmunología , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/análisis , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Estudios Seroepidemiológicos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Encuestas y Cuestionarios , Adulto Joven
5.
Pak J Pharm Sci ; 31(1): 83-87, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29348088

RESUMEN

The current study was designed in order to elucidate the most sensitive method for daily practice as well as to evaluate the risk factors for HCV infection associated with blood transfusion in District Peshawar. A total of 1400 healthy volunteer blood donors were tested for Anti-HCV. A questionnaire was used to evaluate the risk factors. Initial testing of all blood samples was done by Immuno Chromatographic Technique (ICT) and confirmed by micro particle enzyme immunoassay (MEIA) and Enzyme Linked Immunosorbent Assay (ELISA). The comparison among ICT, ELISA and MEIA techniques was also evaluated for the purpose of sensitivity. Among 1400 blood donors, 26 (1.85%) cases were found positive for Anti-HCV. These 26 cases were positive on MEIA, 16 individuals were positive on ELISA while 14 were positive on ICT. These 26 cases had different histories of dental treatment (50%), traveled abroad (23.07%), surgery (11.53%), blood transfusion (7.69%) and unknown reason (7.69%). Among all these different histories of dental treatment and blood transfusion were the main risk factors for HCV infection. The results revealed that MEIA is a quick and reliable technique for routine screening of blood donors particularly for controlling the spread of HCV.


Asunto(s)
Donantes de Sangre , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/sangre , Hepatitis C/epidemiología , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Pakistán/epidemiología , Prevalencia , Factores de Riesgo , Sensibilidad y Especificidad
6.
J Med Virol ; 89(8): 1435-1441, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28165155

RESUMEN

The use of saliva and dried blood spots (DBS) could increase access to HCV diagnosis for high-risk populations, such as HIV-infected individuals, but the performance of these assays has not been well established in this group. This study aims to evaluate HIV status, particularly TCD4+ cell count and viral load, in the performance of anti-HCV testing using DBS and saliva. A total of 961 individuals classified as HCV+, HIV+, or HIV/HCV+, as well as negative controls, donated serum, DBS, and saliva samples for anti-HCV testing using a commercial enzyme immunoassay. Sample volume was modified for DBS and saliva, and an ROC curve was used for cut-off determination in saliva. Anti-HCV sensitivities were greater than 93% using DBS and saliva in the HCV+ group, while they were 83.3% and 95.6% for HCV/HIV+ individuals for DBS and saliva assays, respectively. Specificity varied from 91.7% to 100% using saliva and DBS in HIV monoinfected and control subjects. When only anti-HCV/HCV RNA+ serum samples, that is, true positives, were considered, the sensitivities were 98.3% and 100% for DBS and saliva, respectively, in the HCV+ group and 91.6% and 94.8% for DBS and saliva, respectively, in the HIV/HCV+ group. High absorbance values were observed among those presenting with HCV RNA in serum and low HIV viral load (less than 50 copies/mL). In conclusion, DBS and saliva samples could be used for anti-HCV detection, particularly to identify active HCV cases, but low sensitivity was observed for anti-HCV testing using DBS in the HIV/HCV+ group.


Asunto(s)
Sangre/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Infecciones por VIH/complicaciones , Anticuerpos contra la Hepatitis C/análisis , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/diagnóstico , Saliva/inmunología , Adulto , Anciano , Recuento de Linfocito CD4 , Desecación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Manejo de Especímenes/métodos , Encuestas y Cuestionarios , Carga Viral
7.
J Gen Virol ; 97(8): 1865-1876, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27147296

RESUMEN

An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and class II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g cm-3. The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8+ T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huh7 cells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8+ T-cell responses and will have important implications for the development of a preventative vaccine for HCV.


Asunto(s)
Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Linfocitos T/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Línea Celular , Células Cultivadas , Hepacivirus/genética , Hepatocitos/virología , Humanos , Ratones Endogámicos BALB C , Ratones Transgénicos , Microscopía Electrónica , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/genética , Vacunas de Partículas Similares a Virus/aislamiento & purificación , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/inmunología , Proteínas del Núcleo Viral/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Virosomas/genética , Virosomas/inmunología , Virosomas/metabolismo , Virosomas/ultraestructura
8.
Epidemiol Infect ; 144(3): 627-34, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26178148

RESUMEN

To estimate HCV seroprevalence in subpopulations of women delivering live-born infants in the North Thames region in England in 2012, an unlinked anonymous (UA) cross-sectional survey of neonatal dried blood spot samples was conducted. Data were available from 31467 samples from live-born infants received by the North Thames screening laboratory. Thirty neonatal samples had HCV antibodies, corresponding to a maternal seroprevalence of 0·095% (95% confidence interval 0·067-0·136). Estimated HCV seroprevalences in women born in Eastern Europe, Southern Asia and the UK were 0·366%, 0·162% and 0·019%, respectively. For women born in Eastern Europe seroprevalence was highest in those aged around 27 years, while in women born in the UK and Asia-Pacific region, seroprevalence increased significantly with age. HCV seroprevalence in UK-born women whose infant's father was also UK-born was 0·016%. One of the 30 HCV-seropositive women was HIV-1 seropositive. Estimated HCV seroprevalence for women delivering live-born infants in North Thames in 2012 (0·095%) was significantly lower than that reported in an earlier UA survey in 1997-1998 (0·191%). Data indicate that the cohort of UK-born HCV-seropositive women is ageing and that, in this area of England, most perinatally HCV-exposed infants were born to women themselves born in Southern Asia or Eastern Europe.


Asunto(s)
Sangre Fetal/inmunología , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/etnología , Nacimiento Vivo/etnología , Complicaciones Infecciosas del Embarazo/etnología , Adulto , Factores de Edad , Asia/etnología , Inglaterra/epidemiología , Europa Oriental/etnología , Femenino , Hepatitis C/sangre , Humanos , Maloclusión , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/virología , Prevalencia , Estudios Seroepidemiológicos , Adulto Joven
9.
J Virol ; 88(10): 5502-10, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24599994

RESUMEN

UNLABELLED: Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8+ and CD4+ T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to-cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone. IMPORTANCE: HCV infection is a major health problem. Despite the availability of new directly acting antiviral agents for treating chronic infection, an affordable preventive vaccine provides the best long-term goal for controlling the global epidemic. This report describes a new anti-HCV vaccine targeting the envelope viral proteins based on adenovirus vector and protein in adjuvant. Rodents primed with the adenovirus vaccine and boosted with the adjuvanted protein developed cross-neutralizing antibodies and potent T cell responses that surpassed immune responses achieved with either vaccine component alone. If combined with the adenovirus vaccine targeting the HCV NS antigens now under clinical testing, this new vaccine might lead to a stronger and broader immune response and to a more effective vaccine to prevent HCV infection. Importantly, the described approach represents a valuable strategy for other infectious diseases in which both T and B cell responses are essential for protection.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Linfocitos T/inmunología , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología , Adenoviridae/genética , Adyuvantes Inmunológicos/administración & dosificación , Animales , Femenino , Vectores Genéticos , Cobayas , Hepacivirus/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Polisorbatos/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Escualeno/administración & dosificación , Vacunación/métodos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Proteínas del Envoltorio Viral/genética , Vacunas Virales/administración & dosificación , Vacunas Virales/genética
10.
Virol J ; 12: 204, 2015 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-26626263

RESUMEN

BACKGROUND: Viral hepatitis is a life-threatening liver disease that has become important public health issue in developing countries including Ethiopia. This study was undertaken to determine the seroprevalence of HBsAgs and anti-HCV antibodies and what socio-demographic factors are associated with sero-positivity of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections among pregnant women attending maternity ward of Felege Hiwot Referral Hospital, northwest, Ethiopia. METHODS: Hospital based cross-sectional study was conducted from November 2013 to January 2014. Blood samples were randomly collected from 384 pregnant women. Data on socio-demographic characteristics, obstetric and potential risk factors were collected using semi-structured questionnaire. Chromatographic kits were used to detect the presence of HBsAg and antibodies against HCV in serum samples of the studied subjects. Chi-square test was used for assessing the association between socio-demographic variables and HBV and HCV status. Logistic regression analysis was done to determine the strength of association between risk factors and HBV or HCV infection. P-values less than 0.05 were considered as significant. RESULTS: Seroprevalnce of hepatitis B and C virus infections were found to be 4.4 and 0.26 %, respectively. None of the pregnant women were co-infected by these two viruses. Amongst the potential risk factors, previous history of dental procedure (AOR = 4.104, CI = 1.276-13.201, P = 0.018), house hold contact (AOR = 5.475, CI = 1.472-20.368, P = 0.011), multiple sexual exposure (AOR = 5.041, CI = 1.580-16.076, P = 0.006), and delivery at traditional birth attendants (AOR = 4.100, CI = 0.195-86.129, P = 0.024) were significantly associated with and important predictors of hepatitis B infection. CONCLUSIONS: This study found an intermediate endemicity (4.4 %) of HBV infection in pregnant women whereas seroprevalence of anti-HCV antibody was very small, but this needs to be confirmed by other similar studies with larger sample size. Thus, scaling up of the screening of pregnant women for HBV and HCV infections and provision of health education about the risk factors, the mode of transmissions and prevention is recommended.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Estudios Transversales , Demografía , Etiopía/epidemiología , Femenino , Hospitales , Humanos , Embarazo , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Socioeconómicos , Adulto Joven
11.
BMC Public Health ; 15: 928, 2015 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-26386815

RESUMEN

BACKGROUND: Fuyu city in China has a high prevalence of hepatitis C virus (HCV) infection resulting in a high morbidity and mortality from chronic liver disease and hepatocellular carcinoma. This study was conducted to identify the risk factors for HCV infection in Fuyu city. METHODS: Recruitment of study subjects involved a cross-sectional survey using non-random, convenience sampling. Information on demographic variables, risk factors for HCV infection, clinical manifestations, behavioral practices and family history was collected by administering a questionnaire. Anti-HCV antibody was detected using Abbott ARCHITECT i2000SR. HCV infection was confirmed by HCV-RNA testing by the Roche Taqman HCV test. Univariate and multivariate analyses were performed to identify the factors associated with HCV infection. RESULTS: Out of 3,228 persons that participated in the survey, 3,219 were enrolled in the study. The prevalence of HCV infection was 42.1 % (1355/3219). Among 734 patients with chronic HCV infection whose HCV-RNA genotyping was performed, genotype 1b was the most common (58.0 %), followed by genotype 2a (40.2 %), while co-infection with genotypes 1b and 2a was detected in 1.8 % of the subjects. On univariate analysis, male gender, older age, parenteral caffeinum natrio-benzoicum and share syringes (PCNBSS), and nine other factors were significantly associated with HCV infection. After adjusting for potential confounders, male gender, old age, cigarette smoking, lower education level, history of blood transfusion, blood donation, prior dental surgery, and PCNBSS were found to be independently associated with HCV infection. CONCLUSIONS: The prevalence of HCV infection is likely to be high among residents in Fuyu and we observed that genotypes 1b and 2a dominated in the city. Our findings support the hypothesis that PCNBSS which became endemic in Fuyu city during 1970s-1980s is strongly associated with HCV positivity.


Asunto(s)
Hepacivirus/genética , Hepatitis C/epidemiología , Compartición de Agujas , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Factores de Edad , Cafeína/administración & dosificación , China/epidemiología , Coinfección/epidemiología , Estudios Transversales , Femenino , Genotipo , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Benzoato de Sodio/administración & dosificación
12.
J Viral Hepat ; 21(7): 458-65, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24750327

RESUMEN

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Antivirales/uso terapéutico , Hepatitis C Crónica/terapia , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Polisorbatos/administración & dosificación , Ribavirina/uso terapéutico , Escualeno/administración & dosificación , Vacunas contra Hepatitis Viral/inmunología , Adyuvantes Inmunológicos/efectos adversos , Anticuerpos Neutralizantes/sangre , Linfocitos T CD4-Positivos/inmunología , Proliferación Celular , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Inyecciones Intramusculares , Polisorbatos/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Escualeno/efectos adversos , Resultado del Tratamiento , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Vacunas contra Hepatitis Viral/administración & dosificación , Vacunas contra Hepatitis Viral/efectos adversos , Vacunas contra Hepatitis Viral/genética , Carga Viral
13.
J Med Virol ; 86(4): 707-12, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24415442

RESUMEN

Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.


Asunto(s)
Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interleucinas/genética , Adulto , Antivirales/uso terapéutico , Secuencia de Bases , Biomarcadores/sangre , Quimioterapia Combinada , Femenino , Genotipo , Anticuerpos contra la Hepatitis C/sangre , Humanos , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Análisis de Secuencia de ADN , Resultado del Tratamiento , Carga Viral
14.
J Med Virol ; 85(9): 1542-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23780703

RESUMEN

Hepatitis C is a global health problem with a worldwide prevalence of about 3% (around 170 million people). Hepatitis C virus (HCV) is major concern in the Maghreb countries, Algeria, Libya, Mauritania, Morocco, and Tunisia, but no detailed description of its epidemiology in the region is available. In the present review, a systematic search was undertaken covering HCV data available in peer-reviewed databases as well as institutional reports and regional conference meeting abstracts from the Maghreb countries. Reports written in English and French were included in this analysis. Estimates of national and regional prevalence of HCV infection (based on anti-HCV antibody) and of the size of patient populations were performed. In addition, the molecular features of the circulating viral strains in the region are discussed. A substantial proportion, 1.2-1.9% of the Maghreb inhabitants, have anti-HCV antibodies. Genotype 1b predominates among viral strains in all countries except in Libya, where genotype 4 is dominant as in neighboring Egypt. This epidemiological situation is of significant concern, and requires urgent, broad, and active intervention for the prevention and control of HCV. More specifically, the application of state-of-the-art hygiene procedures and rigorous controls in medical disciplines such as hemodialysis, transfusion, endoscopic procedures, and dentistry is necessary to reduce significantly the number of new infections in the region.


Asunto(s)
Hepatitis C/epidemiología , África del Norte/epidemiología , Variación Genética , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Prevalencia
15.
J Med Virol ; 85(10): 1724-33, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23813472

RESUMEN

The epidemiological and clinical features of hepatitis C virus (HCV) infection in South Korea were examined in a prospective, multicenter cohort study that included 1,173 adult patients with positive results for anti-HCV antibody who completed a questionnaire survey on the risk factors for HCV infection from January 2007 to December 2011 at five university hospitals. The HCV cohort had a mean age of 55.4 years with 48.3% men, and diagnostic categories of acute hepatitis (n = 63, 5.3%), past infection (n = 37, 3.2%), chronic hepatitis (n = 777, 66.2%), cirrhosis of the liver (n = 179, 15.3%), and hepatocellular carcinoma (n = 117, 10.0%). The major HCV genotypes were genotype 1 (52.7%) and genotype 2 (45.3%). Liver biopsy was performed in 301 patients (25.7%), and 42.8% of the subjects received antiviral therapy against HCV. The behavioral risk factors possibly related to HCV infection were intravenous drug use (5%), needle stick injury (7%), blood transfusion before 1995 (19%), sexual relationship with more than three partners (28%), piercings (35%), tattoos (36%), surgery (43%), acupuncture (83%), diagnostic endoscopy (85%), and dental procedures (93%). Age, intravenous drug use, needle stick injury, transfusion before 1995, and tattoos were the independent risk factors of HCV infection.


Asunto(s)
Hepatitis C/epidemiología , Hepatitis C/patología , Adulto , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Hospitales Universitarios , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios
16.
Haemophilia ; 19(6): 847-52, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23738855

RESUMEN

In Australia prior to 1992, many patients with bleeding disorders were exposed to hepatitis C through blood products. However, the incidence, complications and response to treatment of chronic hepatitis C (CHC) in this population are poorly characterized. The aim of this study was to examine the prevalence of CHC and response to treatment in an Australian bleeding disorders population. Demographic data, virological data and liver disease status from these 700 patients with inherited bleeding disorders were analysed. Of these 700 patients, 424 (61%) had been tested for CHC infection and 219 (52%) were hepatitis C antibody positive, with the prevalence approaching 100% in patients with severe bleeding disorders. Of 219 patients, 73 (33%) had received treatment for their infection with a response rate of 33/73 (45%) across all genotypes. Of 219 patients, 34 (16%) had spontaneous viral clearance. When measured with transient elastography, 44/98 (45%) patients with CHC had significant liver fibrosis and 15/98 (15%) had liver cirrhosis. Of 130 patients, 38 (29%) with CHC infection had no evidence of follow-up with an appropriate clinician in the past 2 years. This study demonstrates that testing for CHC in this population is incomplete and treatment rates are low. Given the substantial morbidity and mortality associated with CHC and new therapeutic options becoming available, it seems important to reengage patients to diagnose, offer treatment and monitor this infection.


Asunto(s)
Trastornos de la Coagulación Sanguínea/complicaciones , Hepatitis C Crónica/epidemiología , Reacción a la Transfusión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Australia , Transfusión Sanguínea/estadística & datos numéricos , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Prevalencia , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Ribavirina/uso terapéutico , Adulto Joven
17.
Clin Exp Nephrol ; 17(1): 115-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22814955

RESUMEN

BACKGROUND: Hepatitis C is the most frequently encountered hepatic disease in dialysis patients. Data related to pegylated interferon alfa-2a (Peg-IFN-α-2a) use in hemodialysis patients with hepatitis C virus (HCV) are limited. The aim of this study was to evaluate the efficacy of Peg-IFN-α-2a among these patients. METHODS: Forty-one IFN-naive hemodialysis patients infected by HCV were assessed. All patients had positive anti-HCV antibody and positive HCV-RNA. Peg-IFN-α-2a 135 mcg/week was given for 48 weeks. Biochemical and virological responses were evaluated at treatment weeks 12, 24, 48, and 72. RESULTS: Thirty-eight of the 41 patients who completed the treatment enrolled in the study. Mean age of the 38 patients was 38.1 (range 23-65) years, and the study group was predominantly male (65.8 %). There was no statistically significant difference in mean age, gender, mean duration of hemodialysis, HCV infection, patient numbers with normal alanine aminotransferase (ALT) values and mean ALT, platelet, and HCV-RNA values between patients who achieved sustained virological response (SVR) and those who did not. Only the Knodell histology activity index correlated with SVR (P = 0.048). Biochemical and virological response rates at the 12th week (early response) were 94.7 % and 60.5 %, respectively. The 34 (89.5 %) patients achieved biochemical response at the end of therapy (48th week); 24 (63.2 %) remained HCV-RNA negative. At the 72nd week, biochemical and virological response rates were 84.2 % and 50 %, respectively. DISCUSSION: According to results of this study, patients achieved good sustained viral and biochemical response rates with Peg-IFN-α-2a treatment. Histology activity index may be a predictor for SVR; but large randomized controlled trials are needed. Weekly 135 mcg dose of Peg-IFN-α-2a for 48 weeks is an effective treatment in HCV-infected hemodialysis patients.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Diálisis Renal , Adulto , Anciano , Alanina Transaminasa/sangre , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Adulto Joven
18.
Ann Hepatol ; 12(2): 248-55, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23396736

RESUMEN

BACKGROUND AND AIM: The commonly accepted treatment for hepatitis C virus (HCV) infection, pegylated interferon alpha (PEG INF-alpha) and ribavirin, leads to 50-60% of sustained virological response (SVR). On the other hand, pentoxifylline (PTX) possesses antiviral and hepatoprotector properties. AIM: To investigate whether the addition of PTX to conventional hepatitis C treatment increases SVR. MATERIAL AND METHODS: Seventy two patients of both genders were studied in a randomized fashion; the diagnosis of chronic HCV infection was made according to clinical and laboratory criteria and histopathologically classified according to METAVIR scoring system criteria. HCV viral load was tested by PCR, baseline, and after 6 months of treatment, as well as anti-HCV, anti-hepatitis B virus , and anti-human immunodeficiency virus antibodies by enzyme-linked immunosorbent assay. During 48 weeks, control group patients were treated with PEG INF-alpha- 2a plus ribavirin. PTX was administered to Experimental Group patients prior to the treatment. RESULTS: Demographic data were similar in both groups. Experimental- and control-group subjects were at F2 and F3 states according to the METAVIR classification. The most common HCV genotypes were 1a and 1b (39% in the control group in each case, and 42% in the experimental group in each case). At the end of the study, hepatic enzymes and viral load decreased in both groups to similar values. SVR in the experimental group increased significantly (p < 0.05) when compared with standard therapy alone. CONCLUSION: Addition of PTX to conventional chronic hepatitis C treatment may increase the percentage of patients with SVR.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Pentoxifilina/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Antivirales/efectos adversos , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico , Humanos , Interferón-alfa/efectos adversos , Masculino , México , Persona de Mediana Edad , Pentoxifilina/efectos adversos , Proyectos Piloto , Polietilenglicoles/efectos adversos , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
19.
BMC Public Health ; 13: 50, 2013 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-23331910

RESUMEN

BACKGROUND: Viral hepatitis is a serious public health problem affecting billions of people globally. Limited information is available on this issue in Morocco. This cross-sectional study was undertaken with the aim of determining the seroprevalence and risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) among the general population and among blood donors. METHODS: Blood samples from volunteers, have been screened with ELISA tests for detecting the hepatitis-B surface antigen (HBsAg) and anti-HCV. Within the seroreactive patients for HCV in the general population, RT-PCR was performed by the Cobas Ampliprep/Cobas Amplicor. RESULTS: HCV and HBV-seropositivity was documented in 1.58% and 1.81% out of 41269 and 23578 participants respectively from the general population. Two patients were found to be co-infected. HCV-RNA was detected by PCR in 70.9% of the 195 anti-HCV positive subjects. The anti-HCV prevalence was not different among males and females (P = 0.3). It increased with age; the highest prevalence was observed among subjects with >50 years old (3.12%). Various risk factors for acquiring HCV infection were identified; age, dental treatment, use of glass syringes and surgical history. In addition to these factors, gender and sexual risk behaviors were found to be associated with higher prevalence of hepatitis B. The HBV positivity was significantly higher among males than females participants in all age groups (P < 0.01). The peak was noticed among males aged 30-49 years (2.4%). None of the 152 persons younger than 20 years had HBsAg or anti-HCV. The prevalence of anti-HCV and HBsAg among 169605 blood donors was 0.62% and 0.96% respectively. CONCLUSIONS: Our study provided much important information concerning hepatitis B and C prevalence and risk factors; it confirmed the intermediate endemicity for HCV infection and pointed to a decreasing trend of HBV incidence, which might reclassify Morocco in low HBV endemicity area. This could be attributed primarily to the universal HBV vaccination among infants and healthcare workers over the past 13 years. HCV and HBV infections in the present survey were mainly associated with nosocomial exposures. Prevention and control of HBV infection are needed to reduce HBV transmission between adults.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Diálisis Renal/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Infección Hospitalaria/transmisión , Estudios Transversales , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Marruecos/epidemiología , Vigilancia de la Población , Prevalencia , Factores de Riesgo , Adulto Joven
20.
J Viral Hepat ; 19(3): 182-8, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22329372

RESUMEN

Hepatitis C virus (HCV) infection is a major cause for chronic liver disease and hepatocellular carcinoma. The HCV-ARF/core+1 protein is an alternative product of HCV core-encoding sequence of unknown biological function. Highly purified HCV core and ARF/core+1 recombinant proteins from HCV genotype 1a and HCV-ARF/core+1 recombinant protein from HCV genotype 3a were expressed in Escherichia coli. Using an enzyme-linked immunosorbent assay, we assessed the prevalence of anti-ARF/core+1 antibodies in 90 chronic hepatitis C patients infected with HCV genotypes 1a/1b or 3a, treated with pegylated interferon (Peg-IFN-a-2a) plus ribavirin. Samples derived from 92 healthy blood donors were used as negative controls. All HCV-RNA-positive serum samples reacted with core 1a antigen, while 15 (37.5%) of 40 and 14 (28%) of 50 patients infected with HCV-1a/1b and HCV-3a, respectively, were found to have anti-ARF/core+1 antibodies into their serum before treatment initiation. These antibodies were persistently present during treatment follow-up and linked to elevated levels of HCV-RNA at baseline.


Asunto(s)
Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/inmunología , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Proteínas del Núcleo Viral/inmunología , Adulto , Anciano , Antivirales/uso terapéutico , Quimioterapia Combinada , Escherichia coli/genética , Escherichia coli/metabolismo , Femenino , Hepacivirus/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Proteínas del Núcleo Viral/genética , Adulto Joven
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