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Single-nucleotide polymorphism in APOBEC3C (resulting in a serine to isoleucine in position 188) is present in approximately 10% of African populations and greatly enhances restriction against human immunodeficiency virus-1 and simian immunodeficiency virus by improving dimerization and DNA processivity of the enzyme. In this study, we demonstrated in culture and in infected patients that hepatitis B virus (HBV) could be edited by APOBEC3CS188I. Using next-generation sequencing, we demonstrated that APOBEC3CS188I led to enhanced editing activity in 5'TpCpAâ5'TpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.
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Citidina Desaminasa , Genoma Viral , Virus de la Hepatitis B , Citidina Desaminasa/genética , Hepatitis B/genética , Virus de la Hepatitis B/genética , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Hepatitis C virus (HCV) infection is known to be an important risk factor for hepatocellular carcinoma (HCC) in Cameroon. However, the effect of HCV-related factors on HCC development still remains unknown in the Central Africa. In this study, we investigated the role of HCV genotypes and core mutations in HCC development in Cameroonian patients. METHODS: A case-control study was conducted using patients with HCV-related HCC and matched controls individuals with chronic HCV infection but without HCC. HCV genotypes and mutations were determined using a hemi-nested amplification and sequencing analysis focus on the core and NS5B HCV regions. RESULTS: We identify HCV genotype 1, 2 and 4 in both groups. Interestingly, genotype 4 was significantly more prevalent in HCC patients (53.3%). Overall, distribution of genotypes was very different between cases and controls (P = 4.2 E-7). The risk factors analysis showed that infection with HCV-4 is strongly associated with HCC development with odd ratio, 95% confidence interval and p-values of 7.4 (95% CI: 2.08-26.6; P = .001). Furthermore, the risk of developing HCC increased even more significantly in case of infection with HCV subtype 4f with the odd ratio of 20.8 (95% CI, 4.1-66.8; P < .001). Mutations K10R, T72E, K74R and G77A were significantly more frequent in patients with HCC. Remarkably, HCV-4f isolates from HCC patients carried significantly more mutations when compared to controls with HCV-4f or others genotypes (P = .0001). CONCLUSIONS: Our results indicate that patients infected with HCV-4f or with selected variants affecting HCV core gene are at increased risk to develop HCC.
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Carcinoma Hepatocelular/virología , Hepacivirus/genética , Hepatitis C , Neoplasias Hepáticas/virología , Camerún , Estudios de Casos y Controles , Genotipo , Hepatitis C/virología , Humanos , MutaciónRESUMEN
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. HEV infection is self-limiting, but fulminant hepatitis may occur with higher mortality rates. The aim of this study was to determine the seroprevalence of the HEV in three different populations in Cameroon and to assess alimentary risk factors of infection. A total of 903 individuals including 450 elderly people, 183 pregnant women, and 270 HIV-infected patients were enrolled during 2009-2015. All sera obtained were tested for the presence of anti-HEV antibodies with commercial enzyme-linked immunosorbent assay kits. The association between initial anti-HEV status and potential risk factors was assessed. Out of the 903 samples, 22.0% (199/903) were positives for anti-HEV immunoglobulin M (IgM), 5.8% (52/903) for anti-HEV IgG, and 3.5% (32/903) for both. The seropositivity for IgM was 7.0%, 13.1%, and 34.7%; meanwhile, the seropositivity for immunoglobulin G was 8.5%, 3.3%, and 5.1%, in HIV-infected patients, pregnant women, and the elderly population, respectively. Both antibodies were detected simultaneously in 2.2%, 1.6%, and 5.1% in HIV-infected patients, pregnant women, and the elderly population, respectively. No risk factors were significantly associated with HEV infection in these populations. This study showed a high prevalence of anti-HEV antibodies in three different populations in Cameroon.
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Infecciones por VIH/epidemiología , Anticuerpos Antihepatitis/sangre , Hepatitis E/epidemiología , Adulto , Anciano , Camerún/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/virología , Hepatitis E/sangre , Virus de la Hepatitis E , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Embarazo , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: Current HCV treatments are genotype specific although potential pan-genotype treatments have recently been described. Therefore, genotyping is an essential tool for the therapeutic management of HCV infection and a variety of technologies have been developed for HCV genotypes determination. Sequences analysis of HCV sub-genomic regions is considered as gold standard and is widely used for HCV genotyping. Here, we compared HCV genotyping using core and NS5B regions in routine practice in HCV-positive Cameroonian patients. METHODS: All plasma samples received at Centre Pasteur of Cameroon (CPC) in 2016 for HCV genotyping were included. Viral loads were determined using the Abbott Real Time assay. Further, genotyping was based on the amplification and sequencing of core and NS5B regions following by phylogenetic analysis of corresponding sequences. RESULTS: A total of 369 samples were received during the study period with high viral load values (median: 930,952 IU/ml; IQR: 281,833-2,861,179). Positive amplification was obtained in at least one genomic region (core or NS5B) for all the samples with similar amplification rate in the two genomic regions (p = 0.34). Phylogenetic analysis showed that among the 369 samples, 146 (39.6%) were classified as genotype 4, 132 (35.8%) as genotype 1, 89 (24.1%) as genotype 2, in both core and NS5B regions. Interestingly, for two samples (0.54%) discordant genotypes were obtained in both regions with the core region classified as genotype 4 while the NS5B was identified as genotype 1 indicating the presence of putative HCV recombinant virus or multiple infections in these samples. Discrimination of HCV subtypes was most likely possible with NS5B compared to core region. CONCLUSIONS: We found high amplification rates of HCV in both core and NS5B regions, and a good concordance was obtained at genotype level using both regions except for two samples where putative 1-4 recombinants/multiple infections were detected. Therefore, HCV genotyping based on at least two genomic regions could help to identify putative recombinants and improve therapeutic management of HCV infection.
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Técnicas de Genotipaje , Hepacivirus/genética , Hepatitis C/virología , Proteínas del Núcleo Viral/genética , Proteínas no Estructurales Virales/genética , Anciano , Camerún , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Análisis de Secuencia de ADN , Carga ViralRESUMEN
We screened hepatitis E from 15 species of non-human primates. Anti-HEV IgG was detected in 11.1% (1/9) Mandrillus sphinx, 14.3% (2/14) Gorilla gorilla, 5.9% (4/67) pan troglodytes and 8.7% (2/23) Mandrillus leucophaeus, whereas anti-HEV IgM was detected in 1.5% (1/18) papio Anubis, 28.6% (2/7) Cercocebus agilis and 1.5% (1/67) pan troglodyte.
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Anticuerpos Antivirales/sangre , Enfermedades del Simio Antropoideo/virología , Cercopithecidae , Gorilla gorilla , Hepatitis E/veterinaria , Enfermedades de los Monos/virología , Pan troglodytes , Animales , Camerún , Hepatitis E/virología , Virus de la Hepatitis ERESUMEN
Background: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among the general population in Conakry, Guinea and Yaounde, Cameroon after the coronavirus disease 2019 Omicron wave. Methods: We conducted population-based, age-stratified seroprevalence surveys in Conakry and Yaounde (May and June 2022). We collected demographic and epidemiologic information and dried blood spot samples that were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies using recombinant nucleocapsid and spike proteins with Luminex technology. Results: Samples were obtained from 1386 and 1425 participants in Guinea and Cameroon, respectively. The overall age-standardized SARS-CoV-2 IgG seroprevalence against spike and nucleocapsid proteins was 71.57% (95% confidence interval [CI], 67.48%-75.33%) in Guinea and 74.71% (95% CI, 71.99%-77.25%) in Cameroon. Seroprevalence increased significantly with age categories. Female participants were more likely than male participants to be seropositive. The seroprevalence in unvaccinated participants was 69.6% (95% CI, 65.5%-73.41%) in Guinea and 74.8% (95% CI, 72.04%-77.38%) in Cameroon. In multivariate analysis, only age, sex, and education were independently associated with seropositivity. Conclusions: These findings show a high community transmission after the different epidemiological waves including Omicron, especially among people aged >40 years. In addition, our results suggest that the spread of SARS-CoV-2 has been underestimated as a significant proportion of the population has already contracted the virus and that vaccine strategies should focus on vulnerable populations.
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BACKGROUND: Occult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects. AIM: To highlight the global prevalence of OCI. METHODS: We performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran's Q-test and the I 2 test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses. RESULTS: The electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I 2 = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa. CONCLUSION: In conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.
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INTRODUCTION: Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa. METHODS: Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses. RESULTS: A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7-105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2-15.6]) and DNA (OR = 8.9; 95% CI = [5.9-13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3-14.0]) and RNA (OR = 16.5; 95% CI = [7.8-34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9-112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3-387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0-13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6-10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4-13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results. CONCLUSIONS: In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed.
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Carcinoma Hepatocelular , Virus de Hepatitis , Hepatitis Viral Humana , Neoplasias Hepáticas , África/epidemiología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/virología , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Factores de RiesgoRESUMEN
This study aimed to assess the global prevalence of occult hepatitis B in blood donors. We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameters. Sources of heterogeneity were explored by subgroup analyses. This study is registered with PROSPERO, number CRD42021252787. We included 82 studies in this meta-analysis. The overall prevalence of OBI was 6.2% (95% CI: 5.4-7.1) in HBsAg negative and anti-HBc positive blood donors. Only sporadic cases of OBI were reported in HBsAg negative and anti-HBc negative blood donors. The overall prevalence of OBI was 0.2% (95% CI: 0.1-0.4) in HBsAg negative blood donors. The prevalence of OBI was generally higher in countries with low-income economic status. The results of this study show that despite routine screening of blood donors for hepatitis B, the transmission of HBV by blood remains possible via OBI and/or a seronegative window period; hence there is a need for active surveillance and foremost easier access to molecular tests for the screening of blood donors before transfusion.
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Hepatitis B Crónica , Hepatitis B , Donantes de Sangre , ADN Viral , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , HumanosRESUMEN
A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1-5.0) and 66.3% (95% CI = 40.0-88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.
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Enterovirus Humano D/aislamiento & purificación , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/mortalidad , Anticuerpos Antivirales , Asma , Enfermedades Virales del Sistema Nervioso Central , Enterovirus Humano D/inmunología , Infecciones por Enterovirus/inmunología , Humanos , Mielitis , Enfermedades Neuromusculares , Prevalencia , Infecciones del Sistema RespiratorioRESUMEN
Point-of-care diagnostics have the potential to increase diagnosis and linkage to care and help reach the WHO targets to eliminate hepatitis C virus (HCV) by 2030. Here, we evaluated the diagnostic accuracy of Genedrive HCV ID assay for the qualitative detection of HCV RNA in decentralized settings in two low- and middle-income countries using fresh plasma specimens from 426 participants. The Abbott RealTime HCV assay was used as the gold standard. Genedrive HCV ID assay was conducted by different users. Users also completed questionnaires to assess the usability of Genedrive. At detection thresholds of 12 IU/mL or 30 IU/mL, 1000 IU/mL, and 2362 IU/mL, the sensitivity was 96.2% (95% CI: 92.7-98.4), 100% (98.2-100), and 100% (98.2-100), respectively; the specificity was 99.5% (95% CI: 97.4-100), 99.5% (97.5-100), and 98.7% (96.1-100), respectively. All genotypes detected using the gold-standard assay were also detected with Genedrive. Users found Genedrive easy to use. Genedrive is a simple and accurate test to confirm chronic HCV infection in decentralized, real-life, resource-limited settings. This novel diagnostic tool could contribute to closing the current gap in HCV diagnosis.
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BACKGROUND: The hepatitis B virus (HBV) infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly. HBV is a blood-borne disease and healthcare workers (HCWs) are a high-risk group because of occupational hazard to patients' blood. Different regions of the world show a highly variable proportion of HCWs infected and/or immunized against HBV. Global data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV control. AIM: To determine the worldwide prevalence of HBV serological markers among HCWs. METHODS: In this systematic review and meta-analyses, we searched PubMed and Excerpta Medica Database (Embase) to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs worldwide. We also manually searched for references of relevant articles. Four independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen (HBsAg), hepatitis e antigen (HBeAg), immunoglobulin M anti-HBc, and anti-HBs. Methodological quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in HCWs. Heterogeneity (I²) was assessed using the χ² test on Cochran's Q statistic and H parameters. Heterogeneity' sources were explored through subgroup and metaregression analyses. This study is registered with PROSPERO, number CRD42019137144. RESULTS: We reviewed 14059 references, out of which 227 studies corresponding to 448 prevalence data among HCWs (224936 HCWs recruited from 1964 to 2019 in 71 countries) were included in this meta-analysis. The pooled seroprevalences of current HBsAg, current HBeAg, and acute HBV infection among HCWs were 2.3% [95% confidence interval (CI): 1.9-2.7], 0.2% (95%CI: 0.0-1.7), and 5.3% (95%CI: 1.4-11.2), respectively. The pooled seroprevalences of total immunity against HBV and immunity acquired by natural HBV infection in HCWs were 56.6% (95%CI: 48.7-63.4) and 9.2% (95%CI: 6.8-11.8), respectively. HBV infection was more prevalent in HCWs in low-income countries, particularly in Africa. The highest immunization rates against HBV in HCWs were recorded in urban areas and in high-income countries including Europe, the Eastern Mediterranean and the Western Pacific. CONCLUSION: New strategies are needed to improve awareness, training, screening, vaccination, post-exposure management and treatment of HBV infection in HCWs, and particularly in low-income regions.
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Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3-37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8-10.8) in humans, 3.2% (1.9-4.6) in rodents, and 0.7% (0.0-2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions.
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Fiebre de Lassa/epidemiología , Fiebre de Lassa/veterinaria , Virus Lassa , África del Sur del Sahara/epidemiología , Animales , Bases de Datos Factuales , Hospitales , Humanos , Fiebre de Lassa/virología , Mamíferos , Prevalencia , RoedoresRESUMEN
Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication.
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Carcinoma Hepatocelular/diagnóstico , Ácidos Nucleicos Libres de Células/genética , Hepatitis B Crónica/diagnóstico , Neoplasias Hepáticas/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Aflatoxina B1/toxicidad , Anciano , Anciano de 80 o más Años , Camerún , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Ácidos Nucleicos Libres de Células/sangre , República Centroafricana , ADN Viral/genética , Femenino , Expresión Génica , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Tasa de Mutación , Proteína p53 Supresora de Tumor/sangre , Carga Viral , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismoRESUMEN
In Gabon, a central African country, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic. In a recent study, conducted in a semi-urban area (Franceville, Gabon), HBV infection was found to be more prevalent among HIV infected individuals. This study aims to investigate the prevalence and genetic diversity of hepatitis B virus infection among HIV infected individuals, predominantly under antiretroviral therapy, living in fully urbanized area: Libreville, capital of Gabon. Serological and molecular tests were performed to detect HBV infection among patients living with HIV/AIDS (PLHA). We used Monolisa HBsAg ULTRA, Anti-HBc Plus and Anti-HBs Plus EIA kits for serological analyses. HBV DNA viral load (HBV DNA VL) was determined by real time PCR and molecular characterization of HBV strains was performed by sequencing and phylogenetic analysis of partial HBV surface and core genes. At all, 70.2% of patients were under antiretroviral therapy. The prevalence of HBsAg was 8.8% (43/487). Detectable HBV DNA was found in 69.7% (30/43) of HBsAg positive patients and in 17.5% (24/137) HBsAg negative patients. HBV DNA VL was significantly higher among patient with CD4 cell counts less than 200 cells/mm3 than those with CD4 cell counts greater than 500 cells/mm3 (p = 0.008). We confirmed the presence of HBV sub-genotypes QS-A3 (40%), and A4 (20%) and HBV-E genotype (40%). The percentage of resistance to Lamivudine was high (40%) and varied according to the M204V/I motif. Occult hepatitis B infection (OBI) was found in patients with isolated HBcAb and among patients who had completed their HBsAg seroconversion. We detected HBV DNA for one patient without any HBV serological marker. This study provides a new landmark for the comprehension of HBV infection in PLHA in urban areas. OBI enhances HBV DNA prevalence and should be investigated in all HBsAg negative individuals.
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ADN Viral/aislamiento & purificación , Infecciones por VIH/complicaciones , Virus de la Hepatitis B/genética , Hepatitis B/complicaciones , Adolescente , Adulto , Recuento de Linfocito CD4 , Femenino , Gabón/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
OBJECTIVES: To determine the seroprevalence of hepatitis E virus (HEV) infection in patients with chronic hepatitis and/or hepatocellular carcinoma (HCC) and to assess its potential consequences for disease progression. METHODS: We conducted a prospective case-control study on patients with HCC hepatitis B or C related and non-HCC patients including patients with CLD and patients without clinical evidence of liver disease. Anti-HEV IgG and IgM were tested by ELISA using commercially available kits. Liver damage was assessed by alanine aminotransferase, aspartate aminotransferase, platelets and prothrombin measurements. RESULTS: We observed a significant anti-HEV IgG carriage in HCC patients compared to non-HCC subjects with CLD (41.8% vs 12.6%; P=9.1 E-6; OR=4.8, 95%CI: 2.3-10.6). HCC patients with HEV infection display more profound alterations of circulating liver enzymes, platelets count and prothrombin time than HCC patients without sero-reactivity to HEV. CONCLUSION: Overall, this study indicates a high prevalence of HEV infection in Cameroonian patients with CLD and HCC. These data suggest either that patients with liver tumors are more susceptible to hepeviral infection or that, in a tropical context, HEV might promote the progression of liver diseases towards tumor.
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Carcinoma Hepatocelular/virología , Virus de la Hepatitis E , Hepatitis E/complicaciones , Adulto , Camerún/epidemiología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Antihepatitis , Hepatitis B/complicaciones , Hepatitis E/epidemiología , Virus de la Hepatitis E/inmunología , Hepatitis Crónica/complicaciones , Humanos , Neoplasias Hepáticas , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.
Asunto(s)
Coinfección , Genotipo , Infecciones por VIH/virología , Virus de la Hepatitis B/genética , Hepatitis B/virología , Mutación , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Gabón/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Seropositividad para VIH , VIH-1/inmunología , Hepatitis B/epidemiología , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de la Hepatitis B/genética , Antígenos de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , Análisis de Secuencia de ADN , Carga ViralRESUMEN
The in vitro antioxidant properties, cytoprotective activity, and ability to induce nuclear translocation of nuclear factor E2-related factor-2 (Nrf-2) of five solvent fractions of the methylene chloride/methanol (1:1 v/v) extract of Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) were evaluated. Five antioxidant endpoints were used in the antioxidant activity investigation. The total phenolic content of the fractions was assessed as to the Folin-Ciocalteu method and the profile of interesting fractions analyzed by high-performance liquid chromatography (HPLC). The cytoprotective activity of fractions was determined by H2O2-induced oxidative stress in HC-04 cells by measuring lactate dehydrogenase (LDH) leakage into culture medium. HC-04 cells were used to investigate the ability to induce nuclear translocation of Nrf2. For both plants, the methylene chloride/methanol (90/10; v/v) fraction (F10), methylene chloride/methanol (75/25; v/v) (F25), and the methanolic fraction (F100) were found to have the highest total polyphenol content and exhibited high antioxidant activity strongly correlated with total polyphenol content. The cytoprotective activity of fraction F25 from both plants was comparable to that of quercetin (3.40 ± 0.05 µg/mL), inhibiting LDH leakage with a low half inhibition concentration (IC50) of 4.05 ± 0.03 and 3.8 ± 0.02 µg/mL for K. grandifoliola and E. africana, respectively. Lastly, fraction F25 of K. grandifoliola significantly (P < 0.05) induced nuclear Nrf2 translocation by sixfold, whereas that from E. africana and quercetin was only twofold. The results indicate for the first time that fraction F25 of the studied plants is more antioxidant and cytoprotective and induces nuclear translocation of Nrf2 in a human hepatocyte cell line.