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Said Ali Al Baqlani Bui Tien Sy Boris A. Ratsch Khalid Al Naamani Salah Al Awaidy Suleiman Al Busaidy Georg Pauli C.-Thomas Bock 《PloS one》2014,9(5)
Background
Hepatitis B virus (HBV) infection is a major global health burden with distinct geographic public health significance. Oman is a country with intermediate HBV carrier prevalence; however, little is known about the incidence of HBV variants in circulation. We investigated the HBV genotype distribution, the occurrence of antiviral resistance, and HBV surface antigen (HBsAg) escape mutations in HBsAg-positive patients in Oman.Methods
Serum samples were collected from 179 chronically HBV-infected patients enrolled in various gastroenterology clinics in Oman. HBV genotypes were determined by sequencing and phylogenetic analysis. Mutations in the HBV polymerase and the HBsAg gene were characterized by mutational analysis.Results
HBV genotypes D (130/170; 76.47%) and A (32/170; 18.28%) are predominant in Oman. The HBV genotypes C and E were less frequent (each 1.18%), while the HBV genotypes B, G, F, and H were not detected. Four patients revealed HBV genotype mixtures (HBV-A/D and D/C). The analyses of vaccine escape mutations yield that 148/170 (87.06%) HBV sequences were wild type. 22/170 (12.94%) HBV sequences showed mutations in the “a” determinant of the HBsAg domain. Two patients showed the described HBV vaccine escape mutation sP120T. 8/146 (5.48%) HBV isolates harbored mutations in the HBV polymerase known to confer resistance against antiviral therapy. Especially the lamivudine resistance mutations rtL180M/rtM204V and rtM204I were detected.Conclusion
This study shows the distribution of HBV genotypes, therapy resistance, and vaccine escape mutations in HBV-infected patients in Oman. Our findings will have a major impact on therapy management and diagnostics of chronic HBV infections in Oman to control HBV infection in this intermediate HBV-endemic country. 相似文献4.
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Huw Price David Dunn Deenan Pillay Firouze Bani-Sadr Theodora de Vries-Sluijs Mamta K. Jain Noriyoshi Kuzushita Stefan Mauss Marina Nú?ez Reto Nüesch Marion Peters Thomas Reiberger Christoph Stephan Lionel Tan Richard Gilson 《PloS one》2013,8(7)
Background
Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains.Methods
A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine.Results
Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare.Interpretation
TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone. 相似文献6.
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Priyanka Banerjee Rajiv Kumar Mondal Madhuparna Nandi Sumantra Ghosh Mousumi Khatun Nabendu Chakraborty Swatilekha Bhattacharya Arindam RoyChoudhury Soma Banerjee Amal Santra Samir Sil Abhijit Chowdhury Pradip Bhaumik Simanti Datta 《PloS one》2014,9(10)
Background/Aims
HBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura.Methods
From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes.Results
HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation.Conclusions
IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia. 相似文献8.
Thomas John Bender Matthew E. Wise Okey Utah Anne C. Moorman Umid Sharapov Jan Drobeniuc Yury Khudyakov Marielle Fricchione Mary Beth White-Comstock Nicola D. Thompson Priti R. Patel 《PloS one》2012,7(12)
Introduction
In January 2010, the Virginia Department of Health received reports of 2 hepatitis B virus (HBV) infections (1 acute, 1 chronic) among residents of a single assisted living facility (ALF). Both infected residents had diabetes and received assisted monitoring of blood glucose (AMBG) at the facility. An investigation was initiated in response.Objective
To determine the extent and mechanism of HBV transmission among ALF residents.Design
Retrospective cohort study.Setting
An ALF that primarily housed residents with neuropsychiatric disorders in 2 adjacent buildings in Virginia.Participants
Residents of the facility as of March 2010.Measurements
HBV serologic testing, relevant medical history, and HBV genome sequences. Risk ratios (RR) and 95% confidence intervals (CIs) were used to identify risk factors for HBV infection.Results
HBV serologic status was determined for 126 (91%) of 139 residents. Among 88 susceptible residents, 14 became acutely infected (attack rate, 16%), and 74 remained uninfected. Acute HBV infection developed among 12 (92%) of 13 residents who received AMBG, compared with 2 (3%) of 75 residents who did not (RR = 35; 95% CI, 8.7, 137). Identified infection control breaches during AMBG included shared use of fingerstick devices for multiple residents. HBV genome sequencing demonstrated 2 building-specific phylogenetic infection clusters, each having 99.8–100% sequence identity.Limitations
Transfer of residents out of the facility prior to our investigation might have contributed to an underestimate of cases. Resident interviews provided insufficient information to fully assess behavioral risk factors for HBV infection.Conclusions
Failure to adhere to safe practices during AMBG resulted in a large HBV outbreak. Protection of a growing and vulnerable ALF population requires improved training of staff and routine facility licensing inspections that scrutinize infection control practices. 相似文献9.
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Summer L. Day Katherine Odem-Davis Kishorchandra N. Mandaliya Keith R. Jerome Linda Cook Linnet N. Masese John Scott H. Nina Kim Susan M. Graham R. Scott McClelland 《PloS one》2013,8(3)
Background
Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART.Methods
In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression.Results
In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4–4.5), 11 (6.9%; 95% CI 3.1–10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1–5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression.Conclusion
The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population. 相似文献11.
Vici Varghese Elijah Wang Farbod Babrzadeh Michael H. Bachmann Rajin Shahriar Tommy Liu Svetlana Jean M. Mappala Baback Gharizadeh W. Jeffrey Fessel David Katzenstein Seble Kassaye Robert W. Shafer 《PloS one》2010,5(6)
Background
The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses.Methods and Findings
We performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR-induced K65R mutation in subtype C viruses.Conclusions
This study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo. 相似文献12.
Background
MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response and tumorigenesis. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7.Methods
We performed a case-control study including 1300 HBV-positive hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the association between rs999885 and the risk of HBV persistent infection and HCC. We also investigated the genotype-expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of HCC and adjacent non-tumor liver tissues.Results
Compared with the HBV natural clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of 0.79 [95% confidence intervals (CIs) = 0.67–0.93]. However, the AG/GG genotypes were significantly associated with an increased HCC risk in HBV persistent carriers (adjusted OR = 1.25, 95% CIs = 1.06–1.47). Expression analysis revealed that the expression level of miR-106b-25 cluster was significantly higher in AG/GG carriers than those in AA carriers in non-tumor liver tissues.Conclusions
These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. 相似文献13.
Craig W. Hendrix Beatrice A. Chen Vijayanand Guddera Craig Hoesley Jessica Justman Clemensia Nakabiito Robert Salata Lydia Soto-Torres Karen Patterson Alexandra M. Minnis Sharavi Gandham Kailazarid Gomez Barbra A. Richardson Namandje N. Bumpus 《PloS one》2013,8(1)
Background
Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.Objective
MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.Methods and Findings
We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03).Conclusions
Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir’s antiviral effect substantially influence PrEP efficacy.Trial Registration
ClinicalTrials.gov NCT00592124相似文献14.
Nawarat Posuwan Sunchai Payungporn Pisit Tangkijvanich Shintaro Ogawa Shuko Murakami Sayuki Iijima Kentaro Matsuura Noboru Shinkai Tsunamasa Watanabe Yong Poovorawan Yasuhito Tanaka 《PloS one》2014,9(1)
Background
Previous studies showed that single nucleotide polymorphisms (SNPs) in the HLA-DP, TCF19 and EHMT2 genes may affect the chronic hepatitis B (CHB). To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs.Methods
The participants for this study were defined into 4 groups; HCC (n = 230), CHB (n = 219), resolved HBV infection (n = 113) and HBV uninfected subjects (n = 123). The HLA-DP SNPs (rs3077, rs9277378 and rs3128917), TCF19 SNP (rs1419881) and EHMT2 SNP (rs652888) were genotyped.Results
Due to similar distribution of genotype frequencies in HCC and CHB, we combined these two groups (HBV carriers). The genotype distribution in HBV carriers relative to those who resolved HBV showed that rs3077 and rs9277378 were significantly associated with protective effects against CHB in minor dominant model (OR = 0.45, p<0.001 and OR = 0.47, p<0.001). The other SNPs rs3128917, rs1419881 and rs652888 were not associated with HBV carriers.Conclusions
Genetic variations of rs3077 and rs9277378, but not rs3128917, rs1419881 and rs652888, were significantly associated with HBV carriers relative to resolved HBV in Thai population. 相似文献15.
Anand Patel Jacquelyn Dunmore-Griffith Stephen Lutz Peter A.S. Johnstone 《Reports of Practical Oncology and Radiotherapy》2014,19(3):191-194
Aim
We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life.Background
Few objective data exist for radiation therapy (RT) delivery at end of life (EOL).Materials and methods
Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life.Results
A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2–30 days).Conclusions
Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric. 相似文献16.
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Objective
To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China.Methods
2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections.Results
The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection.Conclusions
HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors. 相似文献19.
Feng Xie Long Yan Jiongjiong Lu Tao Zheng Changying Shi Jun Ying Rongxi Shen Jiamei Yang 《PloS one》2013,8(1)
Purpose
The effectiveness of nucleoside analogue on patients with chronic hepatitis B-associated liver failure is still controversial. To address this issue, we did a review of the literatures and analyzed the data with emphasis on the survival and reduction in serum HBV DNA level.Methods
We searched 11 randomized controlled trials that included 654 patients with chronic hepatitis B-associated liver failure. 340 patients adopted nucleoside analogue, such as lamivudine (LAM), entecavir (ETV), telbivudine (LdT), or tenofovir disoproxil fumarate (TDF), and the remaining 314 patients adopted no nucleoside analogue or placebo. A meta-analysis was carried out to examine the survival, HBV e antigen serologic conversion, and reduction in serum HBV DNA level. The pooled odds ratio (OR) was used to reflect the treatment effects.Results
The overall analysis revealed nucleoside analogue significantly improved 1-month(OR = 2.10; 95% CI, [1.29, 3.41]; p = 0.003), 3-month (OR = 2.15; 95% CI, [1.26, 3.65]; p = 0.005), 12-month survival (OR = 4.62; 95% CI, [1.96, 10.89]; p = 0.0005). Comparison of 3-month HBV DNA showed significant reduction for adoptive nucleoside analogue patients (OR = 54.47; 95% CI, [16.37, 201.74]; p<0.00001). Comparison of 3-month HBV e antigen serologic conversion showed a highly significant improvement of HBV e antigen lost for patients received adoptive antiviral therapy (OR = 6.57; 95% CI, [1.64, 26.31]; p = 0.008).Conclusions
The benefits of nucleoside analogue on patients with chronic hepatitis B-associated liver failure is significant for improving patient survival, HBV e antigen serologic conversion, and rapid reduction of HBV DNA levels. 相似文献20.
S Jasuja ND Thompson PJ Peters YE Khudyakov MT Patel P Linchangco HT Thai WM Switzer A Shankar W Heneine DJ Hu AC Moorman SI Gerber 《PloS one》2012,7(8):e43252