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Hepatitis B [keywords]
- Analysis of ultra-deep pyrosequencing and cloning based sequencing of the basic core promoter/precore/core region of hepatitis B virus using newly developed bioinformatics tools. [Journal Article]
- PLoS One 2014; 9(4):e95377.
The aims of this study were to develop bioinformatics tools to explore ultra-deep pyrosequencing (UDPS) data, to test these tools, and to use them to determine the optimum error threshold, and to compare results from UDPS and cloning based sequencing (CBS).Four serum samples, infected with either genotype D or E, from HBeAg-positive and HBeAg-negative patients were randomly selected. UDPS and CBS were used to sequence the basic core promoter/precore region of HBV. Two online bioinformatics tools, the "Deep Threshold Tool" and the "Rosetta Tool" (http://hvdr.bioinf.wits.ac.za/tools/), were built to test and analyze the generated data.A total of 10952 reads were generated by UDPS on the 454 GS Junior platform. In the four samples, substitutions, detected at 0.5% threshold or above, were identified at 39 unique positions, 25 of which were non-synonymous mutations. Sample #2 (HBeAg-negative, genotype D) had substitutions in 26 positions, followed by sample #1 (HBeAg-negative, genotype E) in 12 positions, sample #3 (HBeAg-positive, genotype D) in 7 positions and sample #4 (HBeAg-positive, genotype E) in only four positions. The ratio of nucleotide substitutions between isolates from HBeAg-negative and HBeAg-positive patients was 3.5∶1. Compared to genotype E isolates, genotype D isolates showed greater variation in the X, basic core promoter/precore and core regions. Only 18 of the 39 positions identified by UDPS were detected by CBS, which detected 14 of the 25 non-synonymous mutations detected by UDPS.UDPS data should be approached with caution. Appropriate curation of read data is required prior to analysis, in order to clean the data and eliminate artefacts. CBS detected fewer than 50% of the substitutions detected by UDPS. Furthermore it is important that the appropriate consensus (reference) sequence is used in order to identify variants correctly.
- [Evaluation on the efficacy of prevention programs and relevant factors targeting mother-to-infant transmission on hepatitis B virus in Yunnan province]. [English Abstract, Journal Article]
- Zhonghua Liu Xing Bing Xue Za Zhi 2014 Feb; 35(2):114-6.
To explore the efficacy of prevention programs and relevant factors targeting mother-to-infant transmission of HBV in Yunnan province.In Yunnan province, we selected HBsAg positive pregnant women that delivered in hospital from January 1st through June 30th, 2011. Newborns of these pregnant women were under PMTCT (prevention of mother to child treatment) program and followed. Every infant was drawn 2 ml venous blood and questionnaire survey was carried out when the baby was 7-12 month-old and completed the vaccination processes. Serum samples of them were then collected and detected on the 5 serological indicators of HBV.were analyzed statistically.There were 2 765 infants in the study program. The success rate of PMTCT was 95.88% . Rates of coverage on both timely-birth dose and 3 doses of HepB were 97.03% and 92.30% respectively. The overall vaccinated rate and timely-birth vaccinated rate on hepatitis B immunoglobulin (HBIG) were 68.97% and 94.49% respectively. The success rate of PMTCT was 97.16% after administration of passive-active immune-prophylaxis (HepB and HBIG), compared to the rate as 93.01% when vaccinated with HepB only. Significant differences were seen in the successful rates of PMTCT between combined and non-combined immunization. Either the combined or non-combined immunization, there were significant differences seen in the success rates of PMTCT regardless the positivity status of HBsAg or HBeAg, among the infected mothers.The efficacy of passive-active immune-prophylaxis program seemed to be better than the one without combined immunization. It was vitally important for the infants whose mothers' HBsAg and HBeAg status were positive, to receive regular and timely combined immunization. In order to promote the PMTCT in Yunnan province, vaccinated rate on HBIG should be further improved.
- On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy. [JOURNAL ARTICLE]
- Antivir Ther 2014 Apr 16.
Serum HBV RNA is detectable during nucleos(t)ide analogue therapy as the consequence of unaffected RNA replicative intermediates or interrupted reverse transcription. We studied the predictive value of serum HBV RNA for initial virologic response during nucleoside analogue therapy.Serum HBV RNA was quantified before and at 12 and 24 weeks of lamivudine or entecavir therapy. Serum HBV DNA was measured every 4 to 12 weeks during treatment to define initial virologic response.Serum HBV RNA was detectable in 21 of 52 (40%) consecutive patients with the mean of 5.2 log copies/mL (M/F 35/17; mean age of 60 years with the range from 31 to 82; 44% HBeAg-positive; 26 with lamivudine and 26 with entecavir) before treatment. Serum HBV RNA level at week 12 in patients with interval from detectable to undetectable serum HBV DNA level < 16 weeks was significantly lower than those with interval ≥ 16 weeks (3.8 ± 3.8 versus 6.6 ± 3.5 log copies/ml, p=0.013). After adjustment for serum HBV DNA level at week 12, serum qHBsAg level at week 12, and pre-treatment ALT level, low serum HBV RNA level at week 12 predicted a shorter interval to become undetectable serum HBV DNA level (adjusted hazard ratio=0.908, 95% CI=0.829-0.993, p=0.035).Low serum HBV RNA level at week 12 of nucleoside analogue therapy independently predicts initial virologic response in treated chronic hepatitis B patients. Serum HBV RNA level may thus be useful to optimize the treatment of chronic hepatitis B.
- Peginterferon alfa in the treatment of chronic Hepatitis B. [JOURNAL ARTICLE]
- Expert Opin Biol Ther 2014 Apr 16.
Introduction: Hepatitis B virus (HBV) infection is a global health problem. Peginterferon α (PEG-IFN), which includes PEG-IFN α-2a (Pegasys) and PEG-IFN α-2b (Peg-Intron), can be used to treat patients with chronic hepatitis B (CHB) infection. A finite duration of PEG-IFN therapy may lead to long-term viral suppression. Clinically, it is important to identify super-responders and null-responders to PEG-IFN due to its substantial side effects. Areas covered: From the literature review, it is known that PEG-IFN is more effective for hepatitis B e antigen (HBeAg)-positive patients who have high pre-treatment alanine aminotransferase level, lower HBV DNA level and genotype A (vs genotype D), as well as those with more favourable viral predictors, such as precore stop codon or basal core promoter mutants infections in Asian patients and wild-type virus in Caucasian patients. For HBeAg-positive patients and HBeAg-negative patients with genotype D infection, PEG-IFN therapy could be terminated early at week 12 or 24 in primary non-responders defined by the Hepatitis B surface antigen stopping rules. With regard to host factors, single nucleotide polymorphisms of IL28B do not seem to affect the treatment outcomes in Asian patients, but its role in Caucasian patients remains disputed. Expert opinion: Most of the known predictors need validation by large prospective trials. In addition, we need to identify more baseline predictors for super-responders in order to achieve personalised PEG-IFN treatment for CHB.
- Comparison of seven hepatitis B virus (HBV) nucleic acid testing assays in selected samples with discrepant HBV marker results from United States blood donors. [JOURNAL ARTICLE]
- Transfusion 2014 Apr 17.
Sensitive triplex nucleic acid tests (NATs) are implemented for blood donation screening worldwide. Assays have variable ability to detect low-level hepatitis B virus (HBV) DNA. At borderline DNA detection levels, where Poisson distribution impacts results, distinguishing true-positive from false-positive results is challenging. Algorithms are needed to confirm such low-level HBV DNA-positive samples.A total of 135 blood donor samples reactive by one or more HBV markers that provided discrepant results were tested undiluted with four commercial NATs: Ultrio, Ultrio Plus, MPX, and a quantitative assay (SuperQuant). To further explore discrepancies, three additional in-house NATs including real-time polymerase chain reaction (PCR) and nested PCR and sequencing were performed.The numbers reactive of these 135 "difficult" samples by four commercial NATs were as follows: 39 of 107 (36%) with SuperQuant, 40 (30%) with Ultrio, 100 (74%) with Ultrio Plus, and 102 (76%) with MPX. Of the seven NATs, 109 (81%) samples were reactive by at least two assays and thus considered confirmed positive of which 67 (50%) generated a sequence. Ultrio Plus and MPX performed similarly as above (80%-85% detected of 109 and 81%-90% of 67, respectively). Older (median, 49 years), HBV core antibody-reactive donors carried predominantly Genotype A (58%) with high-frequency amino acid substitutions in the major hydrophilic region of the S-protein. Younger (median, 24 years) hepatitis B surface antigen-positive donors carried wild-type strains predominantly Genotype B (32%) and E (24%), the latter in an apparent cluster.Highly sensitive NATs require new confirmatory algorithms as presented optimally using different genomic regions or sequence generation. The introduction of immigration-related HBV genotypes may impact HBV epidemiology in the United States.
- [Quantitative determination of HBsAg in blood sera and hepatitis B virus covalently closed circular DNA in liver tissue as markers of chronic viral hepatitis B activity]. [English Abstract, Journal Article]
- Zh Mikrobiol Epidemiol Immunobiol 2014 Jan-Feb; (1):55-61.
Quantitative evaluation of HBV covalently closed circular DNA (cccDNA) content in liver tissue of patients with moderately active CHBV course compared with inactive HBsAg carriers as well as establishment of a possible link between HBV cccDNA in liver cells and HBsAg level in blood sera in these groups of patients.Patients (n = 34) with CHBV diagnosis were examined for levels ofALT, HBsAg (qualitatively and quantitatively), anti-HBcor IgG, anti-HBe IgG, anti-HCV IgG+IgM, anti-HDV IgG+IgM, HBV DNA in qualitative and quantitative variant. Liver biopsy was carried out in all the patients. HBV DNA was determined in liver tissue by Pollicino T. et al. (2004).Based on HBV DNA PCR, the patients were allocated to a group of inactive HBsAg carriers (n = 16) and CHBV (n = 18) of moderate activity. Viral load in CHBV patients had a mean of 540 +/- 230 IU/ml. ALT level in carriers was comparatively lower than in patients with CHBV. HBsAg level in blood of inactive carriers was significantly lower, 940 +/- 259 IU/ml against 2559 +/- 982 IU/ml in patients with CHBV (p < 0.05). The quantity of cccDNA per 1 cell in inactive HBsAg carriers--0.15 +/- 0.14, and in patients group of CHBV with moderate activity--1.71 +/- 1.32 (p = 0.034).The method of quantitative determination of HBV cccDNA in liver tissue of patients was worked out. Differences in quantitative content of HBsAg in blood sera of inactive carriers and CHBV patients with moderate activity reflect changes in the extent of hepatocyte infection by HBV.
- [Actual problems of vaccine prophylaxis in the Russian Federation]. [English Abstract, Journal Article]
- Zh Mikrobiol Epidemiol Immunobiol 2014 Jan-Feb; (1):9-19.
The WHO within the framework of extended immunization program assumes a significant increase of the number of vaccine controlled infections by 2020 - 2025 to 27 - 37 including protection from diseases of parasitic etiology. Russia contributes to the international efforts of the WHO to control infections with vaccine prophylaxis. The national calendar of prophylaxis vaccinations currently provides vaccination against 11 infections--tuberculosis, hepatitis B, poliomyelitis, pertussis, diphtheria, tetanus, measles, rubella, epidemic parotitis, influenza, haemophilus type B infection. Significant progress in reduction of infectious morbidity controlled by means of specific prophylaxis has been made in the country.
- Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma. [REVIEW]
- Biomed Res Int 2014.:106247.
Hepatocellular carcinoma (HCC) incidence is increasing worldwide in recent years. Most HCC cases develop in the presence of advanced chronic liver disease related to chronic hepatitis C virus (HCV) infection, chronic hepatitis B (HBV) infection, and alcohol abuse. Approximately 15-50% of HCC cases are classified as idiopathic, suggesting that other risk factors are responsible for its rising incidence. Recent studies suggest that nonalcoholic fatty liver disease (NAFLD) can be associated with these "idiopathic" cases. NAFLD progresses slowly and can develop into liver cirrhosis, liver failure, and HCC. In the last few years, NAFLD has received more attention because of its high prevalence worldwide.
- [Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia]. [English Abstract, Journal Article]
- Medicina (B Aires) 2014; 74(2):130-2.
Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.
- Predictors of optional immunization uptake in an urban south Indian population. [JOURNAL ARTICLE]
- Vaccine 2014 Apr 12.
In Tamil Nadu, India, bacille Calmette-Guérin, diphtheria-tetanus-pertussis, oral poliomyelitis, hepatitis B, and measles vaccines are part of the routine immunization schedule and are available free from government health centers. All other vaccines are optional and available in the private sector at a cost to families. This study assesses immunization rates of routine and optional vaccines and examines parental attitudes toward vaccines in Pallavapuram, Tamil Nadu.The cluster sampling method was used to estimate immunization coverage. Seven children 18 to 36 months old were selected from 30 clusters for a total sample of 210 children. Demographics and vaccination data were collected from interviews and immunization records. Predictors of vaccination status were identified with logistic regression models. In addition, 21 parents participated in semi-structured interviews regarding their attitudes toward vaccination. Interviews were analyzed qualitatively for themes.Eighty one percent of children were fully immunized with routine vaccines. However, only 21% received all "major" optional vaccines, defined as 3 doses of Haemophilus influenzae type b vaccine, one dose of measles, mumps, rubella vaccine, and one dose of varicella zoster virus vaccine. Birth in a private hospital (OR 5.6, 95% CI 1.3 to 22.9, P<0.01), higher income (P=0.03), and maternal completion of high school (OR 6.4, 95% CI 1.5 to 27.6, P<0.01) were significant predictors of receiving all major optional vaccines. Elucidated themes from interviews included (1) strong parental support for immunizations, (2) low concern for side effects, and (3) low uptake of optional vaccines due to high cost and lack of awareness.Coverage of optional vaccines is low despite positive attitudes toward immunizations. Efforts to reduce cost and increase awareness of these vaccines particularly among low-income families or to include these vaccines in the routine schedule may increase uptake and reduce morbidity and mortality from vaccine-preventable diseases.