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Hepatitis B [keywords]
- Discrepant Hepatitis B Surface Antigen Results in Pregnant Women Screened to Identify Hepatitis B Virus Infection. [JOURNAL ARTICLE]
- J Pediatr 2014 Jul 22.
To resolve discrepant hepatitis B surface antigen (HBsAg) results for pregnant women screened for hepatitis B virus (HBV) infection.A case was defined as discrepant HBsAg (reactive followed by non-reactive) result during the same pregnancy. The Centers for Disease Control and Prevention examined a convenience sample of cases passively reported by US Perinatal Hepatitis B Prevention Programs. Using a standard form, available results were obtained for hepatitis B tests and vaccination histories. Results were independently reviewed by 3 viral hepatitis experts and a clinical virologist to resolve discrepancies. The initial HBsAg result was classified as probable true positive, probable false positive, or unresolved.From April 2009-December 2011, 142 (75.9%) of 187 reported discrepant cases met the case definition. Of the 142 initial reactive HBsAg results, 113 (79.5%) were laboratory-confirmed, and 89 (62.7%) were resolved. Among these 89 cases, the initial test was a probable true positive in 14 (15.7%), and a false positive in 75 (84.3%). Total antibody to hepatitis B core antigen was positive for 11 (78.6%) of the true positive cases and negative for 67 (89.3%) of the false positive cases. True positives included 2 cases of resolving acute HBV infection and one case recently given hepatitis B vaccination.In this retrospective analysis of discrepant HBsAg-reactive screening results from pregnant women, the majority were false positives, but true positives occurred. Testing for total hepatitis B core antigen, an indicator of past or current HBV infection, was useful for resolving discrepancies.
- Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication. [JOURNAL ARTICLE]
- Gut 2014 Jul 25.
Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated.To assess whether human HSCs are susceptible to HCV infection.We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs.In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication.Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
- Allaitement maternel : les bénéfices pour la santé de l'enfant et de sa mère. [JOURNAL ARTICLE]
- Arch Pediatr 2013 Nov.:S29-S48.
The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mother's milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.
- Concurrent Use of Comedications Reduces Adherence to Antiretroviral Therapy Among HIV-Infected Patients. [Journal Article]
- J Manag Care Pharm 2014 Aug; 20(8):844-50.
The use of highly active antiretroviral therapy has significantly reduced morbidity and mortality, thus increasing life expectancy of human immunodeficiency virus (HIV)-infected individuals, transforming HIV into a chronic disease. Accordingly, there has been an increase in the number of comorbidities concomitantly present in these individuals and also an increased use of comedications, which may negatively impact antiretroviral therapy adherence. These factors can affect adherence to antiretroviral therapy. The role of the HIV clinical pharmacist is essential to achieve therapeutic objectives and enhance adherence.To determine the influence of the comorbidities and comedications on antiretroviral therapy adherence among HIV-infected patients receiving services from a clinical pharmacist.We conducted a prospective observational study that included HIV-infected outpatients who attended the pharmaceutical care office of a hospital pharmacy service, which initiated antiretroviral treatment between January 2002, and December 2011. The variables analyzed in the study were demographics (sex and age), HIV transmission mode, and the following variables at the time of comedication collection: hepatitis C virus or hepatitis B virus coinfection, HIV plasma viral load (copies/mL) and CD4+ T-cell count (cells/µL), Centers for Disease Control and Prevention HIV classification, number of hospital admissions and emergency room visits, and antiretroviral therapy-related features (type at baseline, treatment-naïve status, and number of changes since starting antiretroviral therapy). For follow-up at 12 months, antiretroviral therapy adherence was measured through pharmacy dispensing records and the Morisky Medication Adherence Scale (MMAS). Patients were considered adherent if antiretroviral therapy adherence through dispensing records was greater than 90%, and the MMAS score was 4. Other variables were number of comorbidities and number of comedications for other chronic diseases (non-HIV drugs). According to the number of comorbidities, patients were categorized as having multiple chronic conditions (polypathology) if they had 2 or more chronic diseases. Polypharmacy was defined specifically as the use of 5 or more prescription medications in a medication regimen. In addition, a complexity therapeutic index of antiretroviral therapy was calculated for each patient. We determined the risk of drug-related problems using the tool Predictor Index. To identify independent predictors of adherence to antiretroviral therapy, we performed a univariate logistic regression. Afterward, those variables that showed statistical significance in the univariate analysis and those with P less than 0.25 were included in a multivariate model. The sample size was estimated by the Freeman equation.We included 594 patients in the study (80.1% men, median age 47 years). In the univariate analysis, the variables that showed statistically significant relationships with antiretroviral therapy adherence were HIV transmission mode, detectable viral load, CD4+ T-cell count, AIDS-defining condition, hospital admission, antiretroviral therapy-naïve treatment, type of antiretroviral therapy, high risk of drug-related problems, polypathology, and polypharmacy. Multivariate analysis showed that independent predictors of nonadherence to antiretroviral therapy were HIV transmission by intravenous drug use (OR = 0.56, 95% CI = 0.35-0.90), previous treatment with antiretroviral therapy (OR = 0.09, CI = 0.04-0.24), nontreatment changes (OR = 0.12, CI = 0.05-0.31), high risk of drug-related problems (OR = 0.38, CI = 0.23-0.63), and polypharmacy (OR = 0.36, CI = 0.21-0.61). The value of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.378).Recently, the number of HIV-infected patients with polypharmacy has been higher, increasing the risk of nonadherence. Furthermore, previous treatment with antiretroviral therapy, HIV transmission by intravenous drug use, and high risk of drug-related problems are also associated with lower adherence.
- Relationship between RUNX3 methylation and hepatocellular carcinoma in Asian populations: a systematic review. [JOURNAL ARTICLE]
- Genet Mol Res 2014; 13(3):5182-5189.
Runt-related transcription factor 3 (RUNX3) is a potential tumor suppressor that is frequently hypermethylated in hepatocellular carcinoma (HCC). The present meta-analysis of case-control studies was carried out to determine whether RUNX3 hypermethylation is associated with HCC. The PubMed, Embase, and Chinese National Knowledge Infrastructure databases were searched for all relevant studies published between May 2000 and May 2012. A total of 11 studies were identified, and 8 studies involving 491 patients with HCC and 409 patients without tumors were found to satisfy the inclusion criteria for the meta-analysis. All tissue samples were from Asian populations. There was significant heterogeneity between the studies. Over the entire sample, the odds ratio (OR) of RUNX3 promoter methylation was 18.5 [95% confidence interval (CI), 11.6-29.6] for HCC tissues relative to control tissues. The ORs of RUNX3 methylation were 16.6 (95%CI = 6.5-42.4) for tumor tissues relative to tumor-adjacent tissues in patients with HCC, 67.3 (95%CI = 13.0-348.5) for tumor tissues from patients with HCC relative to liver tissues from patients with non-neoplastic liver diseases, and 3.26 (95%CI = 1.54-6.90) for tissues from patients with hepatitis C virus (HCV)- related HCC relative to liver tissues from patients with HCC unrelated to HCV. There was no association between RUNX3 methylation and age, gender, pathological stage, or hepatitis B virus infection in HCC tissues. Methylation of the RUNX3 promoter strongly correlated with HCC in Asian populations, especially in individuals with HCV-related HCC, and may be a useful marker for HCC diagnosis in these populations.
- Association of miR-149C>T and miR-499A>G polymorphisms with the risk of hepatocellular carcinoma in the Chinese population. [Journal Article]
- Genet Mol Res 2014; 13(3):5048-54.
We investigate the potential association of miR-149C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC). A matched case-control study of 152 cases and 304 controls were conducted. The miR-149C>T and miR-499A>G genotypes were analyzed using duplex polymerase chain reaction with restricted fragment length polymorphism. HCC patients were more likely to be smokers and drinkers, have hepatitis B and C virus infections, and a family history of cancer. The miR-149 CC genotype was associated with a reduced risk of HCC, while the miR-499 GG genotype was associated with an increased risk of HCC. However, we did not find that the miR-149 CC and miR-499 GG genotypes were associated with risk of HCC, and no interaction was found between miR-149C>T and miR-499A>G polymorphisms and hepatitis B virus infection. In conclusion, the miRNA-149C>T and miR-499A>G polymorphisms were found to play an important role for HCC risk in China. This finding could be useful in identifying people at high risk for the disease for early intervention.
- Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir. [Journal Article]
- Drug Des Devel Ther 2014.:869-73.
Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out.
- Low Treatment Rates in Patients Meeting Guideline Criteria in Diverse Practice Settings. [JOURNAL ARTICLE]
- Dig Dis Sci 2014 Jul 25.
Data on usage of antiviral therapy and application of chronic hepatitis B (CHB) management guidelines in different settings are limited. Our goal is to evaluate the proportion of treatment-eligible patients by 6-month follow-up and treatment rate among eligible patients by 12-month follow-up in diverse settings.In this retrospective cohort study, 1,976 treatment-naïve CHB patients were categorized as primary care physician (PCP) group if seen by community PCP (n = 329), gastroenterology (GI) group if seen by community gastroenterologists (n = 1,268), and hepatology group if seen by university hepatologists (n = 379). Treatment eligibility was based on the US Panel 2008 and American Association for the Study of Liver Diseases (AASLD) 2009 guidelines.All groups had similar age, gender, and ethnic distribution. GI and hepatology groups had similar treatment eligibility rates by US Panel (53-54 %) and AASLD guidelines (24-25 %). However, treatment rate was significantly higher in hepatology compared to GI group by the US Panel guideline (59 vs. 45 %, P = 0.001). PCP group had the lowest eligibility and treatment rates by both guidelines. Common reasons for non-treatment were perceived "normal" alanine aminotransferase, desire for further observation, and patient refusal. Male gender, age >50, and subspecialty care predicted treatment initiation in treatment-eligible patients.Less than half of treatment-eligible patients at primary care clinics received treatment. Community gastroenterology and university liver clinics treated about one-half to two-thirds of eligible patients. Patient and provider education should highlight treatment benefits and the new alanine aminotransferase upper limit of normal.
- Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG-interferon. [JOURNAL ARTICLE]
- J Viral Hepat 2014 Jul 24.
In HBV-infected patients, the vitamin D deficiency has been related to chronic liver diseases, progression of hepatic fibrosis and poor response to the treatment. The CYP27B1 gene, which encodes the 1-α-hidroxylase and involved in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1 diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative treated for 48 weeks with PEG-IFN α-2a. We examined the role of rs4646536 CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our results showed that the TT genotype of CYP27B1+2838 was significantly prevalent in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P < 0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%) vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the TT genotype resulted to be a good positive predictor of sustained virological response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be useful as pretreatment factor to selection of patients with higher probability of response to therapy.
- Risk factors for bloodborne viral hepatitis in healthcare workers of Pakistan: a population based case-control study. [Journal Article]
- BMJ Open 2014; 4(7):e004767.
A high prevalence of viral hepatitis B and C was found among healthcare workers during a province-wide screening in Sindh Province, Pakistan. A follow-up study was undertaken to identify risk factors for this high prevalence in healthcare workers.Population based case-control design.Public sector healthcare facilities in a rural district of Pakistan.Healthcare workers who were screened for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibodies. 178 healthcare workers employed at the public sector clinics and hospitals of the district were approached, of which 14 refused to participate. Cases had detectable serum antibodies against HCV and the presence of HBsAg. Healthcare workers non-reactive to HCV antibodies and with no HBsAg were controls. These were matched in a ratio of 1:1.Detectable serum HBsAg and HCV antibody titer were taken as outcome. OR for various exposures was calculated; those with p<0.25 were entered in a multivariate logistic regression model to find out significant predictors.Needle stick injury (OR=6; CI95 1.4 to 23), recapping the needle (OR=5.7; CI95 1.1 to 28), wound care at accident and emergency of a hospital (OR=5.5; CI95 1 to 28), female gender (OR=3.4; CI95 1 to 12) and more than 10 years of formal education (OR=0.25; CI95 0.07 to 0.8) were associated with hepatitis C. Hepatitis B was found to be associated with trying to bend or break a needle after use (OR=4.9; CI95 1 to 24).Healthcare workers in Pakistan are at additional risk of exposure to bloodborne pathogens. Bi-dimensional risk factors present at individual and broader health systems levels are responsible. Occupational safety, health trainings and redesigning of the curriculum for allied health professionals are required.