Alterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this ...study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV.
Adult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy.
Among the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107-513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107-208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation.
Spontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.
Hepatitis C virus (HCV) exploits an extensive network of host proteins to maintain chronic infection. Using RNA-Seq technology, we identified 30 host genes that were differentially expressed in cell ...culture grown HCV (HCVcc)-infected cells. Of these candidate genes, we selected solute carrier family 3 member 2 (SLC3A2) for further investigation. SLC3A2, also known as CD98hc, is a member of the solute carrier family and encodes a subunit of heterodimeric amino acid transporter. SLC3A2 and LAT1 constitute a heterodimeric transmembrane protein complex that catalyzes amino acid transport. In this study, we showed that HCV upregulated both mRNA and protein expression levels of SLC3A2 and this upregulation occurred through NS3/4A-mediated oxidative stress. HCV also elevated SLC3A2/LAT1 complex level and thus mammalian target of rapamycin complex 1 (mTORC1) signaling was activated. We further showed that L-leucine transport level was significantly increased in Jc1-infected cells as compared with mock-infected cells. Using RNA interference technology, we demonstrated that SLC3A2 was specifically required for the entry step but not for other stages of the HCV life cycle. These data suggest that SLC3A2 plays an important role in regulating HCV entry. Collectively, HCV exploits SLC3A2 for viral propagation and upregulation of SLC3A2 may contribute to HCV-mediated pathogenesis.
Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion ...protein (PrPC) into the pathological prion protein (PrPSc). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway. The subsequent intensive CWD surveillance launched in cervids resulted in the detection of CWD in moose (Alces alces), with 11 cases in Norway, 3 in Finland and 4 in Sweden. These moose cases differ considerably from CWD cases in North American and reindeer in Norway, as PrPSc was detectable in the brain but not in lymphoid tissues. These facts suggest the occurrence of a new type of CWD. Here, we show some immunohistochemical features that are clearly different from CWD cases in North American and Norwegian reindeer. Further, the different types of PrPSc deposits found among moose demonstrate strong variations between the cases, supporting the postulation that these cases could carry multiple strains of CWD.
Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed.
To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6.
...Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766).
48 U.S. sites.
377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks.
Sustained virologic response at 12 weeks (SVR12).
In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide.
The study was open-label, no inferential statistics were planned, and sample sizes were small.
Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6.
Gilead Sciences.
Hepatitis B in the Female Population Cohen, Erica; Tran, Tram T
Gastroenterology clinics of North America,
06/2016, Letnik:
45, Številka:
2
Journal Article
Recenzirano
Chronic hepatitis B infection in the female population has implications not just for the individual but for her children as well. This article discusses the natural history of hepatitis B and how it ...plays an important role in hepatitis B virus (HBV) transmission, the current strategies and new strategies to control HBV and reduce transmission, and the updated guidelines for the management of HBV.
Background
Studies suggest that gender differences in academic medicine exist. Men frequently have better measures of performance such as number of publications, number of citations, remuneration, ...and funding.
Aims
To evaluate whether a gender disparity in authorship exists.
Methods
We recorded the gender of first and senior authors of original papers, editorials/reviews from liver-related manuscripts in
Gastroenterology
,
Hepatology
,
Transplantation
,
American Journal of Gastroenterology
, and
Liver Transplantation
from January 2014 to 2016.
Results
Of 2424 articles reviewed, we excluded 232 (10%) due to inability to determine gender. Among papers analyzed, 72.0% were original and 28.1% reviews/editorials with 65.1% of first authors being male and 34.9% female. Only 20.3% of papers with multiple authors had a female senior author. The proportion of male first and senior authorship between original papers and reviews/editorials was comparable. 72% of original papers had a male as first or senior author, but only 28% females. 71% of review/editorial papers had a male as first or senior author, but only 29% females. When the senior author of an original paper was female, 47.1% of first authors were male and 52.9% female. When the senior author was male, 67.1% of first authors were male and 32.9% female (
p
< 0.00001).
Conclusions
A significant gender difference exists in Hepatology publications. Female authorship mirrors the percentage of female AASLD membership; however, female senior authorship remains disproportionate. In general, funding for male authors is greater. Fewer women are first authors when the senior author is male, highlighting the importance of female mentorship in Hepatology.
Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors ...including hepatitis B e antigen (HBeAg) positivity and viral load.
To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials.
Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18-69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive.
Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load.
Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic infection with hepatitis C virus (HCV) is common, but underdiagnosed and undertreated worldwide. The most important treatment outcome in HCV is sustained virological response (SVR), due to ...its impact on reducing the risks of liver-related mortality, hepatocellular carcinoma, and hepatic decompensation. The degree of baseline liver disease, IL28B genotype, and HCV genotype are important determinants of response to treatment, and SVR rates less than 50% can be expected for persons with genotype 1 receiving standard peginterferon with ribavirin. The rates are even lower when cirrhosis is present. There is little evidence supporting improved outcomes with peginterferon and ribavirin retreatment, and escalation of ribavirin dosage leads to an increased risk of adverse events. Introduction of the protease inhibitors, boceprevir and telaprevir, has resulted in SVR rates between 67% and 79% when used as part of a triple therapy regimen, which has become the standard of care for those with genotype 1 HCV. More work is needed to develop strategies to further improve treatment outcomes, and ideally to develop a vaccine to prevent the development of chronic HCV.
PDF
