Preventing and treating hepatitis B infection.
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ABSTRACT:
SUBMITTER: Aggarwal R
PROVIDER: S-EPMC526122 | biostudies-literature | 2004 Nov
REPOSITORIES: biostudies-literature
Publications
Preventing and treating hepatitis B infection.
Aggarwal Rakesh R Ranjan Piyush P
BMJ (Clinical research ed.) 20041101 7474
Similar Datasets
Project description:Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-alpha and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection.
| S-EPMC2217617 | biostudies-other
Project description:Globally, hepatitis E virus (HEV) causes significant morbidity and mortality each year. Despite this burden, there are no specific antivirals available to treat HEV patients, and the only licensed vaccine is not available outside China. Ribavirin and alpha interferon are used to treat chronic HEV infections; however, severe side effects and treatment failure are commonly reported. Therefore, this study aimed to identify potential antivirals for further development to combat HEV infection. We selected 16 compounds from the nucleoside and nonnucleoside antiviral classes that range in developmental status from late preclinical to FDA approved and evaluated them as potential antivirals for HEV infection, using genotype 1 replicon luminescence studies and replicon RNA quantification. Two potent inhibitors of HEV replication included NITD008 (half-maximal effective concentration [EC50], 0.03 μM; half-maximal cytotoxic concentration [CC50], >100 μM) and GPC-N114 (EC50, 1.07 μM, CC50, >100 μM), and both drugs reduced replicon RNA levels in cell culture (>50% reduction with either 10 μM GPC-N114 or 2.50 μM NITD008). Furthermore, GPC-N114 and NITD008 were synergistic in combinational treatment (combination index, 0.4) against HEV replication, allowing for dose reduction indices of 20.42 and 8.82 at 50% inhibition, respectively. Sofosbuvir has previously exhibited mixed results against HEV as an antiviral, both in vitro and in a few clinical applications; however, in this study it was effective against the HEV genotype 1 replicon (EC50, 1.97 μM; CC50, >100 μM) and reduced replicon RNA levels (47.2% reduction at 10 μM). Together these studies indicate drug repurposing may be a promising pathway for development of antivirals against HEV infection.
| S-EPMC6535575 | biostudies-literature
Project description:Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection.
| S-EPMC4911897 | biostudies-literature
Project description:INTRODUCTION: Infections can impact the reproductive health of women and hence may influence pregnancy related outcomes for both the mother and the child. These infections range from sexually transmitted infections (STIs) to TORCHS infections to periodontal disease to systemic infections and may be transmitted to the fetus during pregnancy, labor, delivery or breastfeeding. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Preconception behavioral interventions significantly declines re-infection or new STI rates by 35% (95% CI: 20-47%). Further, condom use has been shown to be the most effective way to prevent HIV infection (85% protection in prospective studies) through sexual intercourse. Intervention trials showed that preconception vaccination against tetanus averted a significant number of neonatal deaths (including those specifically due to tetanus) when compared to placebo in women receiving more than 1 dose of the vaccine (OR 0.28; 95% CI: 0.15-0.52); (OR 0.02; 95% CI: 0.00-0.28) respectively. CONCLUSION: Preconception counseling should be offered to women of reproductive age as soon as they test HIV-positive, and conversely women of reproductive age should be screened with their partners before pregnancy. Risk assessment, screening, and treatment for specific infections should be a component of preconception care because there is convincing evidence that treatment of these infections before pregnancy prevents neonatal infections.
| S-EPMC4196562 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-03 | GSE182765 | GEO
Project description: Not available
| S-EPMC9215332 | biostudies-literature
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| S-EPMC8406455 | biostudies-literature
Project description:BACKGROUND & AIMS: This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. METHODS: Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG2000-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. RESULTS: A siRNA combination (terms “siHBV”) with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log10 reduction) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4+ and CD8+ T cell responses by expressed mIL-2 protein. CONCLUSIONS: By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.
2024-04-02 | GSE262515 | GEO
Project description:Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.
| S-EPMC7190892 | biostudies-literature
Project description:BackgroundPressure ulcers affect approximately 10% of people in hospitals and older people are at highest risk. A correlation between inadequate nutritional intake and the development of pressure ulcers has been suggested by several studies, but the results have been inconsistent.ObjectivesTo evaluate the effects of enteral and parenteral nutrition on the prevention and treatment of pressure ulcers.Search methodsIn March 2014, for this first update, we searched The Cochrane Wounds Group Specialised Trials Register, the Cochrane Central register of Controlled Trials (The Cochrane Library), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library), the Health Technology Assessment Database (HTA) (The Cochrane Library), the Cochrane Methodology Register (The Cochrane Library), NHS Economic Evaluation Database (The Cochrane Library), Ovid Medline, Ovid Embase and EBSCO CINAHL. No date, language or publication status limits were applied.Selection criteriaRandomised controlled trials (RCTs) evaluating the effects of enteral or parenteral nutrition on the prevention and treatment of pressure ulcers, which measured the incidence of new ulcers, ulcer healing or changes in pressure ulcer severity. There were no restrictions on types of patient, setting, date, publication status or language.Data collection and analysisTwo review authors independently screened for inclusion, and disagreement was resolved by discussion. Two review authors independently extracted data and assessed quality using the Cochrane Collaboration tool for assessing risk of bias.Main resultsWe included 23 RCTs, many were small (between 9 and 4023 participants, median 88) and at high risk of bias.Eleven trials compared a combination of nutritional supplements, consisting of a minimum of energy and protein in different dosages, for the prevention of pressure ulcers. A meta-analysis of eight trials (6062 participants) that compared the effects of mixed nutritional supplements with standard hospital diet found no clear evidence of an effect of supplementation on pressure ulcer development (pooled RR 0.86; 95% CI 0.73 to 1.00; P value 0.05; I(2) = 13%, random effects). This outcome is at unclear or high risk of bias.Fourteen trials evaluated the effects of nutritional supplements on the healing of existing pressure ulcers: seven trials examined mixed nutritional supplements, three the effects of proteins, two trials examined zinc, and two studies examined ascorbic acid. The included trials were heterogeneous with regard to participants, interventions, comparisons and outcomes and meta-analysis was not appropriate. There was no clear evidence of an improvement in pressure ulcer healing from the nutritional supplements evaluated in any of these individual studies.Authors' conclusionsThere is currently no clear evidence of a benefit associated with nutritional interventions for either the prevention or treatment of pressure ulcers. Further trials of high methodological quality are necessary.
| S-EPMC9736772 | biostudies-literature