Then and now: The progress in hepatitis B treatment over the past 20 years

Marzio, Dina Halegoua-De; Hann, Hie‐Won

doi:10.3748/wjg.v20.i2.401

Cited by 50 publications

(37 citation statements)

References 97 publications

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“…Most of these treatments are for chronic viral infections such as HIV and hepatitis C (Das and Arnold, 2013a, b; Flint SJR, 2015b; Halegoua-De Marzio and Hann, 2014; Manns and von Hahn, 2013). The necessity for and dearth of effective and approved treatments for acute viral infections was on full display after the Ebola outbreak in West Africa in 2014.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis

et al. 2017

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Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA). Inhibition of p70 S6 kinase through rapamycin treatment reduced viral titers in vitro and increased survival and mitigated clinical disease in RVFV challenged mice. Additionally, the phosphorylation of p70 S6 kinase was decreased following rapamycin treatment in vivo. Collectively these data demonstrate modulating p70 S6 kinase can be an effective antiviral strategy.

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Section: Discussionmentioning

confidence: 99%

Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis

et al. 2017

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“…Currently, 90% hepatitis B vaccine is effective in preventing hepatitis B virus (HBV) infection, but >700,000 deaths still occur worldwide as a consequence of HBV infection [75]. Patients with chronic HBV infection are currently treated with antiviral agents such as tenofovir and entecavir together with immunomodulators like IFN-α 2b, but side effects and viral resistance limit the effectiveness of these therapies [76]. In this regard, RNAi is considered a potentially attractive treatment for HBV infection.…”

Section: Therapeutic Applications Of Sirna and Target Genesmentioning

confidence: 99%

Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines

Park

Pei

et al. 2016

Advanced Drug Delivery Reviews

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Small interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bioconjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. However, most cases address local applications or diseases in the filtering organs, reflecting remaining challenges in systemic delivery of siRNA. The difficulty in siRNA delivery is in large part due to poor circulation stability and unfavorable pharmacokinetics and biodistribution profiles of siRNA. This review describes the pharmacokinetics and biodistribution of siRNA nanomedicines, focusing on those reported in the past 5 years, and their pharmacological effects in selected disease models such as hepatocellular carcinoma, liver infections, and respiratory diseases. The examples discussed here will provide an insight into the current status of the art and unmet needs in siRNA delivery.

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“…We have seen great progress in the prevention, diagnosis, and treatment of hepatitis B in the past few decades; however, we are far from eradicating or even eliminating the disease (4). The production of the first hepatitis B vaccine in 1983, which was called the first anti-cancer vaccine by the world health organization (WHO) (4), offered hope in controlling and preventing the disease.…”

Section: Contextmentioning

confidence: 99%

“…The production of the first hepatitis B vaccine in 1983, which was called the first anti-cancer vaccine by the world health organization (WHO) (4), offered hope in controlling and preventing the disease. The outlook was further enhanced by the production and development of the first antiviral drugs in later years.…”

Section: Contextmentioning

confidence: 99%

“…In other words, the infection remained. In addition, facts such as medical costs, drug adverse effects, drug resistance, and treatment failure have made controlling hepatitis B more challenging (4). All currently available oral drugs must be consumed indefinitely, which carries significant costs and is associated with low patient compliance (4).…”

Section: Contextmentioning

confidence: 99%

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Hepatitis B and its Relationship With Oxidative Stress

Alavian

Showraki

2016

Hepat Mon

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ContextDespite the great breakthroughs we have witnessed in the last 50 years in the prevention, diagnosis, and treatment of hepatitis B, we are still far from eradicating or even curing the disease. Achieving further progress in controlling this disease will not be possible without discovering the exact pathogenesis behind it. One prime suspect in the pathogenesis of various diseases is oxidative stress. This review will exclusively explore hepatitis B in the context of oxidative stress to obtain a more comprehensive clinical perspective on its pathogenesis and eventual medical therapy.Evidence AcquisitionWe systematically searched PubMed, Google Scholar, Web of Science, EMBASE, and Scopus using an extensive list of keywords in the following three categories: 1) Hepatitis B and oxidation 2) Hepatitis B and antioxidant system 3) Effects of approved anti-hepatitis B drugs on redox status. All relevant articles were obtained and reviewed carefully after the exclusion criteria were deployed.ResultsThere is great evidence indicating extensive oxidative stress occurs in hepatitis B. This oxidative stress takes place on multiple levels, including lipid peroxidation, DNA oxidation, protein oxidation, and reactive oxygen and nitrogen species production. However, there are also conflicting results with regard to antioxidant therapy and antioxidant status in hepatitis B, some of which may be explained by the concept of “compensatory gaps.” Nevertheless, further studies are indicated to reach a more thorough judgment.ConclusionsDespite the presence of vast oxidative stress in hepatitis B, antioxidant therapy is not always effective as a treatment strategy, especially considering that antioxidants can act as “double-edged swords” or antioxidants; if not used at the right time or place or in the right combination, these substances can easily become pro-oxidants. Therefore, several studies will be needed to determine suitable antioxidant therapies. We propose the “2-step Combined Antioxidant Adjuvant Therapy for hepatitis B (2CAAT Hep B)” as a new strategy for antioxidant adjuvant therapy. We also suggest developing an international platform and database for antioxidant adjuvant therapy in hepatitis B (IPAATH and IDAATH) to canalize this field of research in a standardized direction, especially when complexity is a problem.

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Then and now: The progress in hepatitis B treatment over the past 20 years

Cited by 50 publications

References 97 publications

Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis

Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis

Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines

Hepatitis B and its Relationship With Oxidative Stress

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