Natural interferon-beta treatment for patients with chronic hepatitis C in Japan

Sasaki, Reina; Nakamoto, Shingo; Haga, Yuki; Nakamura, Masato; Yasui, Shin; Jiang, Xia; Wu, Shuang; Arai, Makoto; Yokosuka, Osamu

doi:10.4254/wjh.v7.i8.1125

Cited by 12 publications

(10 citation statements)

References 63 publications

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“…The use of immunostimulatory compounds is increasingly common, as well. For example, recombinant cytokines like IFN-α and IFN-β are used to modulate the immune response to chronic hepatitis B and hepatitis C viruses, while TLR7 agonists are used in cancer immunotherapy [5][6][7]. Promisingly, both lyophilized bacteria and bacterial lysates have been shown to effectively prevent bacterial infection [8], although these treatments occurred prior to exposure.…”

Section: Introductionmentioning

confidence: 99%

Novel Immune Modulators EnhanceCaenorhabditis elegansResistance to Multiple Pathogens

Hummell

Revtovich

Kirienko

2020

Preprint

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Traditionally, treatments for bacterial infection have focused on killing the microbe or preventing its growth. As antimicrobial resistance becomes more ubiquitous, attention has begun to shift toward disrupting the host-pathogen interaction by improving the host defense. Using a high-throughput, fragment-based screen to identify compounds that alleviate Pseudomonas aeruginosa-mediated killing of Caenorhabditis elegans, we identified over 20 compounds that stimulated host defense gene expression. Five of these molecules were selected for further characterization. Four compounds showed little toxicity against mammalian cells or worms, consistent with their identification in a phenotypic, high-content screen. Each of the compounds activated several host defense pathways, but the pathways were generally dispensable for compound-mediated rescue in Liquid Killing, suggesting redundancy or that the activation of one or more unknown pathways may be driving compound effects. A genetic mechanism was identified for LK56, which required the Mediator subunit MDT-15/MED15 and NHR-49/HNF4 for its function. Interestingly, LK32, LK34, LK38, and LK56 also rescue C. elegans from P. aeruginosa in an agar-based assay, which uses different virulence factors and defense mechanisms. Rescue in an agar-based assay for LK38 entirely depended upon the PMK-1/p38 MAPK pathway. Three compounds, LK32, LK34, and LK56 also conferred resistance to Enterococcus faecalis, and the two lattermost, LK34 and LK56, also reduced pathogenesis from Staphylococcus aureus. This study supports a growing role for MDT-15 and NHR-49 in immune response and identifies 5 molecules that with significant potential for use as tools in the investigation of innate immunity.

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Section: Introductionmentioning

confidence: 99%

Novel Immune Modulators EnhanceCaenorhabditis elegansResistance to Multiple Pathogens

Hummell

Revtovich

Kirienko

2020

Preprint

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“…The treatment of hepatitis C for many years was carried out using a combination based on pegylated interferon-alpha (IFN), conjugated with ribavirin (RBV) (Coppola & Pisaturo, 2015). IFN-based treatment had hepatocytes and lymphocytes as target cells acting through IFN receptors on the cell surface, inducing a response through their receptors, with activation of stimulated interferon genes (ISGs) and antiviral effects (Sasaki, 2015). However, a significant part of human cells has IFN receptors on their surface.…”

Section: Treatment Of Chronic Hcv Diseasementioning

confidence: 99%

Clinical and epidemiological overview of liver fibrosis and hepatocellular carcinoma in patients infected with the hepatitis C virus

Farias

Macedo

et al. 2020

RSD

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About 2.4 million people die each year worldwide as a result of chronic infection with the hepatitis C virus (HCV). HCV is a worldwide problem, more than 170 million people are infected with the virus worldwide, corresponding to about 3% of the population. Some common signs for patients chronically infected with HCV are: increased liver enzyme activity and chronic liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma. The present study consists of a literature review, of a qualitative nature which aims to approach the main clinical and epidemiological aspects of the chronic infection caused by the HCV. HCV detection is carried out by screening for antibodies by enzyme-linked immunosorbent assay (ELISA) and screening for HCV-RNA through polymerase chain reaction (PCR). The current detection methods are not viable for all medical centers and outpatient clinics, making it necessary to develop new detection methods, since the technological apparatus for screening HCV-RNA, as well as ELISA, is a distant reality for the vast majority of the global health system. The development of direct-acting antivirals (DAAs) increased the viral response, reaching up to 92.7% success rate. It is necessary to monitor post-treatment patients, as well as to treat patients who are still affected by the virus worldwide, to ensure that there is no progression of liver fibrosis in cirrhosis, nor the development of HCC. Additionally, vigilance should be maintained for possible mutations and the emergence of viral resistance to DAAs.

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“…Type I interferons bind to a common cell surface receptor, resulting in the activation of the Jak-STAT signal transduction system[30]. Interferon-β may be important not only to prevent patients with acute hepatitis C from developing chronic infection[31] but also to reduce the risk of HCC[32]. After DAA treatment, the expression levels of interferon-β, interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) significantly decreased and rapidly normalized at EOT in the peripheral blood mononuclear cells (PBMCs)[29].…”

Section: Change In Cytokines and Chemokines In Hcc Occurrence And Recmentioning

confidence: 99%

Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

Sasaki

Kato

Yokosuka

et al. 2018

WJH

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The introduction of a direct-acting antiviral (DAA) for patients with hepatitis C virus (HCV) infection, could lead to higher sustained virologic response (SVR) rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma (HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.

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Natural interferon-beta treatment for patients with chronic hepatitis C in Japan

Cited by 12 publications

References 63 publications

Novel Immune Modulators EnhanceCaenorhabditis elegansResistance to Multiple Pathogens

Novel Immune Modulators EnhanceCaenorhabditis elegansResistance to Multiple Pathogens

Clinical and epidemiological overview of liver fibrosis and hepatocellular carcinoma in patients infected with the hepatitis C virus

Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

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