Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial

Furusyo, Norihiro; Ogawa, Eiichi; Sudoh, Masayuki; Murata, Masayuki; Ihara, Takeshi; Hattori, Takeo; Ikezaki, Hiroaki; Hiramine, Satoshi; Mukae, Haru; Toyoda, Kazuhiro; Taniai, Hiroaki; Okada, Kyoko; Kainuma, Mosaburo; Kajiwara, Eiji; Hayashi, Jun

doi:10.1016/j.jhep.2012.08.003

Cited by 53 publications

(35 citation statements)

References 24 publications

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“…We and others subsequently showed that SERMs could also inhibit viral entry and virion production (12,29), indicating that SERMs may interfere with multiple steps of the viral life cycle. In this sense, raloxifene, a SERM which displays anti-HCV activity in cell culture (36), ameliorates the cure rates when used in combination with IFN-␣ and ribavirin in postmenopausal women (37), suggesting that this class of inhibitors may have some therapeutic value in combination with other antivirals. In this study, we focused our attention on hydroxyzine and benztropine, which are benzhydrylcontaining compounds with antihistaminic properties.…”

Section: Discussionmentioning

confidence: 99%

Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine

Mingorance

Friesland

Coto‐Llerena

et al. 2014

Antimicrob Agents Chemother

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cHepatitis C virus (HCV) infection is a major biomedical problem worldwide as it causes severe liver disease in millions of humans around the world. Despite the recent approval of specific drugs targeting HCV replication to be used in combination with alpha interferon (IFN-␣) and ribavirin, there is still an urgent need for pangenotypic, interferon-free therapies to fight this genetically diverse group of viruses. In this study, we used an unbiased screening cell culture assay to interrogate a chemical library of compounds approved for clinical use in humans. This system enables identifying nontoxic antiviral compounds targeting every aspect of the viral life cycle, be the target viral or cellular. The aim of this study was to identify drugs approved for other therapeutic applications in humans that could be effective components of combination therapies against HCV. As a result of this analysis, we identified 12 compounds with antiviral activity in cell culture, some of which had previously been identified as HCV inhibitors with antiviral activity in cell culture and had been shown to be effective in patients. We selected two novel HCV antivirals, hydroxyzine and benztropine, to characterize them by determining their specificity and genotype spectrum as well as by defining the step of the replication cycle targeted by these compounds. We found that both compounds effectively inhibited viral entry at a postbinding step of genotypes 1, 2, 3, and 4 without affecting entry of other viruses.

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Section: Discussionmentioning

confidence: 99%

Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine

Mingorance

Friesland

Coto‐Llerena

et al. 2014

Antimicrob Agents Chemother

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“…Using the propensity score in the program of SPSS Statistics version 22.0, cases of treatment with simeprevir were matched to those of treatment with telaprevir. To fulfill the ignorable treatment assignment assumption for the propensity score method, we included the following variables with a known association to treatment outcome: HCV RNA level, fibrosis status (FIB‐4 index), IL28B SNP, and prior treatment response . Fundamental background factors such as age, sex, BMI, ALT, and eGFR, were also included to improve the precision of the analysis.…”

Section: Methodsmentioning

confidence: 99%

Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non‐cirrhotic patients with chronic hepatitis C virus genotype 1b infection

Ogawa

Furusyo

Kajiwara

et al. 2015

J of Gastro and Hepatol

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“…However, other studies have shown that suppression of estrogen signaling reduces the incidence of HCC development in HCV carriers. Using selective estrogen modulators (SERM), researchers have shown that estrogen signaling interferes with the HCV viral cycle (Murakami, et al 2013) and reduces HCV-mediated Toll-Like receptor 7 (TOLR7) signals (Fawzy, et al 2012), indicating that SERM are potential adjuvant antiviral treatments (Furusyo, et al 2012). Interestingly, Huang et al reported that male gender was an independent risk factor for the development of liver disease in patients with HCV-related hepatitis (Huang, et al 2011).…”

Section: Part I Androgen/ar Signaling In Non-cancerous Liver Diseasesmentioning

confidence: 99%

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

Lung¹,

Lai²,

Yeh³

et al. 2014

Endocrine-Related Cancer

145

114

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Summary Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of non-cancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.

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Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial

Cited by 53 publications

References 24 publications

Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine

Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine

Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non‐cirrhotic patients with chronic hepatitis C virus genotype 1b infection

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

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