scholarly journals Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes

Hepatology ◽  
2011 ◽  
Vol 54 (5) ◽  
pp. 1570-1579 ◽  
Author(s):  
Meital Gal-Tanamy ◽  
Larisa Bachmetov ◽  
Amiram Ravid ◽  
Ruth Koren ◽  
Arie Erman ◽  
...  
2017 ◽  
Vol 26 (4) ◽  
pp. 381-386
Author(s):  
Mircea Manuc ◽  
Carmen M. Preda ◽  
Corneliu P. Popescu ◽  
Cristian Baicuș ◽  
Theodor Voiosu ◽  
...  

Background & Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania.Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address.Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanța (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramureș (8.8/105) (p<0.001).Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.Abbreviations: BMI: body mass index; DAA: direct-acting antiviral agent; GT: genotype; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; IDU: intravenous drug users; MELD: model for end stage liver disease; NASH: non-alcoholic steatohepatitis; SVR; sustained virologic response.


2020 ◽  
Vol 19 (4) ◽  
pp. 389-393
Author(s):  
Nobuhiro Fujita ◽  
Akihiro Nishie ◽  
Yoshiki Asayama ◽  
Kousei Ishigami ◽  
Tomohiro Nakayama ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 223 ◽  
Author(s):  
Sara Sobhy Kishta ◽  
Reem El-Shenawy ◽  
Sobhy Ahmed Kishta

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.


Medicine ◽  
2018 ◽  
Vol 97 (12) ◽  
pp. e0172 ◽  
Author(s):  
Mohamed Ahmed Abdel-Mohsen ◽  
Ahlam Abd-Allah El-Braky ◽  
Abeer Abd El-Rahim Ghazal ◽  
Mohammed Mohammed Shamseya

2021 ◽  
pp. 227-238
Author(s):  
Asako Murayama ◽  
Takanobu Kato

2019 ◽  
Vol 20 (9) ◽  
pp. 2367 ◽  
Author(s):  
Amiram Ravid ◽  
Noa Rapaport ◽  
Assaf Issachar ◽  
Arie Erman ◽  
Larisa Bachmetov ◽  
...  

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3β-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.


2002 ◽  
Vol 76 (16) ◽  
pp. 8189-8199 ◽  
Author(s):  
Valérie Castet ◽  
Chantal Fournier ◽  
Alexandre Soulier ◽  
Rozenn Brillet ◽  
Joliette Coste ◽  
...  

ABSTRACT Chronic hepatitis C is a common cause of liver disease, the complications of which include cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis C is based on the use of alpha interferon (IFN-α). Recently, indirect evidence based on mathematical modeling of hepatitis C virus (HCV) dynamics during human IFN-α therapy suggested that the major initial effect of IFN-α is to block HCV virion production or release. Here, we used primary cultures of healthy, uninfected human hepatocytes to show that: (i) healthy human hepatocytes can be infected in vitro and support HCV genome replication, (ii) hepatocyte treatment with IFN-α results in expression of IFN-α-induced genes, and (iii) IFN-α inhibits HCV replication in infected human hepatocytes. These results show that IFN-α acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-α.


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