Sofosbuvir treatment and hepatitis C virus infection

Hepatitis C virus(HCV) infection is a serious problem worldwide.The use of interferon-based therapy has made HCV eradication challenging.The recent appearance of direct-acting antiviral agents(DAAs) has changed HCV therapy.Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy.Furthermore,the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety.In particular,sofosbuvir,a nucleotide-based NS5 B inhibitor,prevents HCV RNA synthesis by acting as a "chain terminator".Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response.The current review summarizes the efficacy and safety of sofosbuvir therapy.

Hepatitis C virus protease inhibitor-resistance mutations: Our experience and review

Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT.Between February 2010 and April2013,278 patients infected with HCV were enrolled in this study.All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin.In addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients.In all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay.HCV RNA was measured using the COBAS TaqMan HCV test.RESULTS:Female patients were dominant in the PNALT group(P【0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P【0.01)and the sustained virologic response(SVR)rates(P【0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype.In HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P【0.05)and having an EVR(P【0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.CONCLUSION:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

Relationship between Helium Degassing of Cattle-Manure-Compost Adsorbents and Copper Ions Removal

This work was aimed to investigate the effect of helium degassing of cattle-manure-compost (CMC) based activated carbons on the adsorptive removal of copper ions from aqueous solution. Degassing temperatures were 500℃, 800℃ and 1000℃. Activated carbons were characterized according to surface chemistry and pore structures. Adsorption of copper ions was carried out using the conventional bottle-point technique to which the equilibrium data were correlated to Langmuir and Freundlich models. Results indicated that the uptake of copper ions could be well characterized by Langmuir model. It was found that the adsorption of copper ions decreased with significant decrease in surface area as a result of helium degassing at higher temperature. The increase of electron density on graphene layers offered higher affinity towards copper ions at lower equilibrium concentration. It was inferred that copper ions favorably adsorbed on mesopores at lower equilibrium concentration and switched to micropores at higher equilibrium concentration.

Effect of phosphorus fluctuation caused by river water dilution in eutrophic lake on competition between blue-green alga Microcystis aeruginosa and diatom Cyclotella sp.

Tega-numa （Lake Tega） is one of the eutrophic lakes in Japan. For the improvement of water quality in Lake Tega, the North- chiba Water Conveyance Channel was constructed in 2000, which transfer water from Tone River into the lake. After 2000, the dominant species of diatoms, mainly Cyclotella sp., have been replacing blue-green algae, mainly Microcystis aeruginosa in Lake Tega. This transition of dominant species would be due to the dilution, but the detail mechanism has not been understood yet. This study examined the relationship between phosphorus fluctuation caused by river water dilution to Lake Tega and dominance of algal species, M. aeruginosa or Cyclotella sp. based on the single-species and the mixed-species culture experiments. The single-species culture experiment showed that the half-saturation constant and uptake rate of phosphorus were one order lower and seven times higher for M. aeruginosa than those for Cyclotella sp. These findings implied that M. aeruginosa would possess a potential for the growth and survival over Cyclotella sp. in the phosphorus limited condition. The superiority of M. aeruginosa was reflected in the outcome of the mixed-species culture experiment, i.e., dominance of M. aeruginosa, even phosphorus concentration was lowered to 0.01 mg-P/L. Therefore, it could be concluded that the decrease in phosphorus concentration due to the river water dilution to Lake Tega would be interpreted as a minor factor for the transition of dominant species from M. aeruginosa to Cyclotella sp.