A Phase 2a, Open-label, Randomized Study of the Safety and Preliminary Efficacy of Triple or Quadruple Combination DAAs With Ultra-short Duration Therapy in Subjects With HCV Genotype 1b Infection (YANGTZE Study)

This is a phase 2a, open-label, randomized study. The study is designed to test the hypothesis that the nucleoside inhibitor sofosbuvir combined with NS5A inhibitor daclatasvir and NS5B non-nucleoside inhibitor CDI-31244 with/without the protease inhibitor asunaprevir will result in high SVR rate with a shortened treatment duration (2 weeks) in non-cirrhotic HCV genotype 1b-infected subjects.

开始日期2019-05-01

申办/合作机构

Humanity & Health Medical Group Limited

NCT03723824 / Terminated临床4期IIT

An Open-label, Cohort Study of Grazoprevir/Elbasvir Combination Therapy for Patients With Genotype 1b Chronic Hepatitis C After Liver or Kidney Transplantation

Grazoprevir/elbasvir combination therapy is highly effective in the treatment of genotype 1b chronic hepatitis C, and the drug-drug interaction with central immunosuppressant, such as tacrolimus, should be manageable. The aim of this study is to assess the efficacy and tolerability of grazoprevir/elbasvir combination therapy in treating genotype 1b chronic hepatitis C after liver or kidney transplantation.

开始日期2019-02-14

申办/合作机构

Taichung Veterans General Hospital

[+1]

NCT03485846 / Completed临床2期

Multicenter, Open-label, Phase II Safety and Efficacy Study of All-oral Combination Narlaprevir/Ritonavir and Daclatasvir Administered for 12 Weeks in Patients With Genotype 1b Chronic Hepatitis C

The purpose of this study is to confirm that combination of Narlaprevir, Ritonavir and Daclatasvir is safe and highly effective regimen in treatment-naїve patients with chronic hepatitis C (HCV) genotype 1b infection.

开始日期2017-11-27

申办/合作机构

R-Pharm JSC

[+1]

100 项与慢性丙型肝炎基因型 1b 相关的临床结果

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100 项与慢性丙型肝炎基因型 1b 相关的转化医学

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0 项与慢性丙型肝炎基因型 1b 相关的专利（医药）

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项与慢性丙型肝炎基因型 1b 相关的文献（医药）

2024-11-01·Journal of Infection

IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C

Article

作者: Pfeiffer, Ruth M ; Prokunina-Olsson, Ludmila ; Lai, Jennifer B. ; O'Brien, Thomas R. ; Witt, David J ; Baker, Francine S ; Witt, David J. ; O'Brien, Thomas R ; Morrissey, Kerry Grace ; Saxena, Varun ; Lai, Jennifer B ; Baker, Francine S. ; Chen, Sabrina ; Pfeiffer, Ruth M.

BACKGROUNDShorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success.METHODSAmong 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics.RESULTSOverall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4-TT/TT genotype (1.8%), those with HCV RNA <5.8 log₁₀ copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years.CONCLUSIONApplying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries.

2024-11-01·Journal of Hepatology

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals

Article

作者: Choi, In Ah ; Koh, June-Young ; Lee, Eun Young ; Park, Su-Hyung ; Lee, Ha Seok ; Ko, Yun Yeong ; Jung, Min Kyung ; Shin, Eui-Cheol ; Kim, Won ; Lee, Jeong Seok ; Kim, Hyung-Don ; Park, Jun Yong ; Lee, Dong Hyeon ; Jeong, Hye Won ; Kim, So-Young ; Choi, Seong Jin

BACKGROUND & AIMSChronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment.METHODSPatients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis.RESULTSThe Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance.CONCLUSIONSOverall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection.IMPACT AND IMPLICATIONSDuring chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

2024-02-01·Free Radical Biology and Medicine

Impact of amino acid substitutions in hepatitis C virus core region on the severe oxidative stress

Article

作者: Chida, Takeshi ; Kawata, Kazuhito ; Ito, Masahiko ; Suda, Takafumi ; Suzuki, Tetsuro ; Watanabe, Shinya ; Noritake, Hidenao ; Ohta, Kazuyoshi

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, leading to liver steatosis, fibrosis, and hepatocellular carcinoma (HCC). Despite the accumulation of clinical data showing the impact of amino acid substitutions at positions 70 (R70Q/H) and/or 91 (L91M) in the HCV core protein in progressive liver diseases, including HCC, the underlying mechanisms have not been elucidated. We analyzed 72 liver biopsy specimens from patients with chronic HCV genotype 1b (HCV-1b) infection prior to antiviral treatment. Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear factor erythroid 2-related factor 2 (NRF2) in the nucleus were quantified using liver tissue immunohistochemistry. The effects of amino acid substitutions in the HCV core region on hepatocellular oxidative stress were investigated using wild-type or double-mutant (R70Q/H+L91M) HCV-1b core transfection and stable expression in human hepatoma HuH-7 cells. Overall, 24, 19, 11, and 18 patients had the wild-type, R70Q/H, L91M, and R70Q/H+L91M genotypes, respectively, in the HCV core. A significantly higher accumulation of hepatocellular 8-OHdG and a lower NRF2/8-OHdG ratio were observed in patients with R70Q/H+L91M than in those with the wild-type disease. Increased levels of intracellular superoxide and hydrogen peroxide in the cytoplasm and mitochondria, mRNA expression of enzymes generating oxidative stress, and nuclear expression of nicotinamide adenine dinucleotide phosphate oxidase 4 were augmented in cells treated with R70Q+L91M. HCV core proteins harboring either or both substitutions of R70Q/H or L91M enhanced hepatocellular oxidative stress in vivo and in vitro. These amino acid substitutions may affect HCC development by enhancing hepatic oxidative stress in patients with chronic HCV-1b infection.