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| ID | Type | Description | Link |
|---|---|---|---|
| 2009ZX10004-105-jida02 | Other Grant/Funding Number | Ministry of Science and Technology | |
| 2008ZX10002-014-jida02 | Other Grant/Funding Number | Ministry of Science and Technology |
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| Name | Class |
|---|---|
| Chinese Academy of Sciences | OTHER_GOV |
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The purpose of this study is to validate the first round HCV early dynamics discovery within a larger population.
Hepatitis C virus (HCV) infection rate in China is about 3%, which means about 30 million patients. Combination therapy of ribavirin and interferons (IFN) is the standard clinical treatment of HCV chronical infections. However, overall rate of sustained virological response (SVR) still do not exceed 60% even with ribavirin and peg-IFN. Due to several virus- and patient-related factors, treatment is even less successful in certain populations, especially in HCV genotype 1 infection. Thus the standard therapy duration is optimized according to the virus genotype in the clinical practice. Nowadays, two direct antiviral agents (DAAs) have been approved by Food and Drug Administration (FDA) of USA this year, which increases the SVR rate. However, high price, side effects and long duration render people to hesitate about the addition of the third drug in the traditional prescription.
Predicting the outcome of traditional therapy is the cornerstone of the personalized therapy for HCV infected patients. In order to obtain an accurate prediction, different methods have been tried. Several indicators have been suggested to predict the final treatment outcomes. Rapid Virus Response (RVR), which indicates the non-detectable virus at the forth week since therapy starts, has been used to predict the final treatment outcome.Other indicators, including virus genotype, host genotype of IL-28B, human race and interferon stimulated genes (ISG) expression have also been shown to relate to and be able to predict the treatment outcomes to some extent. Here the investigators propose that the HCV virus dynamics analysis will give a more precise prediction for the therapy outcome.
The general idea is that blood HCV titration data is obtained continuously in the early treatment period (first 2 weeks) of the patients who have strictly followed the therapy method. These titration data will be used to draw virus dynamics curve and calculate the corresponding parameters individually. The parameter(s) that can distinguish patients who reach the therapy evaluation standard from those who failed to reach the evaluation standard will be selected out, and such parameter(s) may be used to predict the therapy outcome of a new patient in the early stage of his/her treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interferon and ribavirin | All the patients followed the standard treatment protocol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| interferon alpha 2b | Drug | Interferon:dosage,5 million units/person;frequency,every other day (qod);duration,48 weeks;Subcutaneous injection. Ribavirin: dosage,15mg/kg/day;frequency,three times a day (t.i.d);duration,48 weeks;take orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Blood HCV RNA Copies at designed time points | Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test. | 0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk |
| Measure | Description | Time Frame |
|---|---|---|
| IL-28B polymorphism | IL28 gene polymorphism,rs8099917,rs12979860,etc | Baseline |
| HCV genotype | HCV NS5A is cloned into T vector and sequenced for evolutionary analysis. |
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Inclusion Criteria:
Exclusion Criteria:
-
History:
Current condition:
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Patients are from the northeast of China. Most of the patients have been infected by the hepatitis c virus due to the drug abuse. Many of them share the same syringe for drug intravenous injection. However, HIV infection has been rarely detected.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chen Yang, PhD | Contact | +8615221296266 | yangch@zoho.com | |
| Xiumei Chi, PhD | Contact | +862154921375 | xiumeichi@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Bing Sun, Doctor | Chinese Academy of Sciences | Study Chair |
| Chen Yang, Doctor | Chinese Academy of Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First Hospital Jilin University | Recruiting | Changchun | Jilin | 130061 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9756471 | Background | Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103. | |
| 17596864 | Background | Dahari H, Ribeiro RM, Perelson AS. Triphasic decline of hepatitis C virus RNA during antiviral therapy. Hepatology. 2007 Jul;46(1):16-21. doi: 10.1002/hep.21657. |
| Label | URL |
|---|---|
| Coperator's Homepage | View source |
Not provided
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| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D008107 | Liver Diseases |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| D000077190 | Interferon alpha-2 |
| ID | Term |
|---|---|
| D016898 | Interferon-alpha |
| D007370 | Interferon Type I |
| D007372 | Interferons |
| D016207 | Cytokines |
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Blood serum,Peripheral blood mononuclear cells (PBMC)
|
| Baseline |
| Alanine Aminotransferase (ALT) and Aspartate transaminase (AST) | ALT AST are assayed to detect the hepatic function. | Baseline,4wk,12wk,24wk,48wk |
| Fibrosis stage | Fibrosis is analyzed with Fibroscan. | Baseline,4wk,12wk,24wk,48wk |
| Regular blood test | The distribution and absolute count of the different types of blood cells are assayed. | Baseline,4wk,12wk,24wk,48wk |
| Electrocardiography | Electrocardiography is taken to avoid severe side effects. | Baseline,4wk,12wk,24wk,48wk |
| Alcohol ,smoking condition | Patients are asked whether they take alcohol or smoke cigarettes during the therapy period. | Baseline,4wk,12wk,24wk,48wk |
| Drug abuse history | Patients will be asked about their drug usage history. | Baseline |
| 20463660 | Background | Snoeck E, Chanu P, Lavielle M, Jacqmin P, Jonsson EN, Jorga K, Goggin T, Grippo J, Jumbe NL, Frey N. A comprehensive hepatitis C viral kinetic model explaining cure. Clin Pharmacol Ther. 2010 Jun;87(6):706-13. doi: 10.1038/clpt.2010.35. Epub 2010 May 12. |
| 15602565 | Background | Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS. Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature. 2004 Dec 16;432(7019):922-4. doi: 10.1038/nature03153. |
| 11583749 | Background | Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5. |
| 21111740 | Background | Dill MT, Duong FH, Vogt JE, Bibert S, Bochud PY, Terracciano L, Papassotiropoulos A, Roth V, Heim MH. Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology. 2011 Mar;140(3):1021-31. doi: 10.1053/j.gastro.2010.11.039. Epub 2010 Nov 25. |
| 20738775 | Background | Araujo ES, Dahari H, Neumann AU, de Paula Cavalheiro N, Melo CE, de Melo ES, Layden TJ, Cotler SJ, Barone AA. Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients. J Viral Hepat. 2011 Apr;18(4):e52-60. doi: 10.1111/j.1365-2893.2010.01358.x. |
| Homepage of Jilin University | View source |
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D036341 |
| Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |