Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy (sIFN-pred2) (sIFN-pred2)
Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort (Second Phase)
調査の概要
詳細な説明
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.
研究の種類
入学 (予想される)
連絡先と場所
研究場所
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Jilin
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Changchun、Jilin、中国、130061
- 募集
- First Hospital Jilin University
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コンタクト:
- Yu Pan, PhD/MD
- 電話番号:0431-88782120
- メール:panyu20000@yahoo.com.cn
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コンタクト:
- Xiumei Chi, PhD/MD
- 電話番号:0431-88782222
- メール:xiumeichi@hotmail.com
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主任研究者:
- Yu Pan, PhD/MD
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
- Serum HCV-RNA > 3 log IU/ml
- Has been infected by HCV for more than 6 months
- ALT,AST have been elevated continuously, inflammation and necrosis have been observed according to the histology diagnosis (G>=2),modest liver fibrosis (S>=2)For those patients whose ALT are normal,treatment accord to the liver biopsy. If obvious fibrosis has been detected (S2,S3),treatment should be done.For those S0,S1 stage patients, treatment could be delayed, but ALT/AST should be assayed every 3-6 months.
- Compensated liver disease
- Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin
Exclusion Criteria:
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History:
- Has history of decompensated liver diseases
- Has been treated with other anti-virus drugs,or anti-tumor drugs,immuno-suppression drugs
- Has a history of autoimmune hepatitis
- History of a severe seizure disorder or current anticonvulsant use
- History or other evidence of a medical condition associated with chronic liver disease other than HCV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
- Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
- History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
Current condition:
- Pregnant women or women during the lactation period
- Co-infected with hepatitis b virus or human immunodeficiency virus
- Liver cancer or alpha-fetoprotein > 100ng/ml
- Blood neutrophils count < 1500/mm3, or platelets count < 90000/mm3
- Female hemoglobin <11.5g/dL, male hemoglobin <12.5g/dL
- Blood creatinine > 1.5 ULN
- Have severe mental diseases,especially depression
- Severe pulmonary dysfunction
- Severe cardiovascular disease
- Uncontrolled diabetes
- Uncontrolled thalassemia
- Evidence of alcohol abuse (alcohol consumption>40 g/day)
- Unwillingness to provide informed consent or abide by the requirements of the study
- Local or System malignancy unstable status
研究計画
研究はどのように設計されていますか?
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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インターフェロンとリバビリン
すべての患者は標準的な治療プロトコルに従いました。
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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.
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Absolute Blood HCV RNA Copies at designed time points
時間枠:0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
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Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.
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0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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HCV 遺伝子型
時間枠:ベースライン
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HCV NS5A は T ベクターにクローン化され、進化分析のために配列決定されます。
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ベースライン
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薬物乱用歴
時間枠:ベースライン
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患者には薬物使用歴について尋ねられます。
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ベースライン
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IL-28B多型
時間枠:ベースライン
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IL28遺伝子多型、rs8099917、rs12979860など
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ベースライン
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Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)
時間枠:Baseline,4wk,12wk,24wk,48wk
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ALT AST are assayed to detect the hepatic function.
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Baseline,4wk,12wk,24wk,48wk
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Fibrosis stage
時間枠:Baseline,4wk,12wk,24wk,48wk
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Fibrosis is analyzed with Fibroscan.
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Baseline,4wk,12wk,24wk,48wk
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Regular blood test
時間枠:Baseline,4wk,12wk,24wk,48wk
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The distribution and absolute count of the different types of blood cells are assayed.
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Baseline,4wk,12wk,24wk,48wk
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Electrocardiography
時間枠:Baseline,4wk,12wk,24wk,48wk
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Electrocardiography is taken to avoid severe side effects.
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Baseline,4wk,12wk,24wk,48wk
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Alcohol ,smoking condition
時間枠:Baseline,4wk,12wk,24wk,48wk
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Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.
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Baseline,4wk,12wk,24wk,48wk
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協力者と研究者
スポンサー
捜査官
- スタディチェア:Bing Sun, Doctor、Chinese Academy of Sciences
- スタディディレクター:Chen Yang, Doctor、Chinese Academy of Sciences
出版物と役立つリンク
一般刊行物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2012ZX10002007
- 2009ZX10004-105-jida02 (その他の助成金/資金番号:Ministry of Science and Technology)
- 2008ZX10002-014-jida02 (その他の助成金/資金番号:Ministry of Science and Technology)
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