慢性C型肝炎干擾素治療病患體內低粒線體去氧核醣核酸複製數目與病毒反應度逆相關之研究

背景:慢性C型肝炎一直以來都是肝病治療上相當棘手的課題。目前慢性C型肝炎的標準治療處方為長效型干擾素(pegylated interferon)併用口服雷巴威林(Ribavirin)。自從此處方治療以來，已發現有諸多因素影響著治療效果。例如：年齡、肝臟纖維化程度、第一基因型之慢性C型肝炎等，依目前所採用的標準治療而言，上列因素均已證實和病毒治療的低反應度有關。在接受抗病毒治療的病人之中，本研究整合分析130位病患的臨床表現與生化資料，期望能在台灣中部的慢性C型肝炎的族群中，尋找出可預測其療效持續有效病毒反應(sustained virological response ，SVR ) 之重要因子。病人與方法: 共有130位在接受抗病毒治療之慢性C型肝炎病患納入本研究之中。除了傳統生物化學的資料分析之外，本研究測量了粒線體去氧核醣核酸之複製數目(copy number of mitochondrial DNA)，並以△Ct 來估算它的DNA氧化傷害。本研究收集彰化基督教醫院於2003年至2004年間所有接受長效型干擾素(pegylated interferon)併用口服雷巴威林(Ribavirin)治療之第一基因型之慢性C型肝炎病人的血液採樣，據以分析粒線體去氧核醣核酸之複製數目(copy number of mitochondrial DNA)與治療效果指標中之持續有效的病毒反應(SVR )的關聯性。結果: 在所分析的90位達到持續有效的病毒反應 (SVR)與40為病患未達到持續有效的病毒反應 (sustained virological response ，SVR) 的病患當中，我們發現治療前的年齡、性別、高血壓、高血脂與持續有效的病毒反應 (SVR)並無相關性存在。而在持續有效的病毒反應 (SVR)一組中，有較高的血色素(hemoglobin 14.74g/dL vs 13.97g/dL, p <0.05)與血小板(platelet count 180.97 vs 148.58, p <0.05)。而在持續有效的病毒反應 (SVR)一組中，第一基因型比例較低(65.89% vs 76.56%, p = 0.39 )。此外，在持續有效的病毒反應 (SVR)一組中，粒線體去氧核醣核酸之複製數目(copy number of mitochondrial DNA)明顯偏高(190.46 vs 138.83 , p < 0.05 )。至於△Ct則兩組明顯差異。結論: 在較差的持續有效的病毒反應 (SVR)的預測因子之中，除了傳統已知的因子之外，本研究發現粒線體去氧核醣核酸之複製數目(copy number of mitochondrial DNA)偏低與較差的持續有效的病毒反應 (SVR)有關。

關鍵字

C型肝炎；干擾素治療；粒線體

並列摘要

Background: Hepatitis C leads to serious to patients with chronic infection. Interferon based therapy is now the golden standard therapy for this chronic infection. Several factors such as old age, advanced liver fibrosis and genotype 1 hepatitis C infection are reported to be associated with decreased virological response to current standard therapy. We retrospectively analyze the clinical features and biological data of 130 patients received antiviral therapy in our institution and try to find out clinical factors to predict decreased SVR(sustained virological response) in our patient group. Material and Method: A total of 130 patients with chronic hepatitis C received antiviral therapy in our institution were included in our study. In addition to clinical biochemistry data, we measure the mitochondria DNA copy number and determine its oxidative DNA damage with △Ct in these patients. Result: 90 patients achieved sustained viral response (SVR) and 40 patients didn’t achieve SVR in this study. Clinical factors, such as age, sex, hypertension, hyperlipidemia are not associated with SVR in this cohort. Both higher hemoglobin level (14.74g/dL vs 13.97g/dL, p <0.05) and platelet count (180.97 vs 148.58, p <0.05) are found among the SVR group patients. The genotype 1 patients have a trend for lower SVR compared with non-genotype 1 patients (65.89% vs 76.56%, p = 0.39 ). A high mtDNA copy number is found in the SVR patient (190.46 vs 138.83 , p < 0.05 ). There is no difference of ?媒t between these two group of patients. Conclusion: In addition to traditional factors associated with decreased SVR in chronic hepatitis C patients. We found a low mtDNA copy number is also associated with decreased SVR in our patient group.

並列關鍵字

Hepatitis C ； interferon therapy ； mitochondria

參考文獻

1.Strader DB, Wright T, Th omas DL, Seeff LB (2004) Diagnosis,management, and treatment of hepatitis C. Hepatology 39:1147–71

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慢性C型肝炎干擾素治療病患體內低粒線體去氧核醣核酸複製數目與病毒反應度逆相關之研究

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