臺灣博碩士論文加值系統

背景：
C型肝炎是台灣很常見的疾病，但治療C型肝炎常因為藥物（干擾素和Ribavirin）的副作用而受限。臨床上最常見也最讓人困擾的副作用包括貧血、血小板低下和白血球數量減少。少數的國外研究顯示產生這些副作用的危險因子包括腎功能低下、高血壓、病毒基因型、基礎血色素值等。但目前在臨床治療病人時，並無明確的指標可以預測病人是否會產生這些副作用。
目的：
研究病人和疾病因子，包括氧化壓力和白血球粒線體DNA copy number，和C肝病人接受干擾素加雷巴威林治療後產生血液學副作用的關係。
方法：
本研究蒐集132位，介於40到60歲的C肝感染病人，用長效型干擾素加雷巴威林治療六個月，並在治療前、第一週、第二週、之後每個月收集血液學的資料。本研究定義嚴重血色素下降為治療期間血色素下降超過4g/dL，並收集病人本身的因子，包括白血球粒線體DNA copy number和delta Ct數值等，分析是否可能和病人有嚴重血色素下降或白血球、絕對嗜中性白血球、血小板下降比率有關。
結果：
有72位病人有嚴重血色素下降，60位沒有。比較兩組病人，高creatinine數值跟嚴重血色素下降有關(0.94±0.18 vs. 0.87±0.19 mg/dL, P= 0.047)。尤其在genotype 1　Ｃ肝病毒感染的病人裡，慢性腎臟病分級大於或等於2級的病人，比較容易有嚴重血色素下降的情形(P= 0.02)。而白血球下降比率的嚴重程度，則跟慢性腎臟病分級(大於或等於二級)和病毒基因型第1型有關(48.9± 14.5 v.s. 54.5± 12.6 %, P = 0.019 以及 54.4±13.5 v.s. 48.0±13.0 %, P = 0.009)。
結論：
在C型肝炎病人接受長效型干擾素加雷巴威林治療期間，腎功能是一個明顯會影響血色素和白血球數值下降的因子。C型肝炎病毒基因型第一型，也是另外一個會影響白血球數值下降的因子。

Background:
The treatment effect of chronic hepatitis C (HCV) is often limited due to the adverse effects of interferon and ribavirin. Hemolytic anemia and hematological adverse effect may influence the treatment program. Previous studies documented Genotype I, hypertension, low baseline hemoglobin, and raised creatinine were factors associated with the development of hematological abnormalities.
Aims:
The study evaluate if some host factors, included oxidative stress and leukocyte mitochondrial DNA copy number before treatment are associated with severe hematological adverse effect in HCV patients treated with peginterferon plus ribavirin.
Methods:
132 patients who age between 40 to 60 years old were treated with peginterferon plus ribavirin for 6 months. We checked hemogram parameters at baseline, first week, second week, and then per month until treatment ended. We defined severe drop in hemoglobin levels as hemoglobin compared with baseline dropped more than 4 g/dL any time during treatment period without other bleeding event. The host factors included leukocyte mitochondrial DNA copy number and delta Ct were evaluated the possible association with severe drop in hemoglobin levels ( drop > 4g/dL) and WBC, ANC,Platelet drop ratio.
Results:
72 patients had drop > 4 g/dL in hemoglobin levels, and 60 patients did not. Compared the host factors of two groups, high creatinine levels (0.94 ± 0.18 vs. 0.87 ± 0.19 mg/dL, P= 0.047) were associated with severe drop in hemoglobin levels. In genotype 1 HCV infected patients, high CKD stage(=>2) also were associated with severe drop in hemoglobin levels(P= 0.02). Besides, high CKD stage(=>2) and genotype 1 HCV infection, also associated with the severity of WBC count decline. (48.9± 14.5 v.s. 54.5± 12.6 %, P = 0.019 and 54.4±13.5 v.s. 48.0±13.0 %, P = 0.009)
Conclusions:
Renal function is a significant host factor of severe drop in hemoglobin and WBC count levels in patients with HCV treated with peginterferon plus ribavirin. Genotype 1 HCV infection also is a factor of severe WBC decline.

英文縮寫 IV
中文摘要 V
英文摘要 VII
壹、導論 1
一、慢性C型肝炎感染與治療 1
1.治療慢性C型肝炎藥物對人體的副作用 1
2.預測治療副作用產生的因子 4
二、粒線體功能與白血球粒線體去氧核糖核酸拷貝數值 5
1.粒線體的功能與自由基 5
2.白血球粒線體去氧核糖核酸拷貝數值 6
3.MtDNA copy number 與疾病的關係 7
三、C型肝炎治療藥物與人體的粒線體功能 8
1.C型肝炎治療藥物副作用與粒線體功能的關係 8
貳、研究構想 9
參、研究材料與方法 10
一、病人的收集和排除 10
二、C型肝炎藥物產生血液學副作用的監測和定義 12
三、治療病人本身因子的收集和評估 14
四、病人的粒線體DNA copy number和?媒t的測定 16
五、統計方法 20
肆、結果 21
ㄧ、收案個數和基本資料 21
二、產生貧血副作用與病人和疾病因子之間的關係 23
三、產生白血球和絕對嗜中性白血球低下副作用與病人和疾病因子之間的關係 25
四、產生血小板低下副作用與病人和疾病因子之間的關係 26
五、產生血液學副作用與病人治療前氧化壓力和白血球粒線體DNA copy number的關係 27
伍、討論 28
一、C型肝炎治療與副作用的產生 28
二、貧血副作用與病人本身因子之間的關係 29
三、白血球和絕對嗜中性白血球低下副作用與病人和疾病因子之間的關係 32
四、血小板低下副作用與病人和疾病因子之間的關係 32
五、血液學副作用與病人治療前氧化壓力和白血球粒線體DNA copy number的關係 33
陸、結論 34
柒、參考文獻 35
捌、表 41
玖、圖 54
拾、附件 58
一、人體試驗委員會核淮函 58

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