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研究生:蔡宏斌
研究生(外文):Hung-Bin Tsai
論文名稱:C型肝炎病毒活性對長期血液透析患者營養不良發炎反應複合症候群之短期影響
論文名稱(外文):The short-term influence of hepatitis C virus activity on malnutrition-inflammation complex syndrome in maintenance hemodialysis patients
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2008
畢業學年度:96
語文別:英文
論文頁數:36
中文關鍵詞:C型肝炎病毒活性營養不良發炎反應症候群血液透析尿毒症相關食慾不良
外文關鍵詞:hepatitis Cvirus activitymalnutrition-inflammation complex syndrome (MICS)hemodialysisuremia-associated anorexia
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背景:雲嘉地區是台灣C型肝炎與末期腎臟病高盛行率區域,在此區的血液透析患者通常有較高罹患C型肝炎與心血管疾病的危險。希望藉此研究來了解C型肝炎對血液透析患者之發炎反應與營養的短期影響,並提供更多資訊有助於C型肝炎整體防治策略。

研究目標:我們認為C型肝炎血液透析患者具有獨特的新陳代謝與全身發炎反應特性,能與臨床不良狀況作連結,也會導致臨床上較高心血管併發症的發生。

研究設計:本研究為一前瞻性追蹤研究,進行於嘉義市某一區域教學醫院,完整收集171位規則血液透析(包含76位C型肝炎血液透析患者)的臨床資料與發炎性生物標記特性。胰島素阻抗定義根據HOMA胰島素阻抗指數而營養不良發炎反應計分表用以記錄營養不良發炎反應症候群的嚴重程度。病人的食慾與營養狀態應用食慾與營養狀態評量表及上臂中圍測量來作整合性評估。血液透析患者的全身發炎狀態以高敏感度C反應蛋白來測量。C肝病毒的基因型與病毒RNA以聚合酶連鎖反應測定。我們使用上臂中圍、主觀營養評估和食慾與營養評分表來測量病人七個月的營養狀況變化。預後評估以前瞻性追蹤血液透析患者七個月營養不良發炎反應計分表分數變化。
結果: 171位長期透析病人追蹤七個月後,58位C肝抗體陽性與至少一次HCV-RNA陽性(HCV-RNA titers > 50 IU/mL)患者歸為活性C肝組,18位C肝抗體陽性但兩次HCV-RNA陰性為不活動C肝組, 其餘95位C肝抗體陰性者為非C肝組。在活性C肝組中,51人(87.9%)有持續性C肝病毒血症,7人(12.1%)有間歇性C肝病毒血症, 當中44.8%為genotype 1b, 31%為genotype 2a.。活性與不活動C肝組病人經歷透析期間均較非C肝組為久(64.0±54.1 month vs. 67.9±54.0 vs. 42.3±36.0 month, P <0.05)。第一與第七個月比較皆發現活性C肝組在肝功能指數為三組中最高但三酸甘油酯為最低。經過七個月追蹤並分析營養不良發炎反應計分表細項,活性C肝組較非C肝組病人在共病症狀態(1.6±0.8 vs. 1.7±0.7, P <0.05)、血清白蛋白指標(1.1±0.8 vs. 0.7±0.7 P < 0.05)、肌肉萎縮程程度(1.6±0.8 vs. 1.3±0.8, P <0.05)與體脂肪含量(0.5±0.7 vs. 0.3±06, P <0.05)有明顯差異且總分較高(MIS score: 6.9±4.0 vs. 5.3±3.3, P<0.05).。以廣義估計方程式(GEE)模式作回歸分析,在校正C肝病毒活性、性別、中央化年紀、中央化身體質量指數、透析後體重、食慾狀態、標準化蛋白質代謝率、嚴重腦血管疾病後發現活性C肝感染為營養不良發炎反應複合症候群之顯著獨立危險因子(β= 0.82, P <0.05, CI= 0.16-1.49)。

結論: 本研究證實C型肝炎病毒感染為臺灣長期血液透析患者營養不良發炎反應複合症候群之獨立危險因子。營養不良發炎反應計分表可以作為C肝血液透析患者短期臨床預後之有效評估工具。

關鍵詞:
C型肝炎、病毒活性、營養不良發炎反應症候群、血液透析、尿毒症相關食慾不良
Background: High prevalence of hepatitis C virus (HCV) infection and end-stage renal disease is noticed in Yunlin, Chiayi area in Taiwan. Patients with maintenance hemodialysis (MHD) in this area have the highest risk for HCV infection and cardiovascular disease. Understanding the natural history of HCV and its association with inflammation, nutrition and outcomes in dialysis patients may provide more information for anti-HCV management strategies in dialysis and other patient populations.

Objective: We hypothesize that HCV infected MHD patients have distinct metabolic and inflammatory characteristics that can be linked to malnutrition-inflammation complex syndrome (MICS) and leads to higher clinical complications.

Design: A prospective longitudinal study was conducted in one regional teaching hospital during Sept. 2007 to March 2008. A cohort of 171 MHD patients including 76 HCV subjects was recruited. Basic data and dialysis characteristics were collected. Anti-HCV antibody was detected with a third-generation enzyme immunoassay while HCV genotype and viral load were analyzed by polymerase chain reaction twice in the first and last month. Insulin resistance was defined by HOMA-IR index. Nutritional and appetite status were evaluated by appetite and diet assessment tool and anthropometric evaluation. Inflammatory status was measured by high sensitivity C-reactive protein. Outcome evaluation was based on malnutrition-inflammation score to rate the severity of MICS in first month and followed prospectively at the seventh month.
Results: Of 171 enrolled patients, 58 having anti-HCV positive with at least one positive HCV-RNA titer (HCV RNA > 50 IU/mL) were categorized as active HCV group, 18 anti-HCV positive with two negative HCV-RNA titers as inactive HCV group, 95 negative anti-HCV titers as non-HCV group. Active HCV group had 51 (87.9%) persistent and 7 (12.1%) intermittent HCV viremia patients with 44.8% genotype 1b and 31% genotype 2a. Active and inactive HCV group experienced longer dialysis vintage then non-HCV group (64.0±54.1 month vs. 67.9±54.0 vs. 42.3±36.0 month, P <0.05). Serum triglyceride level was lowest and GPT level was highest in active HCV group during the first and seventh month. After 7 months follow-up, Active HCV group had significant difference from non-HCV group in MIS component as co-morbidity (1.6±0.8 vs. 1.7±0.7, P <0.05), albumin index (1.1±0.8 vs. 0.7±0.7, P <0.05), muscle wasting (1.6±0.8 vs. 1.3±0.8, P<0.05), decreased fat stores (0.5±0.7 vs. 0.3±0.6, P<0.05) and higher total MIS score (6.9±4.0 vs. 5.3±3.3, P<0.05). After adjustment of HCV activity, sex, centered age and body mass index, posthemodialysis weight, appetite status, normalized protein catabolic rate, severe cerebrovascular accident, marginal regression analysis by GEE model denoted HCV infection as a significant independent predictor of MICS (β= 0.82, P <0.05, CI= 0.16-1.49).

Conclusions: This study proves active HCV infection as an independent predictor of MICS in Taiwanese MHD patients. MIS can be used as an assessment tool to evaluate the short-term clinical outcome in HCV-MHD patients.

Key words: Hepatitis C, virus activity, malnutrition-inflammation complex syndrome (MICS), hemodialysis, uremia-associated anorexia
口試委員會審定書..........................................i
誌謝.....................................................ii
中文摘要................................................iii
Abstract..................................................v
Index...................................................vii
Lists of Tables and Appendix.............................ix
Introduction..............................................1
Materials and Methods.....................................2
(1)Study population......................................2
(2) Malnutrition-inflammation score......................3
(3) Appetite and diet assessment.........................4
(4) Anthropometric evaluation............................4
(5) Laboratory assessment................................4
(6) Statistical analysis.................................6
Results...................................................7
Discussion...............................................10
(1) HCV prevalence of MHD patients in Southern Taiwan...10
(2) HCV and malnutrition in MHD patients................11
(3) HCV and systemic inflammation in MHD patients.......12
(4) HCV infection and reverse epidemiology..............13
(5) HCV and iron status in MHD patients.................13
(6) Active and inactive HCV infection versus insulin
resistance in MHD patients..........................13
(7) Implications and future directions..................14
(8) Study limitations...................................15
(9) Conclusion..........................................15
Acknowledgements.........................................16
References...............................................16
Table 1..................................................20
Anti-HCV positivity, viremia and genotypes among the 171
patients in the first month and seventh month follow-up
Table 2-1................................................21
Geographic, hematologic, biochemical data, dialysis
parameters, nutritional markers of all patients in the
first month
Table 2-2................................................24
Geographic, hematologic, biochemical data, dialysis
parameters, nutritional markers of all patients after
seven months follow-up
Table 3-1................................................27
Components of malnutrition-inflammation score between
active HCV, inactive HCV and non-HCV patients in the first
month
Table 3-2................................................28
Components of malnutrition-inflammation score between
active HCV, inactive HCV and non-HCV patients in the
seventh month
Table 4..................................................29
Marginal regression analysis of factors influence
malnutrition-inflammation score in maintenance
hemodialysis patients during seven months using the GEE
method
Figure 1.................................................30
Possible factors affect malnutrition-inflammation complex
syndrome in maintenance hemodialysis patients
Appendix 1...............................................31
Components of Comprehensive Malnutrition- inflammation
Score (MIS) (in English)
Appendix 2...............................................33
Comprehensive Malnutrition-inflammation Score Sheet (in
Chinese)
Appendix 3...............................................35
Appetite and Diet Assessment Tool Charlson Co-morbidity
Index
Appendix 4...............................................36
Will HCV activity increase malnutrition and inflammation
burden in maintenance hemodialysis patients?
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