透過您的圖書館登入
IP:216.73.216.62
  • 學位論文

嚴重肥胖患者非酒精性脂肪肝病之相關研究

Nonalcoholic Fatty Liver Disease in Severely Obese Patients

指導教授 : 余明隆

摘要


研究背景: 隨著肥胖盛行率的增加,非酒精性脂肪肝炎(nonalcoholic steatohepatitis)將成為嚴重的公共衛生問題,而病態性肥胖患者更是非酒精性脂肪肝炎之高危險群。單純脂肪肝被視為良性狀態且較不會進展為嚴重肝病,但研究顯示約10-29%的非酒精性脂肪肝炎病患在10年內會進展成肝硬化。由於限制於需要作肝切片才能鑑別患者是否為單純脂肪肝或是有非酒精性脂肪性肝炎,目前亞洲國家對病態性肥胖患者非酒精性脂肪肝炎之研究很少。由於臺灣病態性肥胖患者接受減重手術案例快速增加且可施行術中肝切片檢查,這使得我們有機會對這個議題做更深入之探討。 研究目的:  探討嚴重肥胖患者非酒精性脂肪肝炎之盛行率及減重手術後非酒精性脂肪肝病之變化  探討單核苷酸多型性是否和嚴重肥胖患者之非酒精性脂肪肝炎相關  探討嚴重肥胖患者非酒精性脂肪肝炎之危險因子及建立嚴重肥胖患者非酒精性脂肪肝炎之臨床非侵入性的預測模式 研究對象與方法: 本計劃以接受減重手術之嚴重肥胖患者為對象,紀錄病人之臨床資料和生化數值,並施行術中經皮肝切片檢查。我們收集185位患者之術前血液和術中肝組織。此外,我們也分析21位接受術中肝切片及術後一年肝切片之患者,以比較減重手術對非酒精性脂肪肝病的影響。 結果: 我們有以下四點發現  接受減重手術之嚴重肥胖患者非酒精性脂肪肝病和非酒精性脂肪肝炎之盛行率分別為83.2%和50.8%。  減重手術可明顯改善嚴重肥胖患者之非酒精性脂肪肝病。  PPARGC1A rs8192678 GA/AA genotype和PNPLA3 rs738409 GG genotype 會有加乘性增加嚴重肥胖患者非酒精性脂肪肝炎之機會。  我們建立一個以身體質量指數、肝指數和三酸甘油脂為主之臨床評分系統來預測嚴重肥胖患者發生非酒精性脂肪肝炎之機會。

並列摘要


Background: With the increasing prevalence of obesity, nonalcoholic steatohepatitis (NASH) will become an important issue of public health and morbidly obese patients are especially the high-risk group of NASH. Simple steatosis is thought to be a benign status but about 10 to 29% of individuals with NASH develop cirrhosis within 10 years. Liver biopsy is still the gold standard for the differential diagnosis between simple steatosis and NASH, however, it is an invasive procedure which limit the research of NASH in morbidly obese patients. More and more morbidly obese patients undergo bariatric surgery and also receive intra-operative liver biopsy in Taiwan, and this provides an opportunity for us to approach this issue. Aims:  To investigate the prevalence of NASH in severely obese Taiwanese patients and to evaluate the effect of bariatric surgery on nonalcoholic fatty liver disease (NAFLD)  To test whether the single nucleotide polymorphisms are associated with NASH in severely obese Taiwanese patients  To identify the risk factors of NASH and to build a scoring system to predict NASH in severely obese Taiwanese patients Materials and Methods: This study enrolls severely obese patients undergoing bariatric surgery in E-Da hospital. Preoperative data including demographic information, anthropometric measurements and biochemical data were collected and liver biopsy was done intra-operatively. One hundred and eighty-five subjects were enrolled and their blood samples and liver specimens were collected. We also enrolled twenty-one morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy one year after laparoscopic Roux-en-Y gastric bypass to evaluate the effect of bariatric surgery on NAFLD. Results:  The prevalence of NAFLD and NASH in severely obese Taiwanese undergoing bariatric surgery was 83.2% and 50.8%, respectively.  Bariatric surgery can achieve a dramatic improvement of NAFLD, both biochemically and histologically in morbidly obese Taiwanese patients.  The PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype had a synergistic effect on NASH in severely obese Taiwanese patients.  A simple clinical scoring system incorporating BMI, ALT, and triglyceride can predict NASH in severely obese Taiwanese patients.

參考文獻


1. Harrison SA, Kadakia S, Lang KA, Schenker S. Nonalcoholic steatohepatitis: what we know in the new millennium. Am J Gastroenterol 2002;97:2714-24.
2. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31.
3. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122:1649-57.
4. Clark JM, Alkhuraishi AR, Solga SF, Alli P, Diehl AM, Magnuson TH. Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. Obes Res 2005;13:1180-6.
5. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011;332:1519-23.

延伸閱讀