| 摘要: | 肥胖是異常或過度脂肪堆積，已被視為全球公共衛生挑戰。治療肥胖的方式包含調整飲食與生活習慣、藥物介入及減重手術。而與非手術介入相比，減重手術對於減重及改善相關併發症最具效果。代謝相關性脂肪肝病(metabolic dysfunction-associated fatty liver disease, MAFLD)是 2020年國際共識提出的新概念，與以往的非酒精性脂肪肝疾病診斷標準有顯著差異。代謝相關性脂肪肝病致病機轉尚未完全明瞭，目前以多重打擊假說解釋致病機制。肝纖維化的機轉多而複雜，以TGF-β1訊號路徑最為人所知。在臨床上代謝相關性脂肪肝病缺乏準確且平價的評估工具，也缺乏非侵入性生物標記物作為診斷參考。故本研究以尋找預測性生物標記作為輔助診斷代謝相關性脂肪肝病為目的進行。本次研究以病態性肥胖患者於減重手術取得的肝臟組織進行肝臟組織學判讀，共納入50位病人，分別為10位肝臟正常組、19位無或輕度纖維化之脂肪肝炎組及21位顯著纖維化之脂肪肝炎組。研究發現術後六個月的體位測量、生化數值及影像學結果等數據相較於術前，顯示出較佳的肝臟功能，脂肪肝及肝纖維化消退。SMAD3、pSMAD3及α-SMA在肝臟表現與肝纖維化程度具有顯著正相關。脂質體分析發現將DG 34:1及TG 52:3結合APRI可作為預測性生物標記並且可輔助診斷MAFLD纖維化嚴重程度。
Obesity, characterized by abnormal or excessive fat accumulation, is recognized as a global public health challenge. Common strategies for weight loss and management include dietary adjustments, lifestyle modifications, pharmacological therapies, and bariatric surgery. Bariatric surgery has demonstrated superior effectiveness in achieving weight reduction and alleviating associated complications compared to non-surgical methods. Metabolic dysfunction-associated fatty liver disease (MAFLD), introduced as a new concept in 2020, diverges notably from previous diagnostic criteria of non-alcoholic fatty liver disease. The underlying mechanisms of MAFLD, often explained by the multiple-hit hypothesis, remain incompletely understood. Liver fibrosis, a critical concern, involves complex pathways such as the TGF-β1 signaling pathway. However, current clinical tools for MAFLD assessment lack accuracy and cost-effectiveness, particularly in non-invasive biomarkers for diagnostic purposes. Therefore, this study aimed to identify predictive biomarkers to aid in the diagnosis of MAFLD. Liver histopathology from morbidly obese patients undergoing bariatric surgery was analyzed. A total of 50 patients were included: 10 with normal liver histology, 19 with steatohepatitis without or mild fibrosis, and 21 with steatohepatitis with significant fibrosis. Results indicated improved liver function, regression of hepatic steatosis, and reduction in liver fibrosis at six months post-surgery compared to pre-surgery levels. Significant positive correlations were observed between liver expression of SMAD3, pSMAD3, α-SMA, and the severity of liver fibrosis. Lipidomic analysis identified the relative abundance of DG 34:1 and TG 52:3 in combination with APRI as predictive biomarkers promising biomarkers to assist in assessing the severity of fibrosis in MAFLD. |
