2026-08-08 14:44
參考資料: 全聯會-醫師繼續教育-糖尿病、脂肪肝、與慢性腎病的關係及照護(影片時間：46分4秒)
DM患者 70 % 有 fatty liver
過去脂肪肝的分類. 先區分酒精或非酒精成因. 等於先看病患是否喝酒. 先貼上一個酒癮標籤. 再者 fatty 英文還有肥胖的意思. 脂肪肝患者不一定肥胖. 所以目前建議將脂肪肝英文名稱以 Metabolic dysfunction-associated steatotic liver disease(MASLD發音同muscle) . 其中 steatotic 是病理學的脂肪. 與肥胖區隔開來. (中文的肥胖與脂肪是不同意思.所以中文稱脂肪肝較不具歧意.
美國本土研究, 脂肪肝會增加全因死亡率.
下面是人體切片. 可以看出內臟脂肪與皮下脂肪顯著差異
脂肪肝造成肝硬化機轉
脂肪堆積在細胞內. 脂肪造成細胞脹起(ballooned吹氣球). 細胞內產生很多脂肪球. 脂肪會影響細胞內粒線體. 脂肪毒性造成細胞死亡. 人體修復肝臟過程會引來下圖四種細胞. 其中 Stellate cell 星狀細胞轉化為肌成纖維細胞. 反覆發炎-修復過程最後導致肝纖維化與肝硬化
好心肝會刊 肝星狀細胞（Hepatic Stellate Cell, HSC）在肝硬化的形成過程中扮演關鍵角色，當肝臟長期受損或慢性發炎時，原本靜止的星狀細胞會被活化，轉變為會製造大量膠原蛋白的肌成纖維細胞，進而導致肝纖維化與肝硬化。
abnormal liver function test 確實可以預測是否罹患DM
ALT 與脂肪肝關聯性較高. ALT高的患者有較高機率發生DM
(AST與酒精肝比較有關係)
胰島素阻抗+ 高胰島素血症 使得肝臟發生 TG堆積.
脂肪肝慢性發炎過程會產生很多發炎因子. 也會引起DM
下圖紅線代表沒有肥胖但有脂肪肝. 發生DM機率較正常人高.
最上面黑線代表又胖又有脂肪肝. 發生DM機率又更高
這些是可以預測肝細胞內脂肪堆積的指標
BMI高. 腰圍. ALT上升 TG高 GGT高 FPG或DM. ferritin上升. insulin or HOMA-IR
評估胰島素阻抗 HOMA-IR胰島素，由胰臟的貝他細胞所分泌，是身體中唯一可以降低血糖的荷爾蒙，胰島素在身體裡的作用就像一把鑰匙，會把細胞的門打開，讓血中的葡萄糖進入細胞成為能量來源，當分泌不足時，血糖就會升高。胰島素阻抗，說穿了就是胰島素的訊號不良，胰島細胞便會代償性的分泌更多胰島素，就好像當對方聽不清楚，我們就講話講得更大聲，所以當身體對胰島素產生阻抗的時候，空腹時的胰島素便會比正常狀況下來得更高，利用此原理，1985年Matthews 等人提出了homeostatic model assessment (HOMA)來評估胰島素阻抗(insulin resistance)，稱作HOMA-IR
脂肪導致的肝臟胰島素阻抗以及肝發炎. 原本胰島素會促進肝臟將血中葡萄糖轉化為肝醣儲存在肝臟. 肝細胞對胰島素反應下降. 使得肝臟無法有效轉化血中葡萄糖. 而增加發生DM機率.
最近遇到幾個脂肪肝患者. 有一些個案(無DM)自費使用 SGLT2 inhibitor, 一個使用 jardiance. 另一個使用 Canagliflozin (可拿糖/Invokana)
查詢了一下脂肪肝與 SGLT2 inhibitor 的文獻.
MASH= metabolic dysfunction-associated steatohepatitis 非酒精性脂肪肝炎
參考資料1
uptodate -Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults 節錄裡面一段關於 forxiga 的敘述
脂肪肝炎患者使用安慰劑. 20% 纖維化會自然改善. 8% 肝指數會改善
Dapagliflozin – The sodium-glucose cotransporter 2 inhibitor dapagliflozin improves liver histology in patients with MASH. In a randomized trial of 154 patients with biopsy-proven MASH of any fibrosis stage, dapagliflozin 10 mg daily for 48 weeks resulted in improvement in fibrosis without worsening of steatohepatitis compared with placebo (45 versus 20 percent) [52]. MASH resolved without worsening of fibrosis in 23 versus 8 percent.
參考資料2
這篇統合分析(或稱薈萃分析)收錄的臨床研究使用的藥物是 dapagliflozin (Forxiga)(n = 5篇), empagliflozin(Jardiance) (n = 4篇), and ipragliflozin(台灣沒有. 主要是日本及美國使用) (n = 2篇)
The efficacy of sodium-glucose transporter 2 inhibitors in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis
Abstract
The efficacy of sodium-glucose transporter 2 (SGLT-2) inhibitors for nonalcoholic fatty liver disease (NAFLD) is unclear. Therefore, we conducted a systematic review and meta-analysis to evaluate SGLT-2 inhibitors efficacy for NAFLD treatment. We systematically searched major electronic databases (PubMed, Cochrane Library, Web of Science, Embase) from inception until 11/2023, identifying randomized controlled trials (RCTs) of SGLT-2 inhibitors treatment for patients with NAFLD. The mean differences (MD or SMD) and 95 % confidence intervals (CIs) were calculated via random-effects models. Eleven articles (n = 805 patients with NAFLD) were included in this study. Of these, 408 participants received SGLT-2 inhibitors, while 397 participants were in the control group. SGLT-2 inhibitors significantly reduced liver enzyme levels, including aspartate alanine aminotransferase (ALT) (MD [95 % CI]; −9.31 U/L [-13.41, −5.21], p < 0.00001), aspartate aminotransferase (AST) (MD [95 % CI]; −6.06 U/L [-10.98, −1.15], p = 0.02), and gamma-glutamyltransferase (GGT) (MD [95 % CI]; −11.72 U/L [-15.65, −7.80], p < 0.00001). SGLT-2 inhibitors intervention was also associated with significant reductions in body weight (MD [95 % CI]; −2.72 kg [-3.49, −1.95], p < 0.00001) and BMI (MD [95 % CI]; −1.11 kg/m2 [-1.39, −0.82], p < 0.00001) and improvements in glycaemic indices, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). However, no significant changes in total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) were observed. The meta-analysis revealed a beneficial effect of SGLT-2 inhibitors on liver functions and body weight, BMI, TG, HDL-C, and glucose homeostasis in patients with NAFLD, indicating that SGLT-2 inhibitors might be a clinical therapeutic strategy for these patients, especially individuals with concurrent type 2 diabetes mellitus (T2DM).
