1、非酒精性脂肪性肝病的中藥治療胡欣 江蘇省中西醫(yī)結合醫(yī)院 內(nèi)分泌科內(nèi)容概要NAFLD的定義與流行病學NAFLD的危害NAFLD的治療NAFLD的定義與流行病學NAFLD是一種與胰島素抵抗和遺傳易感密切相關的代謝應激性肝損傷，疾病譜包括非酒精性單純性肝脂肪變、非酒精性脂肪性肝炎（NASH）、肝硬化和肝細胞癌（HCC）。NAFLD的定義與流行病學疾病定義NAFLD肝臟病理學和影像學改變與酒精性肝病相似，但無過量飲酒等導致肝脂肪變的其他原因，患者通常存在營養(yǎng)過剩、肥胖和 MetS相關表現(xiàn)非酒精性不飲酒或無過量飲酒史（過去12個月男性每周飲用乙醇210g，女性140g），未應用胺碘酮、甲氨蝶呤、他莫昔芬

2、、糖皮質激素等藥物，并排除基因3型丙型肝炎病毒（HCV）感染、肝豆狀核變性、自身免疫性肝炎、全胃腸外營養(yǎng)、乏脂蛋白血癥、先天性脂質萎縮癥、乳糜瀉等可以導致脂肪肝的特定疾病非酒精性脂肪肝變又稱單純性脂肪肝，是NAFLD的早期表現(xiàn)，大泡性或大泡為主的脂肪變累及 5%以上肝細胞，可以伴有輕度非特異性炎癥NASHNAFLD的嚴重類型，5%以上的肝細胞脂肪變合并小葉內(nèi)炎癥和肝細胞氣球樣變性。NAFLD相關肝硬化有肥胖癥、MetS、T2DM和（或）NAFLD病史的隱源性肝硬化世界范圍內(nèi)普通人群NAFLD發(fā)病率為28.01-52.341000人/年NAFLD是全球最常見的慢性肝病，普通成人NAFLD 患病率

3、介于 6.3%45%，其中10%30%為NASH中東和南美洲NAFLD患病率最高，非洲最低，包括中國在內(nèi)的亞洲多數(shù)國家 NAFLD 患病率處于中上水平（25%）NAFLD的定義與流行病學Younossi ZM, et al. Hepatology. 2016, 64:73-84.NAFLD的定義與流行病學Younossi Z, et al. Nat Rev Gastroenterol Hepatol. 2018,15(1):11-20.NAFLD的定義與流行病學Younossi ZM, et al. Hepatology. 2016, 64:73-84.NAFLD的定義與流行病學Younoss

4、i ZM, et al. Hepatology. 2016, 64:73-84.NAFLD的危害25%30%41%10%單純脂肪變17.6億脂肪肝炎5億肝硬化/肝細胞癌2億NAFLD并非良性病變，而是一種進展性疾病 Arab JP, et al. Annu Rev Pathol. 2018, 13:321-350.NAFLD的危害Adams LA, et al. Gut. 2017, 66(6):1138-1153.NAFLD的危害Younossi ZM, et al. Hepatology. 2016, 64:73-84.NAFLD的危害2017年NATURE雜志呼吁：應高度重視NAFLDN

5、AFLD的治療非藥物治療藥物治療NAFLD的治療非藥物治療藥物治療NAFLD的治療Weight loss generally reduces HS, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. A combination of a hypocaloric diet (daily reduction by 500-1,000 kcal) and moderate-intensity exercise is likely to provide the be

6、st likelihood of sustaining weight loss over time.Weight loss of at least 3%-5% of body weight appears necessary to improve steatosis, but a greater weight loss (7%-10%) is needed to improve the majority of the histopathological features of NASH, including fibrosis.Exercise alone in adults with NAFL

7、D may prevent or reduce HS, but its ability to improve other aspects of liver histology remains unknownYounossi ZM, et al. Hepatology. 2016, 64:73-84.NAFLD的治療非藥物治療藥物治療NAFLD的治療西藥治療中藥治療藥物治療NAFLD的西藥治療胰島素增敏劑格列酮類二甲雙胍01維生素E02減肥藥GLP-1RA奧利司他西布曲明03FXR受體激動劑04他汀類05大麻受體阻滯劑、抗氧化應激等06Kaser S, et al. Int J Clin Pra

8、c. 2010, 64: 968-83. NAFLD的西藥治療Rinella ME. JAMA. 2015, 313:2263-73.NAFLD的西藥治療Rotman Y, et al. Gut. 2017, 66(1):180-190.NAFLD的中藥治療小檗堿中藥方：扶正化瘀膠囊、利肝石榴八味散、降脂膠囊、護肝清脂片、健肝寶（云芝、丹參、五味子）、膽寧片、化痰祛濕湯、血府逐瘀湯、葛根芩連湯、四逆散等食物及其提取物：白藜蘆醇、佛手柑多酚、寧夏枸杞多糖、薯蕷皂苷、辣椒素、大蒜烯丙半胱氨酸、芍藥苷、二氫楊梅素、杠柳毒苷A、蘆丁等中藥：甘草酸、水飛薊素、珠子草、柴胡、苦參、丹參、黃芩、五味子、黃芪

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10、藥治療-小檗堿（BBR）Wei X, et al. Evid Based Complement Alternat Med. 2016;2016:3593951.NAFLD的中藥治療-小檗堿（BBR）Chang X, Gao X, et al. J Transl Med. 2016, 14:266. NAFLD的中藥治療-小檗堿（BBR）Sun Y, Gao X, et al. Br J Pharmacol. 2018, 175(2):374-387. NAFLD的中藥治療-小檗堿（BBR）NAFLD的中藥治療-小檗堿（BBR）NAFLD的中藥治療-小檗堿（BBR）Zhu X, Gao X, e

11、t al. Molecules. 2016, 21(10).pii: E1336.小檗堿調(diào)控肝臟糖脂代謝關鍵通路降低肝臟脂肪含量上調(diào)FGF21增加自噬降低線粒體功能亢進、減少氧化應激調(diào)節(jié)腸道菌群NAFLD的中藥治療-降脂膠囊Zhao Y, et al. J Transl Med. 2015, 13:174. NAFLD的中藥治療-降脂膠囊Zhao Y, et al. J Transl Med. 2015, 13:174. NAFLD的中藥治療-降脂膠囊Zhao Y, et al. J Transl Med. 2015, 13:174. NAFLD的中藥治療-降脂膠囊Zhao Y, et al.

12、 J Transl Med. 2015, 13:174. NAFLD的中藥治療-利肝石榴八味散Jiang Y, et al. J Ethnopharmacol. 2015, 176:499-507.NAFLD的中藥治療-利肝石榴八味散Jiang Y, et al. J Ethnopharmacol. 2015, 176:499-507.NAFLD的中藥治療-利肝石榴八味散Jiang Y, et al. J Ethnopharmacol. 2015, 176:499-507.NAFLD的中藥治療-利肝石榴八味散Jiang Y, et al. J Ethnopharmacol. 2015, 176:499-507.NAFLD的中藥治療-利肝石榴八味散Jiang Y, et al. J Ethnopharmacol. 2015, 176:499-507.NAFLD的中藥治療-中藥提取物Zhao Y, et al. J Transl Med. 2015, 13:174. NAFLD的中藥治療-五味子1. Zhu PL, et al. Drug Des Devel Ther. 2015, 9:923-35.2. Jang MK, et al. J Ethnopharmacol. 2016, 185:96-104. 總結NAFLD是一種與胰島素抵抗和遺傳易感密切相關的代謝應激性肝損傷，