Non-alcoholic Fatty Liver Disease: A Review for the Pathogenic Mechanism and Management

非酒精性脂肪肝病：致病機轉及治療回顧

林瑞瑤(Jui-Yao Lin) ； 鄭啟清(Kee-Ching Jeng) ； 黃彼得(Pi-Deh Haung) ； 彭洸萍(Kuang-Ping Peng)

《童綜合醫學雜誌》 12卷1期 (2018/06) Pp. 6-19

摘要

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease associated with metabolic syndrome worldwide. Patients with NAFLD are typically obese; however, nonobese individuals are also affected. NAFLD can vary from benign macrovesicular hepatic steatosis to more severe nonalcoholic steatohepatitis (NASH), hepatic fibrosis, liver cirrhosis, and hepatocellular carcinoma. Pathogenic mechanisms underlying NAFLD include multiple metabolic factors associated with obesity, insulin resistance, gut microbiota, ceramide, and genetics. Asymptomatic NAFLD can slowly progress to NASH and end-stage liver disease that requires liver transplantation. NAFLD/NASH are diagnosed based on abnormal liver chemistry, imaging studies, and liver biopsy. Fatty liver impairs regeneration and induces secondary replicative pathways, wherein proliferation of hepatic progenitor cells during chronic hepatocyte injury is followed by ductular reaction, leading to periportal fibrogenesis. Therefore, fibrosis score is a useful parameter for evaluating the severity of NASH. Current treatments of NAFLD/NASH include lifestyle modification for weight loss as well as treatment with vitamin E, thioglitazones, the antioxidant silymarin, farnesoid X receptor (FXR) agonists, and antifibrotic antibodies. Gut microbiota play an important role in NAFLD, illustrated by an increase in serum lipopolysac-charide (LPS) and liver Toll-like receptor 4 (TLR4) in animal models of NAFLD, and supplementation with probiotics reduces both indices and improve pathological lesions in these animal models. However, the therapeutic effect of these treatments in NAFLD/NASH await further studies.

關鍵字

Non-alcoholic fatty liver disease ； Non-alcoholic steatohepatitis ； Pathogenic mechanism ； Treatments

並列摘要

非酒精性脂肪肝病(NAFLD) 是與代謝癥候症相關的最常見慢性肝病，普遍見於全世界。雖然脂肪肝病人中，普遍是屬過度肥胖，但亦有非肥胖者。NAFLD 依照其嚴重程度可分為脂肪肝、脂肪性肝炎(non-alcoholic steatohepatitis ，NASH) 、肝纖維化、肝硬化、肝癌。其致病機轉包括代謝相關的體重過重、糖尿病、神經醯胺(ceramide) 過度產生、腸道細菌及基因等。無症狀的脂肪肝會慢慢形成脂肪肝炎，導致肝病末期，需要移植肝臟的治療。診斷脂肪肝病需做肝功能生化檢查、影像檢查及取肝生檢體切片。由於脂肪肝阻擾再生功能，引發肝前驅細胞增生反應，也導致門脈纖維化的反應，因此肝切片纖維化指數，可以評估脂肪性肝炎NASH 的嚴重度。目前治療NAFLD/NASH 方法，包括調整生活習慣、控制體重、補充維生素E 、降血脂藥、降血糖藥、降膽汁藥、抗纖維抗體等。由於腸道細菌是致病的關鍵原因之一以及動物研究證實NAFLD 嚴重度與血液中的內毒素及肝臟鐸類受體TLR-4 的表現增高有關，補充益生菌不但可降低這兩項指標，還能改善脂肪肝的病變。然而還需繼續深入研究，這些新的方法是否能真正有效的改善脂肪肝病變。

並列關鍵字

非酒精性脂肪肝病 ； 脂肪性肝炎 ； 病因 ； 治療