非酒精性脂肪肝病之藥物治療

Pharmacological Interventions of Non-Alcoholic Fatty Liver Disease

肝臟疾患之中，除了廣被人知的病毒性肝炎、肝硬化、肝細胞癌以外，近年來逐漸受到醫學界重視的問題則是非酒精性脂肪肝病（nonalcoholic fatty liver disease, NAFLD）及其相關疾病。非酒精性脂肪性肝炎（nonalcoholic steatohepatitis, NASH）則是NAFLD疾病光譜中最嚴重的疾病進展，常有機會導致肝臟纖維化、肝硬化，甚至肝癌。是以對於NASH的治療是臨床上重要的課題與挑戰。除了運動、飲食控制、減重等非藥物方式之生活方式調整以外，NASH之有效藥物治療方法目前仍未有定論。許多科學研究證據顯示，胰島素阻抗性（insulin resistance, IR）的調節異常是造成NASH的核心因素。是以回顧NASH之藥物治療方式可以由另一面向提供NASH的致病機轉研究的歷程。這些進行至第一期以上的臨床試驗藥物包括胰島素敏感劑（insulin sensitizer）、腸促胰島素（incretin）相關樂物、抗發炎製劑（anti-inflammatory agents）、肝腸軸循環調節劑（Iiver-gut axis modulators）、抗纖維化製劑（anti-fibrosis agents）等。這些不同作用機制藥物的研發與臨床試驗一方面提供了臨床治療上重要的成果以嘉惠於病患，另一方面也提供了轉譯醫學上對於此代謝性肝臟疾病致病機轉上關鍵的釐清。隨著越來越多的藥物積極發展與跨國合作臨床試驗，相信更有機會早日為NASH患者尋找到改善疾病、延長生命與提升生活品質的藥物。

Non-alcoholic fatty liver disease (NAFLD) recently has been in the spotlight as one of the most common liver disorders besides well-known viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is an extreme form across the spectrum of NAFLD. The metabolic liver disorder may lead to fibrosis, cirrhosis and HCC. Therefore, it is indeed an important issue and a challenge in a clinical setting. No definite and approved drug has been launched so far for therapeutic intervention of NASH. Lifestyle modifications, such as exercise, diet, and weight reduction, remain the major step in current management. Robust evidence demonstrated that insulin resistance (IR) and/or its dysregulation play the pivotal role in the development of NASH. Reviewing the paths towards the therapeutic approach for NASH per se also reflected the study paths for pathogenic mechanisms. Currently, some classes of drugs have stepped into phase 1 or more. They include insulin sensitizer, incretin anlogues, anti-inflammatory agents, liver-gut axis modulators, and anti-fibrosis agents. With multiple agents and/or compounds currently recruited into investigation and clinical trials, it is anticipated that such efforts will provide the important clinical implications. In addition, such efforts will shed a light on the path for elucidation of the pathogenic mechanisms in the prevalent metabolic liver disorder. The eventual approval of pharmacologic agents for NASH will come true and the breakthrough will be much beneficial for our patients in terms of disease control, survival, and quality of life.