Shah Raj A, Kowdley Kris V
Liver Institute Northwest , Seattle, WA, USA.
Expert Rev Gastroenterol Hepatol. 2020 May;14(5):311-321. doi: 10.1080/17474124.2020.1748498. Epub 2020 May 12.
NAFLD has grown to become the most prevalent liver disease in the world, with a quarter of the general population estimated to have the disease. NASH, characterized as NAFLD with inflammation, is associated with worsening fibrosis along with increased incidence of HCC. Despite high prevalence of this disease, no pharmacologic treatments approved by regulatory agencies are available.
This review briefly discusses present understanding of NASH pathology and currently available treatments. We also discuss data on the role of OCA as an FXR agonist in modulating disease in NASH. A comprehensive literature search of review articles, original research articles, and prospective clinical trials from 1998 to the present was performed.
Based on 18-month interim findings of the REGENERATE trial, OCA likely improves fibrosis in NASH and therefore may have a beneficial effect in delaying or even preventing cirrhosis. The side effect of an atherogenic lipoprotein profile may adversely affect long-term outcomes, though studies have shown that co-administration of statins is able to mitigate this effect. OCA is likely to become an option for treatment, but the specific context within which it may be prescribed still needs to be clarified.
非酒精性脂肪性肝病（NAFLD）已发展成为全球最普遍的肝脏疾病，估计有四分之一的普通人群患有该疾病。非酒精性脂肪性肝炎（NASH）的特征是伴有炎症的NAFLD，与肝纤维化加重以及肝细胞癌（HCC）发病率增加相关。尽管该疾病患病率很高，但尚无监管机构批准的药物治疗方法。
本综述简要讨论了目前对NASH病理学的认识以及当前可用的治疗方法。我们还讨论了奥贝胆酸（OCA）作为法尼醇X受体（FXR）激动剂在调节NASH疾病中的作用的数据。对1998年至今的综述文章、原始研究文章和前瞻性临床试验进行了全面的文献检索。
根据REGENERATE试验18个月的中期结果，OCA可能改善NASH中的纤维化，因此可能对延缓甚至预防肝硬化有有益作用。致动脉粥样硬化脂蛋白谱的副作用可能对长期结果产生不利影响，不过研究表明，联合使用他汀类药物能够减轻这种影响。OCA可能会成为一种治疗选择，但仍需明确其可能的具体处方背景。
