Partho Pratik Roy, Mamun Al Mahtab, Mohammad Abdur Rahim, Sm Sabrina Yesmin, Sunan Bin Islam, Sheikh Mohammad Fazle Akbar
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However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. The safety profile of different doses of OCA needs to be established in these patients as well as there remain considerable queries about these.</p><p><strong>How to cite this article: </strong>Roy PP, Mahtab MA, Rahim MA, <i>et al</i>. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. 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It appears that considerable numbers of the general population have been suffering from NAFLD. When a patient with NAFLD also exhibits inflammation of the liver, the condition is regarded as nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a pathological entity that may progress to cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). It is acceptable by all that the health burden of NAFLD and NASH is tremendous. Due to the increased prevalence of these pathologies, extensive research has been conducted regarding pathogenesis, diagnostic tools, and staging of the diseases. However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. 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引用次数: 3
摘要
非酒精性脂肪性肝病(NAFLD)是国内外主要的流行肝病之一。一般人群中似乎有相当数量的人患有NAFLD。当NAFLD患者同时表现出肝脏炎症时,这种情况被认为是非酒精性脂肪性肝炎(NASH)。非酒精性脂肪性肝炎是一种可能发展为肝硬化(LC)和肝细胞癌(HCC)的病理实体。NAFLD和NASH的健康负担是巨大的,这是所有人都可以接受的。由于这些病理的患病率增加,已经进行了广泛的研究,关于发病机制,诊断工具和疾病的分期。然而,对这些病理缺乏充分和批准的药物治疗。法内甾体受体(FXR)是一种胆汁酸激活受体。它调节脂质,葡萄糖,胆汁酸代谢。法内脂受体在肝脏上也具有抗炎和抗纤维化的特性。奥贝胆酸(OCA)是一种有效的选择性FXR配体,可能成为对抗NASH和晚期纤维化的有前途的分子。本综述简要讨论了目前推荐的NASH治疗方法和现有的药物治疗方法。讨论了OCA的范围,重点是近期主要随机对照试验(rct)的数据。根据目前的数据和最近的中期分析,OCA似乎可以改善NASH患者的胰岛素抵抗、脂肪性肝炎、丙氨酸转氨酶(ALT)水平和纤维化。与剂量相关的副作用如瘙痒和血脂异常可能限制其使用。此外,它在NASH肝硬化患者中的使用可能受到限制。需要更充分的随机对照试验来纳入具有不同和异质性特征的NASH患者,以形成对这些问题的共识。不同剂量OCA的安全性需要在这些患者中确定,并且对此仍有相当多的疑问。如何引用本文:Roy PP, Mahtab MA, Rahim MA等。奥贝胆酸治疗非酒精性脂肪性肝炎的现状中华肝病与胃肠病杂志,2010;12(增刊1):446 - 450。
Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status.
Nonalcoholic fatty liver disease (NAFLD) is one of the major and prevalent liver diseases from the national and global perspectives. It appears that considerable numbers of the general population have been suffering from NAFLD. When a patient with NAFLD also exhibits inflammation of the liver, the condition is regarded as nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a pathological entity that may progress to cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). It is acceptable by all that the health burden of NAFLD and NASH is tremendous. Due to the increased prevalence of these pathologies, extensive research has been conducted regarding pathogenesis, diagnostic tools, and staging of the diseases. However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. The safety profile of different doses of OCA needs to be established in these patients as well as there remain considerable queries about these.
How to cite this article: Roy PP, Mahtab MA, Rahim MA, et al. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S46-S50.