Ahmed Nabeel R, Kulkarni Vaishnavi Vijaya, Pokhrel Sushil, Akram Hamna, Abdelgadir Arowa, Chatterjee Abanti, Khan Safeera
Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Medicine, Dow International Medical College, Karachi, PAK.
Cureus. 2022 May 8;14(5):e24829. doi: 10.7759/cureus.24829. eCollection 2022 May.
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of developing progressive fibrosis, cirrhosis, and hepatocellular carcinoma. As of now, there are no FDA-approved treatments for NAFLD/non-alcoholic steatohepatitis (NASH) or its associated fibrosis. Although many drugs are under clinical trial, both obeticholic acid (OCA) and semaglutide are among the few that have reached phase III clinical trials, but they were never compared. We decided to conduct a systematic review of randomized controlled trials and meta-analyses. A total of 6,589 articles were found after searching PubMed, OVID Embase, OVID Medline, PubMed Central, and clinicaltrials.gov. Only full-text peer-reviewed articles published in the past six years were put through the Cochrane bias assessment tool or the Assessment of Multiple Systematic Reviews (AMSTAR) tool to screen for bias. After strict quality assessment, data from five randomized controlled trials (n=2,694) and three systematic reviews/meta-analysis (n=8,898) was extracted and included. The data extraction from these studies showed that semaglutide and OCA cause histological improvement, but NASH resolution is exclusive to semaglutide. Although high doses of OCA can cause dyslipidemia and severe pruritus, it is the only therapeutic that causes improvement in NASH-associated hepatic fibrosis. Semaglutide is the safest option among the two and leads to significant weight loss compared to OCA; thus, a better outcome on hepatic steatosis follows. The indications of each of these drugs should be based on the NAFLD activity score and NASH fibrosis stage. OCA should be used with caution among patients with hyperlipidemia and ischemic heart disease as it may make these conditions worst.
非酒精性脂肪性肝病（NAFLD）患者发生进行性纤维化、肝硬化和肝细胞癌的风险增加。目前，美国食品药品监督管理局（FDA）尚未批准用于治疗NAFLD/非酒精性脂肪性肝炎（NASH）或其相关纤维化的药物。尽管许多药物正在进行临床试验，但奥贝胆酸（OCA）和司美格鲁肽是少数进入III期临床试验的药物，但它们从未被比较过。我们决定对随机对照试验和荟萃分析进行系统评价。在检索PubMed、OVID Embase、OVID Medline、PubMed Central和clinicaltrials.gov后，共找到6589篇文章。只有过去六年发表的全文同行评审文章通过Cochrane偏倚评估工具或多重系统评价评估（AMSTAR）工具进行筛选以检测偏倚。经过严格的质量评估，提取并纳入了五项随机对照试验（n = 2694）和三项系统评价/荟萃分析（n = 8898）的数据。这些研究的数据提取表明，司美格鲁肽和OCA可导致组织学改善，但只有司美格鲁肽能使NASH得到缓解。尽管高剂量的OCA可导致血脂异常和严重瘙痒，但它是唯一能改善NASH相关肝纤维化的治疗药物。司美格鲁肽是两者中最安全的选择，与OCA相比可导致显著体重减轻；因此，对肝脂肪变性有更好的疗效。这些药物的适应症应基于NAFLD活动评分和NASH纤维化分期。高脂血症和缺血性心脏病患者应谨慎使用OCA，因为它可能会使这些病情恶化。
