Chronic liver diseases are prevalent, particularly among patients with type 2 diabetes, who have a higher incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and are subject to other liver diseases.1 With no pharmacotherapy for these liver conditions, recent attention was given to glucagon-like peptide-1 receptor agonists (GLP1a) for their effectiveness in treating type 2 diabetes and obesity and in reducing liver enzyme levels and liver fat levels.2 A 72-week, phase II, placebo-controlled randomised trial in patients with non-alcoholic steatohepatitis (NASH) and liver fibrosis found that the GLP1a semaglutide improves the resolution of NASH but does not affect fibrosis regression.2 By its limited size, however, this trial could not provide effectiveness data on major liver outcomes (MALO), such as decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or liver-related death, despite its long-term follow-up. Non-randomised observational studies can be useful to address such questions. In Gut , Wester et al 3 present an observational study that evaluates the effectiveness of GLP1a in the long-term incidence of MALO in patients with chronic liver disease and type 2 diabetes. They use data from Swedish healthcare registers between 2010 and 2020 to identify all Swedish adult residents with diagnoses of chronic liver disease and type 2 diabetes and who filled at least one prescription of metformin, an indication for second-line treatment with a GLP1a (liraglutide, semaglutide, dulaglutide, exenatide and lixisenatide). Within this base cohort, defined as of January 2010, initiation and continuation of a GLP1a were compared with non-initiation. The outcome was the first MALO event to occur during follow-up, namely decompensated cirrhosis (variceal bleeding, ascites, portal hypertension or hepatorenal syndrome), hepatocellular carcinoma, need for liver transplantation or MALO-related death. The authors emulated a hypothetical pragmatic randomised controlled trial (RCT), a so-called ‘target trial’, by generating a series of 131 separate ‘trials’, …

中文翻译：

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胰高血糖素样肽 1 受体激动剂治疗慢性肝病：真实证据还是模糊不清？

慢性肝病很普遍，特别是在 2 型糖尿病患者中，他们代谢功能障碍相关的脂肪肝病 (MASLD) 的发生率较高，并且患有其他肝脏疾病。1 由于这些肝脏疾病尚无药物治疗，最近的关注点是胰高血糖素样肽 1 受体激动剂 (GLP1a) 因其在治疗 2 型糖尿病和肥胖以及降低肝酶水平和肝脂肪水平方面的有效性而被给予。2 一项针对患者的为期 72 周的 II 期安慰剂对照随机试验患有非酒精性脂肪性肝炎 (NASH) 和肝纤维化的研究发现，GLP1a 索马鲁肽可改善 NASH 的消退，但不会影响纤维化消退。2 然而，由于规模有限，该试验无法提供主要肝脏结局 (MALO) 的有效性数据，如失代偿性肝硬化、肝细胞癌、肝移植或肝相关死亡，尽管有长期随访。非随机观察研究有助于解决此类问题。在 Gut 中，Wester 等人 3 提出了一项观察性研究，评估 GLP1a 对慢性肝病和 2 型糖尿病患者 MALO 长期发病率的有效性。他们使用 2010 年至 2020 年间瑞典医疗保健登记册的数据来识别所有被诊断患有慢性肝病和 2 型糖尿病并至少开过一张二甲双胍处方的瑞典成年居民，二甲双胍是 GLP1a（利拉鲁肽、利拉鲁肽、索马鲁肽、度拉鲁肽、艾塞那肽和利西拉肽）。在这个定义为 2010 年 1 月的基础队列中，GLP1a 的启动和持续与未启动进行了比较。结果是随访期间发生的第一个 MALO 事件，即失代偿性肝硬化（静脉曲张出血、腹水、门静脉高压或肝肾综合征）、肝细胞癌、需要肝移植或 MALO 相关死亡。作者模拟了一项假设的实用随机对照试验 (RCT)，即所谓的“目标试验”，通过生成一系列 131 项独立的“试验”，……