GLP-1受体激动剂和代谢功能障碍相关的脂肪性肝病患者的肝硬化和相关并发症的风险

代谢功能障碍相关的脂肪分裂肝病（MASLD）是肝硬化的越来越多的原因。 Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health行政公司数据仓库和中央癌症注册表。在2006年1月1日至2022年6月30日之间，在130名退伍军人卫生管理局医院和相关的卧床诊所中看到的MASLD和糖尿病患者，他们在2006年1月1日至2022年6月30日之间启动了GLP-1 RA或二肽基肽酶4抑制剂（DPP-4I）的患者。从基线到研究结果之一或研究期结束（2022年12月31日）的患者进行跟踪，以先到者为准。每个glp-1 ra新用户的倾向分数与同一个月启动A DPP-4I的患者的比例为1：1。 Separate analyses were conducted among patients without and with cirrhosis at baseline.For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality.对于肝硬化的患者，主要结果是肝硬化并发症的复合结果，第二结局是启动GLP-1 RAS的16058例患者，14606年的16058例患者是cirrhosis（平均[SD]年龄，60.56 [10.31]年度； 15.31515.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.89.15。肝硬化（平均[SD]年龄，66.99 [7.09]年； 1360 [93.7％]男性）。这些患者与启动DPP-4I的患者数量相等。在没有肝硬化的患者中，与使用DPP-4I相比，使用GLP-1 RA的患者与肝硬化的风险较低有关（9.98 vs 11.10人为每1000人年；危险比[HR]，0.86; 95％CI，0.75-0.98）。对于次级结果也可以看到类似的结果。与使用DPP-4I相比，使用GLP-1 RA的使用与肝硬化并发症复合结果的风险较低有关（1.89 vs 2.55个每1000人年的事件； HR，0.78; HR，0.78; 95％CI，0.59-1.04）和死亡率（21.77 vs 24.43 vs 24.43 vs每1000个人年度; hr，0.00. HR，0.85％; 95％; 95％; 95％; 95％; 95％; 95％，95％，95％，95％，95％c。在肝硬化患者中，GLP-1 RA的使用与结局之间没有关联。在这项研究研究中，GLP-1 RA的使用与MASLD和糖尿病患者的肝硬化和死亡率的较低风险有关。在现有肝硬化的患者中没有看到保护性关联，强调了疾病病程中治疗的重要性。

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first.Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline.For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality.Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis.In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course.