代谢功能障碍相关的脂肪肝病 (MASLD) 是导致肝硬化的一个日益重要的原因。胰高血糖素样肽 1 受体激动剂 (GLP-1 RA) 可有效改善 MASLD 患者的肝脏炎症。确定使用 GLP-1 RA 是否与降低发生肝硬化及其并发症（包括失代偿和肝细胞癌）的风险相关（HCC），在 MASLD 患者中。这项回顾性队列研究采用主动比较器、新用户设计，使用来自国家退伍军人健康管理局企业数据仓库和中央癌症登记处的数据。 2006 年 1 月 1 日至 2022 年 6 月 30 日期间在 130 家退伍军人健康管理局医院和相关门诊诊所就诊并开始使用 GLP-1 RA 或二肽基肽酶 4 抑制剂 (DPP-4i) 的 MASLD 和糖尿病患者，包括。从基线开始对患者进行随访，直至其中一项研究结果或研究期结束（2022 年 12 月 31 日），以先到者为准。每个 GLP-1 RA 新用户的倾向评分与接受治疗的患者按 1:1 的比例匹配。同月启动了 DPP-4i。对基线时无肝硬化和患有肝硬化的患者进行单独分析。对于无肝硬化的患者，主要结局是进展为肝硬化，由经过验证的诊断代码或肝纤维化的非侵入性标志物定义，次要结局是肝硬化并发症，定义为复合和肝硬化并发症。个体并发症，包括失代偿、肝癌或肝移植以及全因死亡率。对于肝硬化患者，主要结局是肝硬化并发症的复合结局，次要结局是失代偿、HCC 和全因死亡率。 在开始 GLP-1 RA 的 16058 名患者中，14606 名没有肝硬化（平均 [基线时，13015 名 [SD] 年龄，60.56 [10.31] 岁；13015 名 [89.1%] 男性），1452 名患有肝硬化（平均 [SD] 年龄，66.99 [7.09] 岁；1360 名 [93.7%] 男性）。这些患者与启动 DPP-4i 的相同数量的患者相匹配。在无肝硬化的患者中，与使用 DPP-4i 相比，使用 GLP-1 RA 与较低的肝硬化风险相关（每 1000 人年 9.98 次事件 vs 11.10 次事件；风险比 [HR]，0.86；95% CI，0.75 -0.98）。次要结果也出现了类似的结果。与使用 DPP-4i 相比，使用 GLP-1 RA 与较低的肝硬化并发症综合结局风险相关（每 1000 人年 1.89 例 vs 2.55 例事件；HR，0.78；95% CI，0.59-1.04）死亡率（每 1000 人年 21.77 例 vs 24.43 例事件；HR，0.89；95% CI，0.81-0.98）。 GLP-1 RA 的使用与肝硬化患者的结局之间没有关联。在这项队列研究中，GLP-1 RA 的使用与 MASLD 和糖尿病患者进展为肝硬化和死亡率的较低风险相关。在患有肝硬化的患者中没有发现这种保护性关联，这强调了在病程早期进行治疗的重要性。

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.