Data Sheet 4_Sodium-glucose cotransporter-2 inhibitor therapy improves renal and hepatic function in patients with cirrhosis secondary to metabolic dysfunction associated steatotic liver disease and type 2 diabetes.pdf

PurposeMetabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of chronic kidney disease (CKD), compounding morbidity in patients with cirrhosis. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are disease-modifying agents in type 2 diabetes mellitus (T2DM) and CKD, but studies on their use in cirrhosis are limited. We aimed to assess the effect of SGLT2i therapy on renal and hepatic function in patients with Child-Turcotte-Pugh (CTP) B cirrhosis and T2DM.
MethodsWe conducted a 48-month longitudinal, retrospective cohort study of 54 patients with CTP B cirrhosis secondary to MASLD and T2DM who were initiated on SGLT2i (n=27) or insulin (n=27). Laboratory data were collected every 3 months. Liver stiffness (LS) was measured every 6 months via transient elastography (TE) and acoustic radiation force impulse with shear wave velocity (ARFI-SWV). The primary outcome was change in glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage. Secondary outcomes included LS changes measured via TE and ARFI. Additional end points included MELD-Na, MELD 3.0, CTP scores, hepatic decompensations, proteinuria, body mass index (BMI), hemoglobin A1c (Hb-A1c), blood glucose (BG).
ResultsAt baseline, the two groups were comparable in GFR (SGLT2i: 55.6 ± 1.9 vs. insulin: 58.1 ± 2.1 mL/min/1.73 m², p = 0.37), CKD stage, ARFI-SWV (2.9 ± 0.1 vs. 2.8 ± 0.1 m/s, p = 0.26), MELD-Na, and MELD 3.0. The SGLT2i group was older (p < 0.01) and had higher AST (p=0.01), ALT (p<0.01), and CTP scores (p=0.02), but lower LS by TE (p = 0.03). Over 48 months, GFR increased in the SGLT2i group (+13.5 ± 1.3) and declined in the insulin group (−4.2 ± 1.4; p < 0.01). A greater proportion of SGLT2i patients transitioned from CKD stage 3a to 2 (p = 0.04). Liver stiffness by TE decreased in the SGLT2i group (−4.0 ± 1.1 kPa), while it increased in the insulin group (+3.0 ± 2.5 kPa; p < 0.01). ARFI-SWV also declined in the SGLT2i group but increased in the insulin group (2.5 ± 0.1 vs. 3.2 ± 0.1 m/s; p < 0.01). The SGLT2i group also demonstrated significant improvement in MELD-Na, MELD 3.0 and CTP scores, with greater resolution of hepatic decompensations, proteinuria, as well as better BMI and HbA1c outcomes (all p < 0.01).
ConclusionsPatients with CTP B cirrhosis and T2DM receiving SGLT2i therapy experienced a significant improvement in renal, hepatic function, and glycemic control over 48 months compared to patients treated with insulin.

### 研究背景与目的
代谢功能障碍相关脂肪性肝病（Metabolic dysfunction-associated steatotic liver disease, MASLD）会增加慢性肾脏病（chronic kidney disease, CKD）的发病风险，进而加重肝硬化患者的疾病负担与并发症发生风险。钠-葡萄糖协同转运蛋白2抑制剂（Sodium-glucose cotransporter-2 inhibitors, SGLT2i）是2型糖尿病（type 2 diabetes mellitus, T2DM）与慢性肾脏病的疾病修饰治疗药物，但针对其在肝硬化人群中应用的相关研究较为有限。本研究旨在评估钠-葡萄糖协同转运蛋白2抑制剂治疗对Child-Turcotte-Pugh（CTP）分级B级肝硬化合并2型糖尿病患者的肾功能与肝功能的影响。

### 研究方法
本研究为一项为期48个月的纵向回顾性队列研究，纳入54例因代谢功能障碍相关脂肪性肝病并发2型糖尿病且起始接受钠-葡萄糖协同转运蛋白2抑制剂（n=27）或胰岛素（n=27）治疗的Child-Turcotte-Pugh分级B级肝硬化患者。每3个月收集一次实验室检测数据，每6个月通过瞬时弹性成像（transient elastography, TE）以及声辐射力脉冲弹性成像联合剪切波速度（acoustic radiation force impulse with shear wave velocity, ARFI-SWV）检测肝脏硬度（liver stiffness, LS）。本研究的主要结局指标为肾小球滤过率（glomerular filtration rate, GFR）与慢性肾脏病分期的变化；次要结局指标为通过瞬时弹性成像与声辐射力脉冲弹性成像检测得到的肝脏硬度变化。额外研究终点包括终末期肝病模型联合血清钠评分（MELD-Na）、MELD 3.0评分、Child-Turcotte-Pugh评分、肝性失代偿事件、蛋白尿、体质量指数（body mass index, BMI）、糖化血红蛋白（hemoglobin A1c, Hb-A1c）以及血糖（blood glucose, BG）。

### 研究结果
基线时，两组患者的肾小球滤过率[钠-葡萄糖协同转运蛋白2抑制剂组：55.6±1.9 vs 胰岛素组：58.1±2.1 mL/min/1.73m²，p=0.37]、慢性肾脏病分期、声辐射力脉冲弹性成像联合剪切波速度[钠-葡萄糖协同转运蛋白2抑制剂组：2.9±0.1 vs 胰岛素组：2.8±0.1 m/s，p=0.26]、终末期肝病模型联合血清钠评分以及MELD 3.0评分均无显著差异。钠-葡萄糖协同转运蛋白2抑制剂组患者年龄更大（p<0.01），天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）水平以及Child-Turcotte-Pugh评分更高（分别为p=0.01、p<0.01、p=0.02），但瞬时弹性成像检测得到的肝脏硬度更低（p=0.03）。

随访48个月后，钠-葡萄糖协同转运蛋白2抑制剂组患者的肾小球滤过率显著升高（+13.5±1.3），而胰岛素组患者的肾小球滤过率呈下降趋势（-4.2±1.4；p<0.01）。钠-葡萄糖协同转运蛋白2抑制剂组中，更多患者从慢性肾脏病3a期改善至2期（p=0.04）。钠-葡萄糖协同转运蛋白2抑制剂组的瞬时弹性成像检测肝脏硬度值降低（-4.0±1.1 kPa），而胰岛素组则呈升高趋势（+3.0±2.5 kPa；p<0.01）。声辐射力脉冲弹性成像联合剪切波速度检测结果同样显示，钠-葡萄糖协同转运蛋白2抑制剂组出现下降，而胰岛素组出现升高（2.5±0.1 vs 3.2±0.1 m/s；p<0.01）。

此外，钠-葡萄糖协同转运蛋白2抑制剂组患者的终末期肝病模型联合血清钠评分、MELD 3.0评分以及Child-Turcotte-Pugh评分均得到显著改善，肝性失代偿事件、蛋白尿的缓解率更高，体质量指数与糖化血红蛋白控制效果更优（所有指标p<0.01）。

### 研究结论
与接受胰岛素治疗的患者相比，接受钠-葡萄糖协同转运蛋白2抑制剂治疗的Child-Turcotte-Pugh分级B级肝硬化合并2型糖尿病患者，在随访48个月后肾功能、肝功能以及血糖控制情况均得到显著改善。