Musso Giovanni, Pinach Silvia, Mariano Filippo, Saba Francesca, De Michieli Franco, Framarin Luciana, Berrutti Mara, Paschetta Elena, Parente Renato, Lizet Castillo Yanina, Leone Nicola, Castellino Francesca, Cassader Maurizio, Gambino Roberto
MECAU Department, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy.
Hepatology. 2025 Feb 1;81(2):560-575. doi: 10.1097/HEP.0000000000000937. Epub 2024 May 28.
NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH.
In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73 m 2 /y, p = 0.009), fasting glucose(-17 mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39 mg/dL; 95% CI = -45, -33), triglycerides (-36 mg/dL, 95% CI = -46, -26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed.
In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.
非酒精性脂肪性肝炎（NASH）会增加肝脏相关疾病及肾脏疾病的发病风险。磷脂姜黄素（Meriva）是一种磷脂制剂，可改善姜黄素的全身吸收与递送。我们评估了Meriva治疗NASH的安全性与疗效。
在这项双盲试验中，5 * 2例经活检证实为NASH的患者（71%为≥F2期纤维化，58%为A2 - G2/A2 - G3a期慢性肾脏病）按1:1随机分组，接受2g/d的Meriva或安慰剂治疗72周。主要终点为NASH缓解且纤维化无恶化。次要终点包括肝纤维化改善≥1期且NASH无恶化；显著（即≥F2期）纤维化和慢性肾脏病的消退；以及肾脏、血糖、血脂和炎症参数的改善。我们还探讨了对肝细胞核因子-κB（NF - κB）激活的治疗效果，NF - κB是一种关键的促炎转录因子，也是姜黄素的主要作用靶点。51例患者（26例接受Meriva治疗，25例接受安慰剂治疗）完成了试验。接受Meriva治疗的16例（62%）患者与接受安慰剂治疗的3例（12%）患者实现了NASH缓解（相对风险[RR]=5.33[95%置信区间（CI）=1.76 - 12.13]；p = 0.003）。接受Meriva治疗的13例（50%）患者与接受安慰剂治疗的2例（8%）患者肝纤维化改善≥1期（RR = 6.50[1.63 - 21.20]；p = 0.008）。接受Meriva治疗的11例（42%）患者与接受安慰剂治疗的0例（0%）患者显著肝纤维化消退（RR = 18.01[1.43 - 36.07]；p = 0.02）。肝脏NF - κB抑制可预测NASH缓解（曲线下面积[AUC]=0.90，95%CI = 0.84 - 0.95）和纤维化改善（AUC = 0.89，95%CI = 0.82 - 0.96）。接受Meriva治疗的13例（50%）患者与接受安慰剂治疗的0例（0%）患者慢性肾脏病消退（RR = 10.71[1.94 - 17.99]；p = 0.004）。与安慰剂相比，Meriva改善了估算肾小球滤过率（eGFR）（调整后的eGFR变化差值：+3.59[2.96 - 4.11]mL/min/1.73m²/y，p = 0.009）、空腹血糖（-17mg/dL；95%CI = -22，-12）、糖化血红蛋白（-0.62%；95%CI = -0.87%，-0.37%）、低密度脂蛋白胆固醇（LDL - C）（-39mg/dL；95%CI = -45，-33）、甘油三酯（-36mg/dL，95%CI = -46，-26）、高密度脂蛋白胆固醇（HDL - C）（+10mg/dL；95%CI = +8，+11）以及炎症标志物。不良事件罕见、轻微且分布均匀。
在NASH患者中，给予Meriva治疗72周是安全的，耐受性良好，并且可能通过抑制NF - κB改善了肝脏组织学、肾脏疾病和代谢指标。
