udca - bezafbrate联合治疗treatment-naÏve原发性胆管炎早期alp正常化率高：初步结果

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2025-09-01 DOI:10.1016/j.aohep.2025.102033

Juan Antonio Sorda , Fernando Javier Barreyro , Matías Bori , Guillermo Fernández , Esteban González Ballerga

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引用次数: 0

摘要

介绍和目的 6个月碱性磷酸酶（ALP）正常化可预测原发性胆管炎（PBC）患者1年的疗效和生存率。贝扎菲特（BZF）有利于不完全熊去氧胆酸（UDCA）应答者。因此，我们评估了单独UDCA与两种不同剂量UDCA+BZF在6个月时的ALP正常化。材料和技术的一个开放性试验(2022年1月 - 2025)antimitochondrial-antibody-positive non-cirrhotic PBC患者随机2 : 2 : 1 UDCA 13 - 15  毫克公斤⁻ 天⁻1 (n = 21), UDCA + BZF 400 毫克(n = 23)或UDCA + BZF 800 毫克(n = 8)。6个月内每月进行肝脏检查。主要终点为ALP ≤ 1 × 在 6月的ULN；次要终点是其他酶的变化、瘙痒和安全性。结果 52例(94 %女,57 ±  11年,BMI 25 ± 6 公斤 m⁻2,组织学阶段1 (n23) / 2 (n16/3 (n13)跟进完成。78年36与UDCA %,高山正常化 % UDCA + BZF  400毫克和100 % UDCA + BZF 800 毫克(χ2 & lt; 0.01)。6个月时的平均ALP （× ULN）为1.5±0.7 (UDCA), 0.98±0.2 （UDCA+BZF 400 mg）和0.8±0.2 (UDCA+BZF 800 mg) （ANOVA p<0.001）。线性混合效应分析显示，所有组的ALP均随时间显著下降；BZF增强了这些月斜率（β = ，400 mg时-0.34,800 mg时-0.44，与UDCA相比，均为Tukey-adjusted p<；0.01）。14 %的UDCA受体持续瘙痒，但BZF组没有瘙痒，两组之间肾功能和肌酸激酶没有变化。结论sup -front UDCA+BZF实现了剂量依赖性、接近普遍的6个月ALP正常化，加速了生化改善，无早期安全性问题。这些临时数据支持在诊断时开始联合治疗，特别是对有症状的PBC。

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HIGH RATE OF EARLY ALP NORMALIZATION WITH UDCA–BEZAFIBRATE COMBINATION THERAPY IN TREATMENT-NAÏVE PRIMARY BILIARY CHOLANGITIS: PRELIMINARY RESULTS

Introduction and Objectives

 Six-month alkaline phosphatase (ALP) normalisation predicts one-year response and survival in primary biliary cholangitis (PBC). Bezafibrate (BZF) benefits incomplete ursodeoxycholic-acid (UDCA) responders. We therefore assessed ALP normalization at six-month with UDCA alone versus UDCA+BZF at two different doses.

Materials and Methods

in an open-label trial (January 2022–2025) antimitochondrial-antibody–positive, non-cirrhotic PBC patients were randomised 2 : 2 : 1 to UDCA 13–15 mg kg⁻¹ day⁻¹ (n=21), UDCA+BZF 400 mg (n=23) or UDCA+BZF 800 mg (n=8). Liver tests were obtained monthly for six months. The primary end point was ALP ≤ 1 × ULN at month 6; secondary end points were changes in other enzymes, pruritus and safety.

Results

 Fifty-two patients (94 % female, 57 ± 11 years, BMI 25 ± 6 kg m⁻², histological stages 1(n23)/2(n16/3(n13) completed follow-up. ALP normalised in 36 % with UDCA, 78 % with UDCA+BZF 400 mg and 100 % with UDCA+BZF 800 mg (χ² < 0.01). Mean ALP (× ULN) at six months was 1.5±0.7 (UDCA), 0.98±0.2 (UDCA+BZF 400 mg), and 0.8±0.2 (UDCA+BZF 800 mg) (ANOVA p<0.001). Linear mixed-effects analysis showed significant time-dependent ALP declines in all groups; BZF intensified these monthly slopes (β = –0.34 for 400 mg, –0.44 for 800 mg vs UDCA, both Tukey-adjusted p<0.01). Pruritus persisted in 14 % of UDCA recipients but in none on BZF, and renal function and creatine kinase were unchanged across groups.

Conclusions

Up-front UDCA+BZF achieves dose-dependent, near-universal six-month ALP normalisation and accelerates biochemical improvement without early safety concerns. These interim data support initiating combination therapy at diagnosis, particularly in symptomatic PBC.

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来源期刊

Annals of hepatology 医学-胃肠肝病学

CiteScore

7.90

自引率

2.60%

发文量

183

审稿时长

4-8 weeks

期刊介绍： Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.