评价原发性胆管炎患者对二线治疗的反应和对udca反应不足：肝活检随访的初步研究

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2025-09-01 DOI:10.1016/j.aohep.2025.101989

Alejandra Villamil , Daniela de la Viña , Eduardo Mullen , Ignacio Lucero , Juan Carlos Bandi

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引用次数: 0

摘要

对二线治疗的反应是改善胆汁淤积参数和预防纤维化或肝脏事件。目的：评估第12个月的反应，并确定与反应相关的流行病学、临床和组织学结果。患者和方法50例开始OCA (n=12)， PPAR激动剂（n=29）或两者联合（n=9）的患者完成了12个月的治疗，并进行了基线和M12活检。用细胞角蛋白7和19和Scheuer分期评估导管损失。记录胆道界面活动及胆管损伤情况。在基线和12个月时进行弹性成像。采用参数t检验和单因素方差分析进行统计分析。结果平均年龄53.6±10.6岁，女性占84%。平均ALP 388.8±166.6,ALT 71.3±40.6,BT 0.9±0.4。肝硬化10例。二线治疗对POISE标准的应答率为30% (n=15)，对ALP正常化的应答率为14% （n=7）。男性（p.04）、中度/重度ductopia （p.01）、ALT升高（82 vs 46, p.003）、胆红素（1.07 vs 0.7, p.02）和肝硬化（p.02）与无应答相关。在28个样本中观察到中度/重度门静脉炎症伴界面肝炎和小叶溢出，与年龄无关，并与纤维化相关。严重炎症患者无应答（n=5），中度炎症患者仅有21%应答（n=5）。在FU活检中，11例患者的反应与炎症改善有关。轻度ductopia不影响反应。LFT不能预测肝硬化或门静脉炎症。12个月肝硬化与5例肝脏事件相关，导致1例肝脏相关死亡和3例肝脏移植。弹性成像与肝硬化和肝脏事件相关（10.4 vs 22.9, p<0.001），但与炎症或ductoloia无关。结论snon应答（70%）与男性、肝硬化、转氨酶、中重度炎症和ductopia有关。肝硬化和弹性成像与肝脏事件相关。不良组织学结果提示早期二线干预。

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EVALUATION OF RESPONSE TO SECOND LINE THERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE TO UDCA: A PILOT STUDY OF LIVER BIOPSIES FOLLOW UP

Introduction and Objectives

Response to second line therapy is improvement of cholestatic parameters and prevention of fibrosis or liver events. AIM: to evaluate response at Month 12 and identify epidemiological, clinical and histological findings related to response.

Patients and Methods

50 patients initiating OCA (n=12), PPAR agonists (n=29) or combination of both (n=9) completed 12 months treatment and had baseline and M12 biopsy. Duct loss was evaluated with cytokeratin 7 and 19 and Scheuer staging applied. Biliary interface activity and bile duct damage recorded. Elastography was done at baseline and at 12 months. Statistical analysis using parametric t tests and 1-way ANOVA was performed.

Results

Mean age 53.6±10.6y and 84 % female. Mean ALP 388.8±166.6, ALT 71.3±40.6 and BT 0.9±0.4. 10 patients were cirrhotic. Response to second line therapy was 30 % with POISE criteria (n=15) and 14 % for ALP normalization (n=7). Male sex (p.04), moderate/severe ductopenia (p.01), elevated ALT (82 vs 46, p.003), bilirubin (1.07 vs 0.7, p.02) and cirrhosis (p.02) correlated with no response. Moderate/severe portal inflammation with interface hepatitis and lobular spilling was observed in 28 samples, irrespective of age and correlated with fibrosis. No patient with severe inflammation achieved response (n=5), and only 21% with moderate inflammation (n=5). On FU biopsies, response related with improvement of inflammation in 11 patients. Mild ductopenia did not affect response. No LFT predicted cirrhosis or portal inflammation. Cirrhosis at month 12 correlated with liver events in 5 patients resulting in 1 liver related death and 3 transplants. Elastography correlated with cirrhosis and liver events (10.4 vs 22.9, p<0.001) but not with inflammation or ductopenia.

Conclusions

Non response (70 %) related to male sex, cirrhosis, transaminases, moderate/severe inflammation and ductopenia. Cirrhosis and elastography correlated with liver events. Adverse histological findings suggest early second line intervention.

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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.