EFFICACY AND SAFETY OF ILEAL BILE ACID TRANSPORTER INHIBITORS IN ADULTS WITH AUTOIMMUNE CHOLESTATIC LIVER CONDITIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2025-09-01 DOI:10.1016/j.aohep.2025.101996

Igor Silveira Boechat , Rodolfo Augusto Rezende Assis , Carlos Alberto Leitão Neto Monteiro , Yohanna Idsabella Rossi , Marina Leite de Assis Bezerra Cavalcanti , Guilherme Grossi Lopes Cançado

{"title":"EFFICACY AND SAFETY OF ILEAL BILE ACID TRANSPORTER INHIBITORS IN ADULTS WITH AUTOIMMUNE CHOLESTATIC LIVER CONDITIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS","authors":"Igor Silveira Boechat , Rodolfo Augusto Rezende Assis , Carlos Alberto Leitão Neto Monteiro , Yohanna Idsabella Rossi , Marina Leite de Assis Bezerra Cavalcanti , Guilherme Grossi Lopes Cançado","doi":"10.1016/j.aohep.2025.101996","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Autoimmune cholestatic liver diseases (ACLD), including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), involve chronic bile duct injury and impaired bile flow, reducing quality and expectancy of life. Pruritus affects 20–70% of patients and is often resistant to treatment. Ileal bile acid transporter (IBAT) inhibitors, which reduce intestinal bile acid reabsorption, have emerged as a promising option for relieving cholestatic itch. This systematic review and meta-analysis evaluated the efficacy and safety of IBAT inhibitors in adults with ACLD.</div></div><div><h3>Materials and Methods</h3><div>A systematic review was conducted according to PRISMA guidelines using PubMed, Embase, and Cochrane-CENTRAL. Included studies enrolled adults with ACLD and pruritus lasting ≥12 weeks, treated with IBAT inhibitors. The primary outcome was change in pruritus severity (5-D Itch Scale). Secondary outcomes included sleep disturbance, serum bile acids, hepatic enzymes, and adverse events. Heterogeneity was assessed with I<sup>2</sup> and Cochrane Q tests.</div></div><div><h3>Results</h3><div>Three studies (n = 180)—two randomized controlled trials and one non-randomized study—met inclusion criteria. Most patients were female (78%), diagnosed with PBC (85%), and treated with linerixibat (77%). IBAT inhibitors significantly reduced pruritus scores (mean difference: -4.93; 95% CI: -6.26 to -3.59; p < 0.0001) and improved sleep quality (mean difference: -8.12; 95% CI: -13.54 to -2.70; p = 0.0033). Biochemical changes included decreased serum bile acids, autotaxin, and FGF19, and increased C4. AST and GGT levels declined, while ALT and bilirubin remained stable. Adverse events occurred in 89.7% of participants, mainly diarrhea (22.7%), abdominal pain (18.2%), and nausea (12.2%). Serious adverse events were rare (2.2%).</div></div><div><h3>Conclusions</h3><div>IBAT inhibitors significantly improved pruritus and sleep in adults with ACLD, with an acceptable safety profile. These findings support their potential as a novel treatment for cholestatic pruritus.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 ","pages":"Article 101996"},"PeriodicalIF":4.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of hepatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1665268125002212","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction and Objectives

Autoimmune cholestatic liver diseases (ACLD), including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), involve chronic bile duct injury and impaired bile flow, reducing quality and expectancy of life. Pruritus affects 20–70% of patients and is often resistant to treatment. Ileal bile acid transporter (IBAT) inhibitors, which reduce intestinal bile acid reabsorption, have emerged as a promising option for relieving cholestatic itch. This systematic review and meta-analysis evaluated the efficacy and safety of IBAT inhibitors in adults with ACLD.

Materials and Methods

A systematic review was conducted according to PRISMA guidelines using PubMed, Embase, and Cochrane-CENTRAL. Included studies enrolled adults with ACLD and pruritus lasting ≥12 weeks, treated with IBAT inhibitors. The primary outcome was change in pruritus severity (5-D Itch Scale). Secondary outcomes included sleep disturbance, serum bile acids, hepatic enzymes, and adverse events. Heterogeneity was assessed with I² and Cochrane Q tests.

Results

Three studies (n = 180)—two randomized controlled trials and one non-randomized study—met inclusion criteria. Most patients were female (78%), diagnosed with PBC (85%), and treated with linerixibat (77%). IBAT inhibitors significantly reduced pruritus scores (mean difference: -4.93; 95% CI: -6.26 to -3.59; p < 0.0001) and improved sleep quality (mean difference: -8.12; 95% CI: -13.54 to -2.70; p = 0.0033). Biochemical changes included decreased serum bile acids, autotaxin, and FGF19, and increased C4. AST and GGT levels declined, while ALT and bilirubin remained stable. Adverse events occurred in 89.7% of participants, mainly diarrhea (22.7%), abdominal pain (18.2%), and nausea (12.2%). Serious adverse events were rare (2.2%).

Conclusions

IBAT inhibitors significantly improved pruritus and sleep in adults with ACLD, with an acceptable safety profile. These findings support their potential as a novel treatment for cholestatic pruritus.

查看原文本刊更多论文

回肠胆汁酸转运蛋白抑制剂治疗自身免疫性胆汁淤积性肝病的有效性和安全性：一项系统综述和荟萃分析

自身免疫性胆汁淤积性肝病（ACLD），包括原发性胆道炎（PBC）和原发性硬化性胆管炎（PSC），涉及慢性胆管损伤和胆汁流动受损，降低生活质量和预期寿命。瘙痒症影响20-70%的患者，并且通常对治疗有抗药性。回肠胆汁酸转运蛋白（IBAT）抑制剂，减少肠道胆汁酸的再吸收，已经成为缓解胆汁淤积性瘙痒的一个有希望的选择。本系统综述和荟萃分析评估了IBAT抑制剂治疗成人ACLD的有效性和安全性。材料和方法根据PRISMA指南，使用PubMed、Embase和Cochrane-CENTRAL进行系统评价。纳入的研究纳入了ACLD和瘙痒持续≥12周的成人，使用IBAT抑制剂治疗。主要观察指标为瘙痒严重程度的改变（5-D瘙痒量表）。次要结局包括睡眠障碍、血清胆汁酸、肝酶和不良事件。采用I2和Cochrane Q检验评估异质性。结果3项研究（n = 180）- 2项随机对照试验和1项非随机研究符合纳入标准。大多数患者为女性（78%），诊断为PBC(85%)，并接受利奈昔巴治疗（77%）。IBAT抑制剂显著降低瘙痒评分（平均差异：-4.93;95% CI: -6.26至-3.59;p < 0.0001）并改善睡眠质量（平均差异：-8.12;95% CI: -13.54至-2.70;p = 0.0033）。生化变化包括血清胆汁酸、自taxin和FGF19降低，C4升高。AST和GGT水平下降，而ALT和胆红素保持稳定。不良事件发生率为89.7%，主要为腹泻（22.7%）、腹痛（18.2%）和恶心（12.2%）。严重不良事件罕见（2.2%）。结论sibat抑制剂可显著改善成人ACLD患者的瘙痒和睡眠，且具有可接受的安全性。这些发现支持了它们作为一种治疗胆汁淤积性瘙痒的新方法的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.