Previous Article in Journal
Relationship Between Hepatitis B Viral Load and Laboratory Parameters in HBsAg-Positive Patients: Insights from the Sub-Himalayan Region
Previous Article in Special Issue
Impact of Endoscopic Band Ligation on Gastric Complications Associated with Portal Hypertension
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Gastroenterology Insights
Volume 16
Issue 3
10.3390/gastroent16030030
gastroent-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Ileal Bile Acid Transporter Inhibitors for Adult Patients with Autoimmune Cholestatic Liver Diseases: A Systematic Review and Meta-Analysis

by
Igor Boechat Silveira
1,
Rodolfo Augusto Assis Rezende
2,
Carlos Alberto Monteiro Leitão Neto
3,
Yohanna Idsabella Rossi
4,
Marina de Assis Bezerra Cavalcanti Leite
5 and
Guilherme Grossi Lopes Cançado
6,7,*
1
School of Medicine, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Brazil
2
Dipartimento di Gastroenterologia, IRCCS Istituto Clinico Humanitas, 20089 Milan, Italy
3
Dipartimento di Medicina Molecolare, Università di Pavia, 27100 Pavia, Italy
4
School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050-170, Brazil
5
School of Medicine, Universidade Federal da Paraíba, João Pessoa 58051-900, Brazil
6
Departamento de Gastroenterologia e Hepatologia, Hospital da Polícia Militar de Minas Gerais, Belo Horizonte 30110-013, Brazil
7
Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 110, 2o andar, Belo Horizonte 31130-100, Brazil
*
Author to whom correspondence should be addressed.
Gastroenterol. Insights 2025, 16(3), 30; https://doi.org/10.3390/gastroent16030030 (registering DOI)
Submission received: 14 July 2025 / Revised: 18 August 2025 / Accepted: 20 August 2025 / Published: 25 August 2025
(This article belongs to the Special Issue Advances in the Management of Gastrointestinal and Liver Diseases)
Browse Figures
Versions Notes

Abstract

Background: Autoimmune cholestatic liver diseases (AICLDs), including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are characterized by progressive biliary injury and cholestasis, leading to an impaired quantity/quality of life. Pruritus affects 20–70% of patients and is often refractory to current treatments. Ileal bile acid transporter (IBAT) inhibitors reduce bile acid reabsorption and may alleviate cholestatic pruritus. This systematic review and meta-analysis evaluates their efficacy and safety in adults with AICLD. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane-CENTRAL for studies assessing IBAT inhibitors in adult AICLD patients with pruritus for ≥12 weeks. The primary outcome was the change in the 5-D Pruritus Scale. Secondary outcomes included sleep quality, serum bile acids, liver biochemistry, and safety. Heterogeneity was assessed using Cochrane Q and I2 statistics. Results: Three studies (n = 180) met inclusion criteria, including two RCTs and one single-arm study. Patients (78% female; 85% PBC; 77% linerixibat) showed a significant pruritus reduction (MD = −4.93, 95%CI [−6.26, −3.59], p < 0.0001), accompanied by improved sleep quality (MD = −8.12, 95%CI [−13.54, −2.70], p = 0.0033). Serum bile acids, FGF19, and autotaxin decreased significantly, with increased C4 levels. AST and GGT declined, while ALP, ALT, and bilirubin remained stable. Adverse events occurred in 89.7%, mainly diarrhea (22.7%), nausea (12.2%), and abdominal pain (18.2%); serious events were rare (2.2%). Conclusions: IBAT inhibitors significantly reduce pruritus and improve sleep in AICLD, with a favorable safety profile. These findings support their potential as a novel therapeutic option for cholestatic pruritus in adults with AICLD.

1. Introduction

Autoimmune cholestatic liver diseases (AICLDs), which include primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are chronic and progressive diseases that affect the bile ducts leading to an impairment of the normal bile flow, the excessive accumulation of potentially toxic bile acids, and liver fibrosis [1,2,3]. Although relatively rare, these diseases account for a significant proportion of liver transplantations (8–14%) and liver-related mortality worldwide [4].
The progression of AICLD profoundly impacts patients’ quality of life, with pruritus, fatigue, and abdominal pain being major contributors [5,6,7,8]. Therefore, effective symptom management is essential for comprehensive patient care [9,10]. Notably, pruritus affects 20–70% of patients at some point during the disease evolution, significantly impairing cognitive, emotional, and social well-being, leading to substantial disability, sleep deprivation, and worsening fatigue [10]. Despite its burden, pruritus remains challenging to manage due to an incomplete understanding of its molecular pathogenesis [11]. Current pharmacological options include cholestyramine, peroxisome proliferator-activated receptor (PPAR) agonists, rifampin, naltrexone, and sertraline, while liver transplantation may be considered for refractory, intolerable cases [12,13,14]. PPAR agonists, specifically, are an emerging option for the treatment of pruritus in autoimmune cholestatic liver diseases, with seladelpar and elafibranor showing promising results in PBC [15,16,17,18,19]. However, many patients remain symptomatic despite treatment, highlighting the ongoing clinical need for additional therapeutic options for cholestatic pruritus [12,13].
Ileal bile acid transporter (IBAT) inhibitors, such as maralixibat, odevixibat, and linerixibat, are increasingly prescribed novel therapies for AICLD [20]. By limiting bile acid (BA) reabsorption in the enterohepatic circulation, these agents reduce BA accumulation, a key factor implicated in hepatocyte injury, disease progression, and cholestatic pruritus [21]. Additionally, IBAT inhibitors may help delay the need for more invasive interventions in pruritus management [12]. Previous meta-analyses have demonstrated positive outcomes with IBAT inhibitors in pediatric patients with genetic cholestatic liver diseases [22,23]. However, despite recent studies in adults with PBC and PSC [24,25,26], comprehensive data on their safety and efficacy in AICLD are lacking. This systematic review and meta-analysis aim to critically evaluate and synthesize the currently available evidence on IBAT inhibitors in adults with PBC or PSC, to better understand their therapeutic potential and safety profiles.

2. Materials and Methods

2.1. Protocol Registration

This meta-analysis protocol was registered on PROSPERO with the ID 621722. Our systematic review and meta-analysis were performed and reported in accordance with the Cochrane Collaboration Handbook for Systematic Review of Interventions [27] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [28,29].

2.2. Eligibility Criteria

This meta-analysis included studies that met all of the following eligibility criteria: (1) enrollment of patients over 18 years old, of both sexes, with ongoing pruritus and diagnosed with an AICLD, such as PBC or PSC; (2) inclusion of patients even if on stable doses of ursodeoxycholic acid (UDCA), guideline-supported antipruritic therapies, and antihistamines; (3) use of an IBAT inhibitor regardless of dose or frequency, with at least 12 weeks of follow-up; (4) reporting of at least one outcome of interest; and (5) randomized or observational studies, including pilot studies. Studies with less than 12 weeks of follow-up were excluded, as a preliminary literature review found that shorter follow-up periods resulted in significant heterogeneity compared to studies with longer follow-ups. Additionally, we excluded studies with overlapping populations, case reports, case series, systematic reviews, meta-analyses, liver meeting abstracts, and those that did not report the outcomes of interest.

2.3. Search Strategy and Data Extraction

We systematically searched PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to January 2025. No search filters or language restrictions were applied, and non-English language studies were translated using Google Translate. We also manually searched the references of all included studies, as well as previous systematic reviews and meta-analyses, for any additional relevant studies. Details about the search approach and results are outlined in Supplementary Table S1.
One author (I.S.) deduplicated all identified references, and two independent reviewers (I.S. and C.N.) performed an initial screening based on titles and abstracts. Full-text reviews were conducted for relevant studies. Bibliographic management was conducted using the web application Rayyan [30]. One author (I.S.) extracted data into a spreadsheet covering the following domains: title, journal, year, author, inclusion criteria, IBAT inhibitor and AICLD relative to the study, dose, follow-up time, dose escalation time, total participants, age, gender, mean serum BA at baseline, percentage of patients receiving UDCA, lipid-modifying agents, antihistamines, and outcomes of interest. A second author (C.N.) verified the accuracy of the extracted data.

2.4. Endpoints

Our primary outcome was a change from baseline in the 5-D Pruritus Scale. Secondary outcomes included the following: (1) change from baseline in the Medical Outcomes Study Sleep Scale (MOS-Sleep); (2) efficacy outcomes, including change from baseline in serum bile acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), alkaline phosphatase (ALP), autotaxin (ATX), 7-alpha-hydroxy-4-cholesten-3-one (C4), and fibroblast growth factor 19 (FGF19); and (3) safety outcomes, including any treatment-emergent adverse events (TEAEs), any serious TEAEs, TEAEs leading to drug discontinuation, diarrhea, nausea, and abdominal pain.

2.5. Quality Assessment

Two independent authors (I.S. and R.R.) conducted the quality assessment. The risk of bias in randomized studies was evaluated using version 2 of the Cochrane Risk of Bias assessment tool (RoB 2), while non-randomized studies were assessed using version 2 of the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Any discrepancies were resolved by a third author (G.C.). A traffic light plot of bias assessment was generated for both tools.

2.6. Statistical Analysis

Statistical analysis was performed in R (version 4.4.3). Continuous outcomes were reported as standardized mean changes from baseline with 95% confidence intervals (CIs). When necessary, standard errors (SEs) for continuous outcomes were estimated using methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions [27]. Safety outcomes were analyzed as proportions (event rates), calculated by dividing the number of patients experiencing the adverse event by the total number of patients in the study. When proportions equal to 0 were included, a Freeman–Tukey double arcsine transformation was applied to stabilize variance before pooling. All outcomes were assessed using the DerSimonian and Laird random-effects model, with statistical significance defined as a p-value less than 0.05. Heterogeneity among studies was evaluated using τ2 (tau-squared), the I2 statistic, and Cochran’s Q test p-value. Low heterogeneity was defined as I2 ≤ 25% and a non-significant Q test (p ≥ 0.10). A minimum of two studies was required to generate a forest plot for a specific outcome. The results are presented as forest plots.

3. Results

3.1. Study Selection and Baseline Characteristics

A total of 710 studies were identified, with 296 duplicates manually excluded before screening. After the title and abstract screening, 361 articles were excluded. A full-text assessment was conducted for 53 studies, and 3 articles were ultimately selected for the systematic review and meta-analysis. Our analysis included 180 patients from two randomized controlled trials (RCTs) and one single-arm pilot study. The PRISMA study selection process is in Figure 1.
Among the 180 patients, 69 (38.33%) received maralixibat, while 111 (61.67%) received linerixibat. The majority were female (141, 78%). Most patients (153, 85%) had PBC and were receiving UDCA at the start of the studies, while 27 (15%) had PSC. Follow-up periods ranged from 12 to 14 weeks. Study characteristics are summarized in Table 1, while the main findings are presented in Table 2.

3.2. Design and Inclusion Criteria

Levy et al. (GLIMMER) [24] conducted a randomized, placebo-controlled Phase 2b study to evaluate once- and twice-daily doses of linerixibat in patients with PBC and pruritus. Eligible participants were aged 18–80 years, had moderate-to-severe pruritus (NRS ≥ 4) at the start, and maintained a score of at least three after a 4-week placebo period. The PBC diagnosis was confirmed by sustained elevated ALP levels for at least six months before screening, positive anti-mitochondrial or PBC-specific antinuclear antibodies, or a liver biopsy consistent with PBC. Dose regimen groups comprised six arms: placebo, 20 mg QD (enrollment ceased post-interim analysis), 90 mg QD, 180 mg QD, 40 mg BID (added post-interim analysis), and 90 mg BID.
Mayo et al. [26] conducted a randomized, placebo-controlled study to evaluate the use of once-daily maralixibat in patients with PBC experiencing pruritus. Inclusion criteria included patients aged 18–80 years with significant pruritus, defined as an average daily score > 4.0 on the 10-point Adult Itch Reported Outcome questionnaire for two consecutive weeks. Participants were required to have received UDCA for at least six months or to have a UDCA intolerance. The PBC diagnosis was confirmed according to the American Association for the Study of Liver Diseases guidelines [31]. The study consisted of three groups: one group received a placebo, and the other two received different doses of maralixibat. The dose regimen was divided into two arms: 10 mg QD and 20 mg QD.
Bowlus et al. [25] conducted an open-label Phase 2 study assessing the use of maralixibat in adults with PSC. Patients aged 19 to 80 years were included, regardless of their Itch Reported Outcome score or ALP level. The diagnosis was based on the criteria of the American Association for the Study of Liver Diseases (AASLD) [32]. Patients with inflammatory bowel disease (IBD) were excluded if they had a Mayo Ulcerative Colitis Disease Activity Score of three or higher or if they had experienced an IBD flare recently while using azathioprine. The dose regimen was a maximum of 10 mg QD. At the beginning of the stable dosing period, the mean (SD) dose received was 6.56 mg QD (2.02). This includes the last dose received in participants who discontinued during the dose escalation period.

3.3. Quality Assessment

Mayo et al. [26] were considered to be at a low risk of bias based on the Risk of Bias (RoB 2) tool. In contrast, Levy et al. (GLIMMER) [24] were categorized as having some concerns of bias, primarily due to concerns regarding missing outcome data and the selection of reported results, while other domains were considered to have a low risk of bias. Bowlus et al. [25] were rated as having a serious risk of bias according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I V2) tool. The serious concerns regarding bias were attributed to the confounding and bias in the outcome measurement. Other domains, including bias in the classification of interventions, the selection of participants, deviations from intended interventions, missing data, and the selection of reported results, were assessed as having a low risk of bias. Both quality assessment analyses are described in Supplementary Figures S1 and S2.

3.4. Primary Outcome

IBAT Inhibitors Are Associated with a Significant Improvement of Pruritus

The meta-analysis showed a significant reduction in the 5D-Itch score (MD = −4.93, 95% CI [−6.26, −3.59], p < 0.0001), favoring IBAT inhibitor use, including both maralaxibat and linerixibat. Overall, there was low heterogeneity (τ2 = 1.2204, I2 = 24.6%). The results are presented in Figure 2.

3.5. Secondary Outcomes

3.5.1. Efficacy Outcomes—IBAT Inhibitors Improve Sleep Quality and Reduce Serum Bile Acids, FGF19, and Autotaxin

Two of the three studies reported findings on the mean change from baseline in the MOS Sleep Scale. The meta-analysis showed a significant improvement in sleep quality (MD = −8.12, 95% CI [−13.54, −2.70], p = 0.0033), with no heterogeneity (τ2 = 0, I2 = 0). The results are presented in Figure 3.
All three studies assessed mean differences from baseline in serum BA, FGF19, ATX, and C4. The results indicated a significant reduction in serum BA (MD = −6.81, 95% CI [−9.34, −4.28], p < 0.0001), FGF19 (MD = −51.46, 95% CI [−73.30, −29.61], p < 0.0001), and ATX (MD = −74.41, 95% CI [−118.57, −30.26], p < 0.001). Conversely, there was a significant increase in C4 levels (MD = 25.12, 95% CI [11.84, 38.41], p < 0.0002). Heterogeneity was low for serum BA findings (τ2 = 1.98, I2 = 21.5%) but high for FGF19 (τ2 = 766.50, I2 = 78.2%), ATX (τ2 = 2504.56, I2 = 68.5%), and C4 (τ2 = 345.36, I2 = 93.8%). All results are presented in Supplementary Figure S3.
Two of the three studies also reported changes in serum levels of ALT, AST, GGT, and TB. This meta-analysis revealed significant reductions in AST (MD = −14.74, 95% CI [−24.22, −5.27], p = 0.0023) and GGT (MD = −50.34, 95% CI [−86.48, −14.20], p = 0.0063) levels. However, no significant reductions were observed in ALT (MD = −6.45, 95% CI [−16.43, 3.53], p = 0.2055) or TB (MD = 0.09, 95% CI [−0.03, 0.21], p = 0.15). Heterogeneity was absent for ALT (τ2 = 0, I2 = 0), AST (τ2 = 0, I2 = 0), and GGT (τ2 = 0, I2 = 0), whereas TB levels showed moderate heterogeneity (τ2 = 0.0001, I2 = 40.9%). The results are presented in Figure 4. Two studies also reported changes in serum ALP levels. This meta-analysis showed no significant changes in ALP levels (MD = 8.50, 95% CI [−14.39, 31.39]; p = 0.4666), as presented in Supplementary Figure S4.

3.5.2. Safety Outcomes—Serious Adverse Events Related to IBAT Inhibitors Are Rare and Diarrhea Is the Most Common Adverse Effect

All three studies assessed safety outcomes. The pooled proportion of patients experiencing any adverse event was 89.72% (95% CI [81.90%, 95.76%]), with high heterogeneity (τ2 = 0.0115, I2 = 51.2%). The proportion of patients experiencing serious adverse effects was 2.20% (95% CI [0.00%, 7.18%]), with moderate heterogeneity (τ2 = 0.0105, I2 = 49.0%). Discontinuation due to adverse effects occurred in 8.04% of patients (95% CI [2.39%, 15.89%]), also with moderate heterogeneity (τ2 = 0.0148, I2 = 57.4%). The results are presented in Figure 5.
Among treatment-emergent adverse events (TEAEs), nausea was reported in 12.17% of patients (95% CI [4.89%, 21.61%]), with high heterogeneity (τ2 = 0.0179, I2 = 62.5%). Abdominal pain occurred in 18.17% (95% CI [12.13%, 25.01%]), with low heterogeneity (τ2 = 0.0018, I2 = 9.7%). Diarrhea was observed in 22.70% (95% CI [6.60%, 43.95%]), with very high heterogeneity (τ2 = 0.0869, I2 = 88.2%). The results are presented in Figure 6.

4. Discussion

This study presents a systematic review and meta-analysis of the emerging use of IBAT inhibitors for adult patients with autoimmune cholestatic liver diseases. A total of 180 patients with PBC or PSC across three studies were evaluated. The itch severity, graded by the 5D-Itch score, was significantly reduced by 4.92 points. A significant improvement in sleep quality, as measured by the MOS Sleep Scale, was demonstrated. Furthermore, a significant reduction in serum bile acids, autotaxin, and FGF19 levels was found. AST and GGT levels were reduced, while ALT and bilirubin were not affected after treatment. Although almost 90% of the patients presented a side effect during treatment, the proportion of serious adverse events was very low at 2.2%.
Pruritus is a common and debilitating symptom associated with AICLD and has a profoundly negative impact on the health-related quality of life [33,34]. Cholestatic pruritus is associated with a complex and still not fully understood pathophysiology that seems to affect both peripheral and central nervous systems and involve several mediators like lysophosphatidic acid, autotaxin, bile acids, interleukin 31, and endogenous opioids. IBAT inhibitors are novel drugs that reduce the enterohepatic circulation of bile acids, thereby decreasing their systemic levels [35]. In this meta-analysis we confirm that IBAT inhibitors significantly alleviate cholestatic itching, decreasing both BAs and autotaxin levels. Indeed, a positive relationship between pruritus and elevated serum BAs has been previously shown, and an improvement in pruritus with BA binding resin cholestyramine further supports this hypothesis [15]. In the GLIMMER trial, a ≥30% decrease in total bile acids after linerixibat treatment correlated significantly with a pruritus improvement in PBC [36]. Furthermore, Hegade et al. have demonstrated an association between autotaxin activity, which drives the enzymatic conversion of lysophosphatidylcholine into lysophosphatidic acid, and serum bile acids with PBC pruritus, which are both reduced by IBAT therapy [37].
Treatment with IBAT inhibitors has previously been associated with ALT elevations in pediatric patients with Alagille syndrome [22] and showed no significant differences in AST or ALT levels in genetic cholestasis [23]. In contrast, our meta-analysis found that IBAT inhibitors were associated with a reduction in AST and GGT levels in AICLD, while ALT, bilirubin, and ALP remained unaffected. These findings underscore the importance of investigating this drug class across different cholestatic conditions and patient populations.
Although not part of our meta-analysis, PBC-related pruritus has been assessed using the PBC-40 health-related quality of life instrument [38] in both the GLIMMER and Mayo et al. trials [24,26]. The GLIMMER trial demonstrated significant improvements in the PBC-40’s itch, social, and emotional domains, while the Mayo et al. trial did not find any clinically meaningful improvements. Additionally, a pilot study by Al-Dury et al. also reported improvements on the PBC-40 itch scale [39]. These conflicting results highlight the need for a deeper evaluation of IBAT inhibitors across multiple dimensions of the PBC patient experience. Additional evidence from post hoc and pharmacokinetic–pharmacodynamic analyses of the GLIMMER trial further contextualizes our findings. Tanaka et al. reported consistent therapeutic responses and safety profiles between Japanese and overall trial populations, with the highest itch response rates generally observed in the 40 mg BID group [40]. Von Maltzahn et al. demonstrated a strong correlation between reductions in pruritus severity and improvements in sleep interference, highlighting the broader quality of life benefits of symptom control [41]. Carreno et al. (2023) developed a kinetic–pharmacodynamic model showing a dose-dependent relationship between linerixibat and itch reduction, paralleled by an increased probability of diarrhea, thereby informing the balance between efficacy and tolerability [42]. Carreno et al. (2025) further characterized the dose–C4–diarrhea relationship, emphasizing the importance of selecting doses that optimize pruritus relief while minimizing gastrointestinal side effects [43]. Together, these complementary analyses reinforce the therapeutic potential of IBAT inhibition in PBC, while underscoring the need for individualized dosing strategies and multidomain outcome assessments.
This analysis gathers and summarizes the most recent evidence on IBAT inhibitors in adult patients with AICLD. Multiple clinically relevant parameters related to efficacy, including the pruritus measurement, quality of life scores, and laboratory markers, were assessed. The low heterogeneity in standardized scores suggests a notable consistency in our results. However, this study has several limitations. The small number of included studies restricts the generalizability of our findings. Additionally, the high heterogeneity observed in serum parameters—such as FGF19, ATX, C4, and TB—suggests that multiple factors contribute to the complex pathophysiology of cholestatic pruritus. Variations in disease progression, along with genetic and environmental factors, may affect these biomarkers. The small sample size may have further amplified these variations. Moreover, there was a significant loss of patient data regarding AST, ALT, GGT, TB, and ALP levels. Another limitation is the impact of concomitant IBD. Although IBD is highly prevalent in patients with PSC, this subgroup was underrepresented in our analysis. In the study by Bowlus et al. [25], 27 patients had PSC; however, those with a Mayo Ulcerative Colitis Disease Activity Score of three or higher or a recent IBD flare while using azathioprine were excluded. This limitation reduced our ability to assess the relationship between IBAT inhibitor use and IBD. Given the high incidence of diarrhea in our study population, concerns arise about whether IBAT inhibitors could worsen diarrheal symptoms, contribute to intestinal inflammation, or impair nutrient absorption in patients with IBD. Further studies are needed to explore these potential complications. There was also no standardized dosing regimen across the included studies, and the timing of the dose escalation varied.
The marked differences in the pathophysiology, clinical presentation, and progression between PBC and PSC represent a limitation of our pooled analysis. While IBAT inhibitors have shown promising effects on pruritus in both conditions, the supporting evidence is substantially stronger in PBC [15], where reductions in bile acid levels have been shown to correlate with symptomatic improvement [36]. In PSC, data remain limited, and the impact of concomitant inflammatory bowel disease raises additional safety considerations. Dedicated trials are warranted to clarify the efficacy, safety, and optimal use in PSC. Another important consideration is that none of the included studies reported genetic characteristics of the participants, preventing us from assessing whether genetic variability contributed to differences in the treatment response or disease trajectory.
As an emerging therapy, IBAT inhibitors present challenges in establishing an optimal initial dosing regimen, which remains a key concern for primary studies. Additionally, pruritus is a complex clinical manifestation requiring a multifaceted approach. While various measurement scales and scores exist, our analysis was limited to the available data, allowing us to assess only one of them. Finally, all included studies had relatively short follow-up periods, and longer trials are needed to evaluate the long-term efficacy and safety of IBAT inhibitors.

5. Conclusions

IBAT inhibitors represent a promising therapeutic option for adult patients with AICLD, offering meaningful reductions in pruritus and improvements in sleep, with a generally favorable safety profile. Clinicians may consider their use in appropriately selected patients—particularly those with PBC who have persistent pruritus despite standard therapy—while remaining attentive to gastrointestinal side effects and the potential implications for patients with concomitant IBD.
Future research should focus on longer-term trials to determine sustained efficacy, safety, and optimal dosing strategies across different AICLD subtypes. Studies with larger and more diverse populations are needed to clarify the role of genetic and environmental factors in treatment responses, to establish standardized outcome measures that capture the multidimensional impact of pruritus, and to assess the effects of IBAT inhibitors in specific groups, such as patients with PSC and coexisting IBD. These efforts will be critical to defining the full clinical potential and therapeutic positioning of IBAT inhibition in cholestatic liver disease management.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/gastroent16030030/s1: Figure S1: Summary and graphs of the risk of bias assessment for the included randomized controlled trials. Figure S2: Summary and graphs of the risk of bias assessment for the included observational study. Figure S3: Forest plot illustrating the mean change in serum biochemistry levels: (A) bile acids (BA), (B) fibroblast growth factor 19 (FGF19), (C) autotaxin (ATX), and (D) 7-alpha-hydroxy-4-cholesten-3-one (C4). Figure S4: Forest plot illustrating the mean change in serum alkaline phosphatase (ALP) levels. Table S1: Detailed search strategy, including results and the databases accessed, along with the date of access.

Author Contributions

Conceptualization, I.B.S. and G.G.L.C.; methodology, I.B.S. and G.G.L.C.; validation, I.B.S.; formal analysis, I.B.S.; investigation, I.B.S., R.A.A.R., C.A.M.L.N., Y.I.R. and M.d.A.B.C.L.; data curation, I.B.S.; writing—original draft preparation, I.B.S.; writing—review and editing, G.G.L.C.; supervision, G.G.L.C.; project administration, G.G.L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data is available upon request to the corresponding author.

Conflicts of Interest

GGLC has received a research grant from IPSEN. The other authors have no conflicts of interest to declare.

Abbreviations

The following abbreviations are used in this manuscript:
AICLDautoimmune cholestatic liver disease
ALPalkaline phosphatase
ALTalanine aminotransferase
ASTaspartate aminotransferase
ATXautotaxin
BAbile acid
BIDbis in die
C47-alpha-hydroxy-4-cholesten-3-one
CIconfidence interval
FGF19fibroblast growth factor 19
GGTgamma-glutamyl transferase
IBATileal bile acid transporter inhibitors
IBDinflammatory bowel disease
MDmean difference
MOS-Sleepmedical outcomes study sleep scale
NRSnumber rating scale
PBCprimary biliary cholangitis
PPARperoxisome proliferator-activated receptor
PSCprimary sclerosing cholangitis
QDquaque die
RCTrandomized controlled trial
RoB2Cochrane risk of bias assessment tool
ROBINS-Irisk of bias in non-randomized studies of interventions
SDstandard deviation
SEstandard error
TBtotal bilirubin
TEAEstreatment-emergent adverse events
UDCAursodeoxycholic acid

References

  1. Sarcognato, S.; Sacchi, D.; Grillo, F.; Cazzagon, N.; Fabris, L.; Cadamuro, M.; Cataldo, I.; Covelli, C.; Mangia, A.; Guido, M. Autoimmune biliary diseases: Primary biliary cholangitis and primary sclerosing cholangitis. Pathologica 2021, 113, 170–184. [Google Scholar] [CrossRef]
  2. Lazaridis, K.N.; LaRusso, N.F. The cholangiopathies. Mayo Clin. Proc. 2015, 90, 791–800. [Google Scholar] [CrossRef]
  3. Lazaridis, K.N.; Strazzabosco, M.; LaRusso, N.F. The cholangiopathies: Disorders of biliary epithelia. Gastroenterology 2004, 127, 1565–1577. [Google Scholar] [CrossRef]
  4. Cançado, G.G.L.; Deeb, M.; Gulamhusein, A.F. Liver transplantation for cholestatic liver diseases: Timing & disease recurrence. Hepatology 2025. [Google Scholar] [CrossRef]
  5. Wunsch, E.; Krause, L.; Gevers, T.J.; Schramm, C.; Janik, M.K.; Krawczyk, M.; Willemse, J.; Uhlenbusch, N.; Löwe, B.; Lohse, A.W.; et al. Confidence in treatment is contributing to quality of life in autoimmune liver diseases: The results of ERN RARE-LIVER online survey. Liver Int. 2022, 43, 381–392. [Google Scholar] [CrossRef]
  6. Mells, G.F.; Pells, G.; Newton, J.L.; Bathgate, A.J.; Burroughs, A.K.; Heneghan, M.A.; Neuberger, J.M.; Day, D.B.; Ducker, S.J.; Sandford, R.N.; et al. Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study. Hepatology 2013, 58, 273–283. [Google Scholar] [CrossRef]
  7. Schramm, C.; Wahl, I.; Weiler-Normann, C.; Voigt, K.; Wiegard, C.; Glaubke, C.; Brähler, E.; Löwe, B.; Lohse, A.W.; Rose, M. Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis. J. Hepatol. 2014, 60, 618–624. [Google Scholar] [CrossRef] [PubMed]
  8. Haapamäki, J.; Tenca, A.; Sintonen, H.; Barner-Rasmussen, N.; Färkkilä, M.A. Health-related quality of life among patients with primary sclerosing cholangitis. Liver Int. 2014, 35, 2194–2201. [Google Scholar] [CrossRef] [PubMed]
  9. Tajiri, K.; Shimizu, Y. Recent advances in the management of pruritus in chronic liver diseases. World J. Gastroenterol. 2017, 23, 3418. [Google Scholar] [CrossRef] [PubMed]
  10. Jin, X.Y.; Khan, T.M. Quality of life among patients suffering from cholestatic liver disease-induced pruritus: A systematic review. J. Formos. Med. Assoc. 2016, 115, 689–702. [Google Scholar] [CrossRef]
  11. Beuers, U.; Wolters, F.; Oude Elferink, R.P.J. Mechanisms of pruritus in cholestasis: Understanding and treating the itch. Nat. Rev. Gastroenterol. Hepatol. 2022, 20, 26–36. [Google Scholar] [CrossRef]
  12. Verkade, H.J.; Felzen, A.; Keitel, V.; Thompson, R.; Gonzales, E.; Strnad, P.; Kamath, B.; van Mil, S. EASL Clinical Practice Guidelines on genetic cholestatic liver diseases. J. Hepatol. 2024, 81, 303–325. [Google Scholar] [CrossRef] [PubMed]
  13. Bowlus, C.L.; Arrivé, L.; Bergquist, A.; Deneau, M.; Forman, L.; Ilyas, S.I.; Lunsford, K.E.; Martinez, M.; Sapisochin, G.; Shroff, R.; et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2022, 77, 659–702. [Google Scholar] [CrossRef] [PubMed]
  14. Lindor, K.D.; Bowlus, C.L.; Boyer, J.; Levy, C.; Mayo, M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology 2022, 75, 1012–1013. [Google Scholar] [CrossRef] [PubMed]
  15. Bhushan, S.; Sohal, A.; Kowdley, K.V. Primary biliary cholangitis and primary sclerosing cholangitis therapy landscape. Am. J. Gastroenterol. 2024, 120, 151–158. [Google Scholar] [CrossRef]
  16. Corpechot, C.; Chazouillères, O.; Rousseau, A.; Le Gruyer, A.; Habersetzer, F.; Mathurin, P.; Goria, O.; Potier, P.; Minello, A.; Silvain, C.; et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N. Engl. J. Med. 2018, 378, 2171–2181. [Google Scholar] [CrossRef]
  17. Hirschfield, G.M.; Bowlus, C.L.; Mayo, M.J.; Kremer, A.E.; Vierling, J.M.; Kowdley, K.V.; Levy, C.; Villamil, A.; Ladrón de Guevara Cetina, A.L.; Janczewska, E.; et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N. Engl. J. Med. 2024, 390, 849–861. [Google Scholar] [CrossRef]
  18. Kowdley, K.V.; Bowlus, C.L.; Levy, C.; Akarca, U.S.; Alvares-Da-Silva, M.R.; Andreone, P.; Arrese, M.; Corpechot, C.; Francque, S.M.; Heneghan, M.A.; et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N. Engl. J. Med. 2024, 390, 795–805. [Google Scholar] [CrossRef]
  19. de Vries, E.; Bolier, R.; Goet, J.; Parés, A.; Verbeek, J.; de Vree, M.; Drenth, J.; van Erpecum, K.; van Nieuwkerk, K.; van der Heide, F.; et al. Fibrates for itch (FITCH) in fibrosing cholangiopathies: A double-blind, randomized, placebo-controlled trial. Gastroenterology 2021, 160, 734–743.e6. [Google Scholar] [CrossRef]
  20. McNally, B.B.; Carey, E.J. Cholestatic liver diseases: Modern therapeutics. Expert Rev. Gastroenterol. Hepatol. 2025, 19, 365–370. [Google Scholar] [CrossRef]
  21. Al-Dury, S.; Marschall, H.U. Ileal bile acid transporter inhibition for the treatment of chronic constipation, cholestatic pruritus, and NASH. Front Pharmacol. 2018, 9, 931. [Google Scholar] [CrossRef]
  22. Muntaha, H.S.T.; Munir, M.; Sajid, S.H.; Sarfraz, Z.; Sarfraz, A.; Robles-Velasco, K.; Sarfraz, M.; Felix, M.; Cherrez-Ojeda, I. Ileal bile acid transporter blockers for cholestatic liver disease in pediatric patients with Alagille syndrome: A systematic review and meta-analysis. J. Clin. Med. 2022, 11, 7526. [Google Scholar] [CrossRef]
  23. Imran, M.; Elsnhory, A.B.; Ibrahim, A.A.; Elnaggar, M.; Tariq, M.S.; Mehmood, A.M.; Ali, S.; Khalil, S.; Khan, S.H.; Ali, M.; et al. Efficacy and safety of ileal bile acid transport inhibitors in inherited cholestatic liver disorders: A meta-analysis of randomized controlled trials. J. Clin. Exp. Hepatol. 2025, 15, 102462. [Google Scholar] [CrossRef] [PubMed]
  24. Levy, C.; Kendrick, S.; Bowlus, C.L.; Tanaka, A.; Jones, D.; Kremer, A.E.; Mayo, M.J.; Haque, N.; von Maltzahn, R.; Allinder, M.; et al. GLIMMER: A randomized phase 2b dose-ranging trial of linerixibat in primary biliary cholangitis patients with pruritus. Clin. Gastroenterol. Hepatol. 2023, 21, 1902–1912.e13. [Google Scholar] [CrossRef] [PubMed]
  25. Bowlus, C.L.; Eksteen, B.; Cheung, A.C.; Thorburn, D.; Moylan, C.A.; Pockros, P.J.; Forman, L.M.; Dorenbaum, A.; Hirschfield, G.M.; Kennedy, C.; et al. Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study. Hepatol. Commun. 2023, 7, e0153. [Google Scholar] [CrossRef] [PubMed]
  26. Mayo, M.J.; Pockros, P.J.; Jones, D.; Bowlus, C.L.; Levy, C.; Patanwala, I.; Bacon, B.; Luketic, V.; Vuppalanchi, R.; Medendorp, S.; et al. A randomized, controlled, phase 2 study of maralixibat in the treatment of itching associated with primary biliary cholangitis. Hepatol. Commun. 2019, 3, 365–381. [Google Scholar] [CrossRef]
  27. Higgins, J.P.T.; Thomas, J.; Chandler, J.; Cumpston, M.; Li, T.; Page, M.J.; Welch, V.A. (Eds.) Cochrane Handbook for Systematic Reviews of Interventions; Version 6.5; Cochrane: London, UK, 2024. [Google Scholar]
  28. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  29. Page, M.J.; Moher, D.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews. BMJ 2021, 372, n160. [Google Scholar] [CrossRef]
  30. Ouzzani, M.; Hammady, H.; Fedorowicz, Z.; Elmagarmid, A. Rayyan—A web and mobile app for systematic reviews. Syst. Rev. 2016, 5, 210. [Google Scholar] [CrossRef]
  31. Lindor, K.D.; Gershwin, M.E.; Poupon, R.; Kaplan, M.; Bergasa, N.V.; Heathcote, E.J. American Association for the Study of Liver Diseases. Primary biliary cirrhosis. Hepatology 2009, 50, 291–308. [Google Scholar] [CrossRef]
  32. Chapman, R.; Fevery, J.; Kalloo, A.; Nagorney, D.M.; Boberg, K.M.; Shneider, B.; Gores, G.J. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010, 51, 660–678. [Google Scholar] [CrossRef]
  33. Mayo, M.J.; Carey, E.; Smith, H.T.; Mospan, A.R.; McLaughlin, M.; Thompson, A.; Morris, H.L.; Sandefur, R.; Kim, W.R.; Bowlus, C.; et al. Impact of pruritus on quality of life and current treatment patterns in patients with primary biliary cholangitis. Dig. Dis. Sci. 2022, 68, 995–1005. [Google Scholar] [CrossRef]
  34. Smith, H.T.; de Souza, A.R.; Thompson, A.H.; McLaughlin, M.M.; Dever, J.J.; Myers, J.A.; Chen, J.V. Cholestatic pruritus treatments in primary biliary cholangitis and primary sclerosing cholangitis: A systematic literature review. Dig. Dis. Sci. 2023, 68, 2710–2730. [Google Scholar] [CrossRef] [PubMed]
  35. Kanda, T.; Sasaki-Tanaka, R.; Kimura, N.; Abe, H.; Yoshida, T.; Hayashi, K.; Sakamaki, A.; Yokoo, T.; Kamimura, H.; Tsuchiya, A.; et al. Pruritus in chronic cholestatic liver diseases, especially in primary biliary cholangitis: A narrative review. Int. J. Mol. Sci. 2025, 26, 1883. [Google Scholar] [CrossRef] [PubMed]
  36. Karatza, E.; Swift, B.; Carreño, F.; Mukherjee, S.; Casillas, L.; Lennie, J.; Fettiplace, J.; McLaughlin, M.M.; Kremer, A.E. Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat. Liver Int. 2024, 44, 2293–2302. [Google Scholar] [CrossRef]
  37. Hegade, V.S.; Pechlivanis, A.; McDonald, J.A.K.; Rees, D.; Corrigan, M.; Hirschfield, G.M.; Taylor-Robinson, S.D.; Holmes, E.; Marchesi, J.R.; Kendrick, S.; et al. Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus. Liver Int. 2019, 39, 967–975. [Google Scholar] [CrossRef]
  38. Jacoby, A. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut 2005, 54, 1622–1629. [Google Scholar] [CrossRef]
  39. Al-Dury, S.; Wahlström, A.; Wahlin, S.; Langedijk, J.; Elferink, R.O.; Ståhlman, M.; Marschall, H.-U. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis. Sci. Rep. 2018, 8, 6658. [Google Scholar] [CrossRef]
  40. Tanaka, A.; Atsukawa, M.; Tsuji, K.; Notsumata, K.; Suyama, A.; Ito, H.; Das, S.; von Maltzahn, R.; McLaughlin, M.M. Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis. Hepatol. Res. 2023, 53, 629–640. [Google Scholar] [CrossRef]
  41. von Maltzahn, R.; Mayo, M.J.; Smith, H.T.; Thompson, A.; Das, S.; de Souza, A.R.; Lisi, E.; Levy, C.; McLaughlin, M.M.; Jones, D. Relationship between pruritus and sleep in participants with primary biliary cholangitis in the Phase 2b GLIMMER trial. J. Patient Rep. Outcomes 2024, 8, 60. [Google Scholar] [CrossRef]
  42. Carreño, F.; Karatza, E.; Mehta, R.; Collins, J.; Austin, D.; Swift, B. Population dose–response–time analysis of itch reduction and patient-reported tolerability supports Phase III dose selection for linerixibat. Clin. Pharmacol. Ther. 2023, 115, 288–298. [Google Scholar] [CrossRef]
  43. Carreño, F.; Mehta, R.; de Souza, A.R.; Collins, J.; Swift, B. Analysis of C4 concentrations to predict impact of patient-reported diarrhea associated with the ileal bile acid transporter inhibitor linerixibat. CPT Pharmacomet. Syst. Pharmacol. 2025, 14, 596–605. [Google Scholar] [CrossRef]
Gastroent 16 00030 g001
Figure 1. PRISMA 2020 flow diagram. * Other reasons for manuscript exclusion include overlapping populations, absence of the outcome of interest, irrelevant population, editorial articles, and interventions not of interest.
Figure 1. PRISMA 2020 flow diagram. * Other reasons for manuscript exclusion include overlapping populations, absence of the outcome of interest, irrelevant population, editorial articles, and interventions not of interest.
Gastroent 16 00030 g001
Gastroent 16 00030 g002
Figure 2. Forest plot illustrating the mean change in the 5-D Itch score [24,25,26].
Figure 2. Forest plot illustrating the mean change in the 5-D Itch score [24,25,26].
Gastroent 16 00030 g002
Gastroent 16 00030 g003
Figure 3. Forest plot illustrating the mean change in the MOS Sleep Scale [25,26].
Figure 3. Forest plot illustrating the mean change in the MOS Sleep Scale [25,26].
Gastroent 16 00030 g003
Gastroent 16 00030 g004
Figure 4. Forest plot illustrating the mean change in serum biochemistry levels: (A) alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) gamma-glutamyl transferase (GGT), and (D) total bilirubin (TB) [24,26].
Figure 4. Forest plot illustrating the mean change in serum biochemistry levels: (A) alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) gamma-glutamyl transferase (GGT), and (D) total bilirubin (TB) [24,26].
Gastroent 16 00030 g004
Gastroent 16 00030 g005
Figure 5. Forest plots illustrating the pooled proportion of patients experiencing (A) any adverse event, (B) serious adverse events, and (C) treatment discontinuation due to adverse effects [24,25,26].
Figure 5. Forest plots illustrating the pooled proportion of patients experiencing (A) any adverse event, (B) serious adverse events, and (C) treatment discontinuation due to adverse effects [24,25,26].
Gastroent 16 00030 g005
Gastroent 16 00030 g006
Figure 6. Forest plot illustrating the pooled proportion of patients experiencing treatment-emergent adverse effects: (A) nausea, (B) abdominal pain, and (C) diarrhea [24,25,26].
Figure 6. Forest plot illustrating the pooled proportion of patients experiencing treatment-emergent adverse effects: (A) nausea, (B) abdominal pain, and (C) diarrhea [24,25,26].
Gastroent 16 00030 g006
Table 1. Baseline characteristics of included studies.
Table 1. Baseline characteristics of included studies.
StudyDesignAICLDIBAT InhibitorPatient, nDose (Frequency)Mean Age, Years (SD)Female, n (%)Receiving UDCA, n (%)Receiving Lipid-Modifying Agents, n (%)Receiving
Antihistamine, n (%)		Mean Serum BA, µmol/L (SD)Dose Escalation, WeeksFollow-Up, Weeks
Mayo 2019 [26] 1RCTPBCMaralixibat2110 mg (QD)54.7 (12.7)20 (95.2)21 (100)4 (9.5)11 (26.2)33.1 (30.6)313
Mayo 2019 [26] 2215 or 20 mg (QD)53.5 (10.5)17 (81.0)19 (90.5)52.5 (94.4)2–4
Bowlus 2023 [25]Single-armPSCMaralixibat2710 mg (QD)43.7 (11.4)9 (33.3)NA6 (22.2)NA38.9 (NA)614
Levy 2023 [24] (GLIMMER) 1RCTPBCLinerixibat1620 mg (QD)58.5 (7.3)16 (100.0)14 (87.5)NA2 (12.5)13.0 (13.8)012
Levy 2023 [24] (GLIMMER) 22390 mg (QD)52.5 (12.3)21 (91.1)22 (95.6)NA3 (13.0)33.7 (55.8)
Levy 2023 [24] (GLIMMER) 327180 mg (QD)58.9 (11.1)25 (92.6)27 (100)NA3 (11.1)26.6 (36.5)
Levy 2023 [24] (GLIMMER) 42340 mg (BID)55.6 (11.2)22 (95.6)21 (91.3)NA4 (17.4)18.6 (21.8)
Levy 2023 [24] (GLIMMER) 52290 mg (BID)56.2 (11.3)20 (90.9)21 (95.4)NA3 (13.6)19.3 (31.0)
AICLD, autoimmune cholestatic liver disease; BA, bile acid; BID, twice daily; IBAT, ileal bile acid transporter; NA, not available; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; QD, once daily; RCT, randomized control trial; SD, standard deviation; and UDCA, ursodeoxycholic acid.
Table 2. Summary of findings by drug use.
Table 2. Summary of findings by drug use.
IBAT InhibitorAICLD StudiedMechanism of ActionIndicationMain FindingsAdverse Effects
LinerixibatPBCInterruption of intestinal bile acid reabsorption Second-line therapy for pruritus in patients with AICLDSignificantly reduced pruritus severity (Levy 2023) [24], with improvements in itch intensity (MWDI score) and quality of life (PBC-40 itch, social, and emotional domains) compared to placebo; biomarker analysis also showed favorable changes.Dose-related GI AEs, chiefly diarrhea (38–68% across doses) and abdominal pain (9–30%); nausea occurred less frequently. Some discontinuations due to diarrhea/abdominal pain; events resolved after stopping treatment.
MaralixibatPBC and PSCPBC (Mayo 2019) [26]: reduced pruritus severity with improvements in patient-reported itch scores (ItchRO, VAS) and quality of life.
PSC (Bowlus 2023) [25]: reduced serum bile acids and modest pruritus improvements (ItchRO, 5-D itch), greater in those with more severe baseline itch.
Both studies reported improvements in biomarkers analysis.		PBC (Mayo 2019) [26]: GI disorders in 78.6% vs. 50.0% with placebo; most frequent were diarrhea 61.9%, abdominal pain 23.8%, upper abdominal pain 23.8%, nausea 23.8%; fewer events during stable dosing and most resolved without discontinuation.
PSC (Bowlus 2023) [25]: GI TEAEs in 81.5%; diarrhea 51.9%, nausea 33.3%, abdominal pain 29.6%; GI events were more common during dose escalation than stable dosing; one treatment-related serious AE (cholangitis).
5-D itch, 5-dimensional itch scale; AE, adverse event; AICLD, autoimmune cholestatic liver disease; GI, gastrointestinal; IBAT, ileal bile acid transporter; ItchRO, itch reported outcome; MWDI, mean worst daily itch; PBC, primary biliary cholangitis; PBC-40, primary biliary cholangitis-40 (disease-specific quality of life questionnaire); PSC, primary sclerosing cholangitis; TEAE, treatment-emergent adverse event; and VAS, visual analog scale.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Silveira, I.B.; Rezende, R.A.A.; Neto, C.A.M.L.; Rossi, Y.I.; Leite, M.d.A.B.C.; Cançado, G.G.L. Ileal Bile Acid Transporter Inhibitors for Adult Patients with Autoimmune Cholestatic Liver Diseases: A Systematic Review and Meta-Analysis. Gastroenterol. Insights 2025, 16, 30. https://doi.org/10.3390/gastroent16030030

AMA Style

Silveira IB, Rezende RAA, Neto CAML, Rossi YI, Leite MdABC, Cançado GGL. Ileal Bile Acid Transporter Inhibitors for Adult Patients with Autoimmune Cholestatic Liver Diseases: A Systematic Review and Meta-Analysis. Gastroenterology Insights. 2025; 16(3):30. https://doi.org/10.3390/gastroent16030030

Chicago/Turabian Style

Silveira, Igor Boechat, Rodolfo Augusto Assis Rezende, Carlos Alberto Monteiro Leitão Neto, Yohanna Idsabella Rossi, Marina de Assis Bezerra Cavalcanti Leite, and Guilherme Grossi Lopes Cançado. 2025. "Ileal Bile Acid Transporter Inhibitors for Adult Patients with Autoimmune Cholestatic Liver Diseases: A Systematic Review and Meta-Analysis" Gastroenterology Insights 16, no. 3: 30. https://doi.org/10.3390/gastroent16030030

APA Style

Silveira, I. B., Rezende, R. A. A., Neto, C. A. M. L., Rossi, Y. I., Leite, M. d. A. B. C., & Cançado, G. G. L. (2025). Ileal Bile Acid Transporter Inhibitors for Adult Patients with Autoimmune Cholestatic Liver Diseases: A Systematic Review and Meta-Analysis. Gastroenterology Insights, 16(3), 30. https://doi.org/10.3390/gastroent16030030

Article Metrics

Back to TopTop