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

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.

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