Published online Sep 18, 2026. doi: 10.13105/wjma.120937
Revised: June 5, 2026
Accepted: June 26, 2026
Published online: September 18, 2026
Processing time: 184 Days and 3.3 Hours
Cholestatic pruritus (CP) is a debilitating symptom affecting patients with primary biliary cholangitis (PBC), primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, drug-induced cholestasis, and other hepatobiliary disorders. Despite its clinical significance, the pathogenesis remains multifactorial, involving bile acids, autotaxin-lysophosphatidic acid signaling, and endogenous opioids. Recent advances in noninvasive biomarkers and therapeutic options necessitate an updated synthesis of evidence.
To systematically review contemporary diagnostic modalities and evaluate the safety and efficacy of available therapies of CP.
A systematic search of PubMed, EMBASE, and Web of Science (through February 2026) identified studies assessing diagnostic markers or treatments for CP. Eligible publications included randomized controlled trials, observational studies, systematic reviews, and guideline statements. Data were extracted on diagnostic accuracy, treatment responses, adverse effects, and comparative effectiveness. The review followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
Serum autotaxin levels demonstrated moderate correlation with pruritus severity, though clinical scoring systems remain essential due to significant patient variability. Traditional first-line therapy with bile acid sequestrants have minimal evidence for their efficacy although they demonstrate a favorable side-effect profile. Fibrates serve as a more effective first-line therapy in the case of PBC and primary sclerosing cholangitis. Rifampin demonstrated consistent efficacy through pregnane X receptor induction. Opioid antagonists (e.g., naltrexone) and sertraline provided relief in refractory cases. Newly approved ileal bile acid transporter inhibitors significantly reduced pruritus in PBC and pediatric cholestatic disorders. Phototherapy (narrow-band ultraviolet B), dermatology co-management, and multidisciplinary supportive care may be beneficial in specialized populations. Adverse effects and drug-drug interactions remain important limiting factors.
CP requires a structured, stepwise approach integrating biomarkers, symptom scores, targeted therapies, and multidisciplinary involvement. Newer options, like fibrates and ileal bile acid transporter inhibitors, and personalized combination therapy represent promising advances.
Core Tip: Cholestatic pruritus is a common and debilitating symptom in cholestatic liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis. Its pathogenesis is multifactorial, involving bile acids, autotaxin-lysophosphatidic acid signaling, and endogenous opioids. This systematic review summarizes contemporary diagnostic approaches and treatment strategies. Serum autotaxin correlates moderately with itch severity but should be interpreted alongside validated clinical pruritus scales. While bile acid sequestrants remain the traditional first-line therapy due to safety, evidence for efficacy is limited. Fibrates show increasing effectiveness, particularly in primary biliary cholangitis and primary sclerosing cholangitis. Rifampin, opioid antagonists, sertraline, and newer ileal bile acid transporter inhibitors provide options for refractory disease. A stepwise, multidisciplinary approach is essential to optimize outcomes.