Abstract
Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy, typically presenting in the third trimester. It is characterized by pruritus, elevated serum bile acids, and abnormal liver function tests. While maternal symptoms resolve postpartum, ICP poses significant risks to fetal health, including spontaneous preterm labor, meconium-stained amniotic fluid, and stillbirth. This review aims to synthesize current knowledge on the pathogenesis, diagnosis, and management and highlight emerging research and possible therapy directions in ICP. A comprehensive review of recent literature was conducted, focusing on molecular mechanisms, clinical management guidelines, fetal outcomes, and novel therapeutics under investigation. Ursodeoxycholic acid (UDCA) remains the primary pharmacologic treatment of intrahepatic cholestasis of pregnancy; however, its effect on perinatal outcomes is debated. Investigational therapies—including Volixibat, FXR agonists, 4-phenylbutyrate, and NorUDCA—are under exploration. These emerging therapies hold the potential to improve both maternal symptoms and perinatal outcomes by addressing the underlying pathophysiology of ICP more effectively than current standard treatment. Additionally, emerging biomarkers and machine-learning tools hold promise for improved diagnosis and personalized care. ICP continues to pose diagnostic and therapeutic challenges. While maternal outcomes are generally favorable, optimizing fetal safety requires timely diagnosis, stratified risk assessment, and evidence-based delivery planning. Future research should prioritize identifying predictive biomarkers, refining treatment algorithms, and assessing long-term outcomes for both mothers and offspring. Special attention should also be given to the investigation of novel therapeutic targets.