Pathophysiology and Pharmacotherapy of Cholelithiasis: A Comprehensive Review

Author

Sanusha T.V., Dr. Abdul Vahab A., Dr. Jyoti Harindran

Abstract

 Cholelithiasis represents a widespread metabolic and hepatobiliary disorder affecting up to twenty percent of adults worldwide, contributing to substantial morbidity, direct healthcare expenditures, and diminished quality of life. The clinical cornerstone of definitive intervention remains laparoscopic cholecystectomy; however, surgical excision does not resolve the root metabolic aberrations governing lithogenesis and disrupts endogenous enterohepatic bile acid circulation, carrying secondary risks of postcholecystectomy diarrhea, metabolic syndrome, and altered gut microbiome dynamics. Understanding the mechanistic foundations of cholesterol and pigment gallstone formation has unveiled promising pharmacological targets. Supersaturation of bile with cholesterol arises from coordinated dysregulation across hepatic lipid transporters, defective nuclear receptor signaling, hypersecretion of gallbladder mucin, impaired neurohormonal contractility, and accelerated hydrophobic crystallization. While ursodeoxycholic acid (UDCA) serves as the primary non-surgical therapeutic agent, its prolonged treatment duration, incomplete dissolution efficacy against calcified or mixed stones, and post-cessation recurrence rates highlight the necessity for optimized medical alternatives. Emerging approaches focus on dual therapies combining bile desaturating agents with intestinal cholesterol uptake blockers, selective nuclear receptor agonists, and antioxidant-rich plant bioactives capable of attenuating inflammatory and oxidative insults within the biliary epithelium. Furthermore, translating these interventions through targeted genetic risk stratification and tailored combination regimens offers a viable route toward organ-preserving pharmacotherapy. This comprehensive review delineates the pathophysiology, molecular transport networks, conventional medications, novel drug candidates, and preclinical natural bioactives in cholelithiasis, providing an integrated roadmap for non-surgical hepatobiliary care.

Keywords

Cholelithiasis; Pathophysiology; Pharmacotherapy; Ursodeoxycholic acid; ABCG5/ABCG8; Phytotherapy; Bile acid metabolism.

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