Drazilova S, Jarcuska P, Koky T, Harhovsky M, Komarova S, Vasil J, Janicko M. Second-line treatment of primary biliary cholangitis: To whom, which molecule, and when. World J Hepatol 2026; 18(8): 121491 [DOI: 10.4254/wjh.121491]
Corresponding Author of This Article
Peter Jarcuska, MD, PhD, Professor, 2nd Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice 04011, Slovakia. peter.jarcuska@upjs.sk
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Drazilova S, Jarcuska P, Koky T, Harhovsky M, Komarova S, Vasil J, Janicko M. Second-line treatment of primary biliary cholangitis: To whom, which molecule, and when. World J Hepatol 2026; 18(8): 121491 [DOI: 10.4254/wjh.121491]
World J Hepatol. Aug 27, 2026; 18(8): 121491 Published online Aug 27, 2026. doi: 10.4254/wjh.121491
Second-line treatment of primary biliary cholangitis: To whom, which molecule, and when
Sylvia Drazilova, Peter Jarcuska, Tomas Koky, Martin Harhovsky, Slavomira Komarova, Jan Vasil, Martin Janicko
Sylvia Drazilova, Peter Jarcuska, Tomas Koky, Martin Harhovsky, Slavomira Komarova, Jan Vasil, Martin Janicko, 2nd Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice 04011, Slovakia
Author contributions: Drazilova S, and Jarcuska P participated in the design of the manuscript; Drazilova S, Jarcuska P, Koky T, Harhovsky M, Komarova S and Vasil J participated in data collection of the manuscript and writing-original draft; Drazilova S, Jarcuska P, and Janicko M participated in writing-review and editing. All authors have read and approved the final manuscript.
AI contribution statement: No artificial intelligence tools were used in the preparation of this manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Peter Jarcuska, MD, PhD, Professor, 2nd Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice 04011, Slovakia. peter.jarcuska@upjs.sk
Received: March 26, 2026 Revised: June 23, 2026 Accepted: July 9, 2026 Published online: August 27, 2026 Processing time: 145 Days and 19.9 Hours
Abstract
Ursodeoxycholic acid (UDCA) is the first-line treatment of primary biliary cholangitis (PBC). Approximately two-thirds of patients have a biochemical response to UDCA, but only one-third of treated patients achieve a complete biochemical response. UDCA nonresponse is associated with hepatic decompensation and higher liver-related mortality; therefore, UDCA nonresponders should be considered for second-line PBC treatment. Nonfibrate peroxisome proliferator-activated receptor (PPAR) agonists elafibranor and seladelpar are approved for second-line PBC treatment in UDCA nonresponders and in UDCA treatment intolerance. Fibrates are an alternative second-line PBC therapy, but they are not approved for second-line treatment. A significant benefit of PPAR receptor agonists therapy is the alleviation of pruritus in some patients. Second-line PBC treatment is usually indicated after 1 year of UDCA therapy; however, it may be considered after 6 months of UDCA treatment in high-risk PBC patients. The selection of drug for second-line PBC treatment and the timing of therapy initiation should be individualized. Many factors, including PBC complications, especially pruritus, should also be considered in the decision-making algorithm. It will be necessary in the coming years to evaluate the efficacy of PPAR agonists in real-world clinical practice, including monitoring the incidence of decompensated liver cirrhosis and liver-related mortality.
Core Tip: Primary biliary cholangitis (PBC) is a disease with increasing prevalence, particularly in developed countries. First-line treatment of choice is ursodeoxycholic acid (UDCA), but only about two-thirds of patients achieve biochemical response. UDCA nonresponders have a higher risk of liver cirrhosis decompensation and poorer transplant-free survival. These patients should be considered for second-line therapy. This review provides a comprehensive overview of second-line treatment indications, selection of the most appropriate medication, timing of therapy initiation, benefits, and adverse effects of therapy, as well as the administration of second-line treatment in specific groups of PBC patients.
