Exploration of Digestive Diseases

Table 2. Therapeutic agents in PBC and MASLD.

Agent	Mechanism	PBC	MASLD/MASH
UDCA	Hydrophilic bile acid, cytoprotective and anti- cholestatic	First-line therapy	No proven histologic benefit; may improve liver enzymes
OCA	FXR agonist	Second-line for inadequate UDCA responders	Improves fibrosis in REGENERATE trial; did not receive FDA approval for MASH
Elafibranor	PPARα/δ dual agonist	FDA-approved (ELATIVE)	Failed to meet primary endpoint in phase 3 (RESOLVE-IT)
Fibrates	PPARα agonist	Improve cholestasis, may normalize ALP	Used for dyslipidemia management
Statins	HMG-CoA reductase inhibitor, anti-inflammatory and antifibrotic effects	Safe; emerging evidence suggests potential liver benefit	Associated with reduced steatosis, fibrosis progression, liver-related events and mortality
Resmetirom	THR-β agonist	Not studied in PBC	First FDA-approved MASH therapy (F2–F3 fibrosis, 2024)

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ALP: alkaline phosphatase; FXR: farnesoid X receptor; HMG-CoA: 3-hydroxy-3-methylglutaryl coenzyme A; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; OCA: obeticholic acid; PBC: primary biliary cholangitis; PPAR: peroxisome proliferator-activated receptor; UDCA: ursodeoxycholic acid.

Declarations

Author contributions

MM: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MA: Investigation, Writing—original draft, Writing—review & editing. WKS: Validation, Supervision, Writing—review & editing. KQ: Supervision, Validation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Kamran Qureshi, MD, has received honoraria from Madrigal Pharmaceuticals, Gilead Sciences, and Salix Pharmaceuticals as a member of the speaker bureau. The other authors declare no conflicts of interest relevant to this work.

Ethical approval

Not applicable.

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Funding

The authors received no specific funding for this work.

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