Introduction
Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease characterized by progressive inflammation, fibrosis, and stricturing of the intra- and extrahepatic medium-large bile ducts. Due to its progressive nature, PSC can lead to life-threatening complications, including recurrent cholangitis, cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma. Liver transplantation (LT) remains the only definitive treatment for patients with advanced disease. However, recurrence of PSC (rPSC) after LT remains a significant clinical challenge. Understanding recipient and donor factors associated with rPSC is crucial to optimizing patient care.
Aims & Methods
This systematic review and meta-analysis aimed to identify risk and protective factors associated with PSC recurrence following LT. The study followed PRISMA guidelines. Comprehensive searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL. Eligible studies included full-text articles reporting on LT for PSC with recurrence data. Conference abstracts and studies lacking data on recurrence predictors were excluded. Pooled estimates were calculated using a random-effects model, and heterogeneity was assessed with the I² statistic. Statistical analyses were performed using R Studio.
Results
Twenty-eight studies were included, comprising 4,161 patients who underwent LT for PSC (62.8% male). Most data originated from Europe (46.5%) and North America (31.9%), with additional cohorts from Asia (15.4%), South America (3.2%), and Oceania (3%). The reported rPSC rate ranged from 0% to 36.5%, with a pooled recurrence proportion of 18.5% (95% CI: 14.9-22.1%). Significant protective factors for rPSC included older recipient age (mean difference [MD] = 5.22 years, 95% CI: 3.62-6.82), male sex (risk ratio [RR] = 0.91, 95% CI: 0.86-0.97), younger donor age (MD = - 3.78 years, 95% CI: [-6.16; - 1.39]), and post-LT cyclosporine use (RR = 0.60, 95% CI: 0.40-0.91), while acute rejection episodes were associated with an increased risk of recurrence (RR = 1.61, 95% CI: 1.10-2.36). No significant associations were found with donor sex, donor-recipient sex mismatch, pre-LT inflammatory bowel disease diagnosis, pre/post-LT colectomy, pre-LT MELD score, recipient cytomegalovirus status, type of graft (deceased or living donor), hepaticojejunostomy, cold and warm ischemia times, or post-LT tacrolimus use.
Conclusion
This updated meta-analysis, encompassing 4,161 patients across four continents, estimates a pooled rPSC rate of 18.5%. Older recipient age, male sex, younger donor age, and cyclosporine use post-LT were associated with a lower risk of rPSC, while acute rejection episodes were associated with a higher risk of recurrence. These findings may inform clinical decision-making and support future research into strategies to reduce PSC recurrence following liver transplantation. Additional multicenter prospective studies are warranted to validate these results.
Disclosure
Rodrigo V. Motta, MD has received a research grant from PSC Support. Guilherme G. L. Cançado, MD, PhD has received a research grant from IPSEN. This study was conducted without funding support.
