Living Donor Liver Transplantation Linked to Better Post-Transplant Survival in PSC

New research is shedding light on the benefits of living donor liver transplantation (LDLT) in patients with primary sclerosing cholangitis (PSC), highlighting better rates of post-transplant survival than deceased donor liver transplantation (DDLT).1

Findings from the systematic review and meta-analysis highlight a 33% increase in 1-year and nearly 50% increase in 5-year post-transplant survival with LDLT versus DDLT, potentially attributable to bias to earlier referral to transplant, shorter waitlist time, and better-quality grafts as a consequence of a stricter selection of healthy donors and technical considerations such as shorter cold ischemia time.1

A chronic and progressive cholestatic liver disorder of unknown etiology, PSC is characterized by inflammation, fibrosis, and stricturing of intrahepatic or extrahepatic biliary ducts. Given its progressive nature and eventual complications of cholestasis and liver failure, median survival from the time of PSC diagnosis to death without liver transplantation is around 10 years.2

“Published studies evaluating the outcomes of LDLT in PSC patients seem to be conflicting,” Mariana Verdelho Machado, MD, of the gastroenterology clinic at the University of Lisbon, and colleagues wrote.1 “PSC patients differ from the general population of liver transplant patients in the fact that they can be eligible for transplantation in pre-cirrhotic stages and without liver failure, and might be more prone to liver transplant biliary complications. Accordingly, there is currently a lack of consensus in the recommendation of LDLT for PSC patients.”

To inform evidence-based transplant strategies for patients with PSC, investigators systematically searched PubMed, Web-of-Science, Scopus and Cochrane Central, from inception to December 2024, for studies on liver transplant recipients including PSC patients, studies classified as randomised controlled trials (RCT) or observational studies, and studies reporting ≥ 1 of the outcomes of interest (1-, 3- and 5-year survival post-transplant) in the PSC cohort, comparing LDLT to DDLT.1

The search strategy yielded an initial selection of 14,247 articles, of which 22 were included in the systematic review. In total, the studies enrolled 22,024 PSC patients, of whom 2555 were classified as LDLT and 19,439 as DDLT.1

Investigators noted DDLT recipients were more frequently male (odds ratio [OR], 1.32; 95% CI, 1.18–1.48; P <.00001; I2 = 0%) and older (mean difference [MD], 4.26 years; 95% CI, 2.42–610; P <.00001; I2 = 64%). Compared to LDLT recipients DDLT recipients presented more metabolic dysfunction with higher BMI (MD, 0.97 kg/m2; 95% CI, 0.71–1.22; P <.00001; I2 = 0%), were more likely to present type 2 diabetes (OR, 1.32; 95% CI, 1.04–1.68; P = .02; I2 = 0%), but were less likely to have inflammatory bowel disease (OR, 0.66; 95% CI, 0.50–0.87; P = .003; I2 = 0%).1

Investigators pointed out DDLT recipients presented worse liver function, with a notably higher MELD score at the time of liver transplant compared with LDLT recipients (MD, 6.63; 95% CI, 5.56–7.70; P <.00001; I2 = 72%).1

Compared with LDLT, DDLT was associated with lower 1- (93.80%; 95% CI, 93.29–94.31 vs 95.78%; 95% CI, 94.68–96.88), 3- (88.81%; 95% CI, 88.14–89.48 vs 93.23%; 95% CI, 91.85–94.61) and 5-year survival (85.18%; 95% CI, 84.43–85.92 vs 91.54%; 95% CI, 91.01–93.07), although it had no impact on graft survival.1

Further analysis of pooled data from 4 studies found a greater risk of death related to infection/sepsis after DDLT versus after LDLT (OR, 3.68; 95% CI, 1.02–13.26; P = .0003; I2 = 54%). Additionally, pooled analysis of 3 studies revealed acute rejection of the liver graft was more likely after DDLT as compared to LDLT (OR, 1.75; 95% CI, 1.12–2.73; P = .01; I2 = 0%).1

Although most individual studies failed to show differences in PSC recurrence, the pooled analysis of 12 studies revealed a 63% increased risk for DDLT as compared to LDLT (OR, 1.63; 95% CI, 1.10–2.42; P = .02; I2 = 26%). Investigators also noted the risk of biliary complications was statistically lower after DDLT (OR, 0.29; 95% CI, 0.11–0.78; P = .01; I2 = 33%), compared with LDLT in pooled analysis of 3 studies.1

“Similarly to liver transplantation in general, in PSC patients, LDLT seems to be associated with higher 1- and 5-year survival, which may be related to a bias to earlier referral to liver transplant, lower waitlist time and better-quality grafts, as a consequence of a stricter selection of healthy donors and technical considerations such as shorter cold ischemia time,” investigators concluded.1 “As such, the possibility of LDLT should be systematically inquired for patients with PSC who would benefit from liver transplant, particularly in countries with a paucity of deceased donors.”

References

1. Afonso AB, da Silva CM, Nogueira P, et al. Meta-Analysis: Comparison of Living Versus Deceased Liver Transplantation for Primary Sclerosing Cholangitis. AP&T. https://doi.org/10.1111/apt.70357

2. Rawla P, Samant H. Primary Sclerosing Cholangitis. StatPearls. February 12, 2023 Accessed September 3, 2025. https://www.ncbi.nlm.nih.gov/books/NBK537181/