What Are Risk Factors for Nonanastomotic Biliary Strictures Post-Liver Transplantation?

Cold and warm ischemia times and total operative time were among the 7 risk factors researchers identified.

Researchers have identified 7 prognostic factors that are associated with a significant risk for nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation, including donation after circulatory death (DCD) donor vs donation after brain death (DBD) donor and having primary sclerosing cholangitis (PSC) as an indication, according to a study in Digestive Diseases and Sciences.

The systematic review and meta-analysis evaluated the strength of association of prognostic factors for NAS after orthotopic liver transplantation.

Investigators searched the PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies that assessed at least 1 risk factor for NAS after liver transplantation. They followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. The Newcastle-Ottawa scale was used to assess study quality.

A risk factor was pooled across the included studies if the same factor was reported in 2 or more studies.

[F]urther research is required to identify the mechanisms underlying these risk factors.

The meta-analysis included 19 studies with 8269 patients who had a liver transplant, of whom 680 patients developed NAS. Among the included studies, 16 were retrospective cohorts, 2 were prospective cohorts, and 1 was a case-control study. Participants’ mean age was 50.0 years, and 53.9% were men.

Participants who received livers from DCD donors vs DBD donors were more likely to develop NAS (odds ratio [OR], 2.70; 95% CI, 1.13-6.47; P =.03; I2=51%). Transplant recipients with an indication for PSC were more likely to develop NAS vs those with other etiologies (OR, 2.15; 95% CI, 1.28-3.62; P =.004; I2=49%). Liver transplants involving cytomegalovirus mismatch (donor positive/recipient negative) were less likely to be associated with NAS (OR, 0.61; 95% CI, 0.38-0.96; P =.03; I2=0%).

Patients who had Roux-en-Y bile duct reconstruction had an increased risk for NAS compared with those who had duct-to-duct reconstruction (OR, 2.20; 95% CI, 1.62-2.99; P <.00001; I2=0%). Cold ischemia time (P =.003), warm ischemia time (P =.04), and total operative time (P <.05) were also associated with an increased risk for NAS.

A shorter length of intensive care unit stay was associated with a reduced risk for NAS (mean difference, -0.65 days; 95% CI, 1.24 to -0.06; P =.03; I2=0%). Transplant recipients with hepatic artery thrombosis were more likely to develop NAS (OR, 9.68; 95% CI, 4.64-20.19; P <.00001; I2=0%).

In pooled univariate HRs of NAS risk factors, donor type (DCD vs DBD; HR, 2.20; 95% CI, 1.19-4.05; P =.01; I2=67%) and cold ischemia time (HR, 1.12; 95% CI, 1.04-1.20; P =.0002; I2=0%) were associated with an increased risk for NAS.

The main study limitation is the absence of prospective randomized trials in the analyses. Also, the search strategy had a small risk of missed data that might have been available in nontraditional publications, and significant heterogeneity was observed for multiple risk factors.

“Multicenter prospective studies are required to corroborate our results, and to elucidate the most important of these 7 risk factors,” the study authors noted. “Additionally, further research is required to identify the mechanisms underlying these risk factors.”


Fasullo M, Ghazaleh S, Sayeh W, et al. Prognostic factors for non‑anastomotic biliary strictures following adult liver transplantation: a systematic review and meta‑analysis. Dig Dis Sci. Published online February 9, 2023. doi:10.1007/s10620-023-07861-0