NOD2 Variants and Duration of Hospitalization After Endoscopic Treatment of Biliary Strictures Following Liver Transplantation: A Cutoff-Dependent Association

Background/Objectives: Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are an important genetic risk factor that can affect the course of a disease via interaction between the gut and liver in patients with liver diseases. In this study, we investigated the effects of NOD2 variants on the hospital stay time in patients who underwent endoscopic treatment for biliary strictures after living donor liver transplantation (LDLT). Methods: Age; gender; time to endoscopic retrograde cholangiopancreatography (ERCP) after transplantation; ERCP findings; and hospitalization time of patients who underwent ERCP for biliary strictures after LDLT were recorded. The two hundred patients included in the study were divided into two groups: Group 1, discharged during the first 24 h after ERCP, and Group 2, discharged after the first 24 h following ERCP. The frequency of three NOD2 variants was investigated for the two groups. Results: The number of patients whose strictures could not be passed with endoscopic intervention in Group 2 was significantly higher than the other group (34% vs. 0%, p < 0.0001). In addition, p.R702W and 1007fs mutation frequencies in Group 2 were significantly higher than in Group 1 (10% vs. 0%, p = 0.002, and 14% vs. 3%, p = 0.011, respectively). In a Firth (bias-reduced) multivariable logistic regression including all 200 patients and adjusting for stricture-passage failure, age, CRP, and IL-6, NOD2 variant carriage remained associated with prolonged hospitalization after adjustment for the measured covariates (OR: 14.55; 95% CI: 3.06–69.04; p < 0.001), a finding corroborated by a sensitivity analysis restricted to patients with successful stricture passage (OR: 11.02; 95% CI: 2.24–54.08; p = 0.003). This association was specific to the 24 h discharge threshold used to define the primary outcome: NOD2 variant carriage was not significantly associated with length of stay when analyzed continuously (fold-change 1.27; p = 0.182) and lost statistical significance at longer discharge thresholds (>48 h; p = 0.075; >72 h; p = 0.235). Conclusions: Our findings suggest that there may be a relationship between NOD2 variants, especially the p.R702W variant, and length of hospital stay in patients undergoing ERCP after LDLT when defined by the 24 h discharge threshold used here. This cutoff-dependent association requires confirmation using continuous length-of-stay outcomes and prespecified thresholds in larger, multicenter cohorts.